Enalapril (Monograph)

Brand name: Vasotec
Drug class: Angiotensin-Converting Enzyme Inhibitors
- ACE Inhibitors
VA class: CV800
Chemical name: (S)-1-[N-[1-(Ethoxycarbonyl)-3-phenylpropyl]-l-alanyl]-l-proline(Z)-2-butenedioate (1:1)
Molecular formula: C₂₀H₂₈N₂O₅•C₄H₄O₄C₁₈H₂₄N₂O₅
CAS number: 75847-73-3

Enalaprilat/Enalapril Maleate is also contained as an ingredient in the following combinations:
Enalapril Maleate and Hydrochlorothiazide

Medically reviewed by Drugs.com on Oct 28, 2024. Written by ASHP.

Warning

May cause fetal and neonatal morbidity and mortality if used during pregnancy.¹ ²⁴⁵ ²⁵⁴ ²⁶³ ²⁷⁶ ²⁷⁷ ²⁹⁶ ²⁹⁷ ³⁰³ ³⁰⁵ ⁴⁵³ ⁴⁵⁴ See Fetal/Neonatal Morbidity and Mortality under Cautions.
If pregnancy is detected, discontinue as soon as possible.¹ ²⁵⁴ ²⁷⁷ ²⁹⁶ ⁴⁵⁴

Introduction

Nonsulfhydryl ACE inhibitor.¹ ² ³ ⁴ ⁵ ⁶ ⁷ ⁸ ⁹ ¹⁰ ²⁷⁷

Uses for Enalapril

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).¹ ² ⁴ ⁵ ⁹ ⁵⁴ ¹¹⁰ ¹¹⁶ ¹¹⁹ ¹²⁰ ¹²² ¹²³ ¹²⁴ ¹²⁷ ¹²⁸ ¹²⁹ ¹³⁰ ¹³¹ ¹⁴⁰ ¹⁴² ¹⁴³ ¹⁴⁴ ¹⁵⁵ ¹⁸⁶ ²⁰³ ²²⁰ ¹²⁰⁰ May use enalaprilat when oral therapy is not practical.²⁷⁷ ²⁸⁵ ²⁸⁶

ACE inhibitors are recommended as one of several preferred agents for the initial management of hypertension according to current evidence-based hypertension guidelines; other preferred options include angiotensin II receptor antagonists, calcium-channel blockers, and thiazide diuretics.⁵⁰¹ ⁵⁰² ⁵⁰³ ⁵⁰⁴ ¹²⁰⁰ While there may be individual differences with respect to recommendations for initial drug selection and use in specific patient populations, current evidence indicates that these antihypertensive drug classes all generally produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.⁵⁰¹ ⁵⁰² ⁵⁰⁴

Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).⁵⁰¹ ⁵⁰² ⁵⁰³ ⁵⁰⁴ ⁵¹⁵ ¹²⁰⁰ ¹²⁰¹

A 2017 ACC/AHA multidisciplinary hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension.¹²⁰⁰ (See Table 1.)

Source: Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-115.

Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).

Table 1. ACC/AHA BP Classification in Adults1200
Category	SBP (mm Hg)		DBP (mm Hg)
Normal	<120	and	<80
Elevated	120–129	and	<80
Hypertension, Stage 1	130–139	or	80–89
Hypertension, Stage 2	≥140	or	≥90

The goal of hypertension management and prevention is to achieve and maintain optimal control of BP.¹²⁰⁰ However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.⁵⁰¹ ⁵⁰³ ⁵⁰⁴ ⁵⁰⁵ ⁵⁰⁶ ⁵⁰⁷ ⁵⁰⁸ ⁵¹⁵ ⁵²³ ⁵²⁶ ⁵³⁰ ¹²⁰⁰ ¹²⁰¹ ¹²⁰⁷ ¹²⁰⁹ ¹²²² ¹²²³ ¹²²⁹

The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BP to achieve with drug therapy and/or nonpharmacologic intervention) of <130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk.¹²⁰⁰ In addition, an SBP goal of <130 mm Hg generally is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg.¹²⁰⁰ These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.¹²⁰⁰ ¹²⁰² ¹²¹⁰

Other hypertension guidelines generally have based target BP goals on age and comorbidities.⁵⁰¹ ⁵⁰⁴ ⁵³⁶ Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk and have used higher BP thresholds and target BPs in elderly patients compared with⁵⁰¹ ⁵⁰⁴ ⁵³⁶ those recommended by the 2017 ACC/AHA hypertension guideline.¹²⁰⁰

Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the current ACC/AHA hypertension guideline and potential harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.¹²²² ¹²²³ ¹²²⁴ ¹²²⁹

Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient’s BP treatment goal.¹²⁰⁰ ¹²²⁰

For decisions regarding when to initiate drug therapy (BP threshold), the current ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors.¹²⁰⁰ ¹²⁰⁷ ASCVD risk assessment recommended by ACC/AHA for all adults with hypertension.¹²⁰⁰

ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥ 90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).¹²⁰⁰

For secondary prevention in adults with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommend initiation of antihypertensive drug therapy at an average SBP ≥130 mm Hg or an average DBP ≥80 mm Hg.¹²⁰⁰

Adults with hypertension and diabetes mellitus, chronic kidney disease (CKD), or age ≥65 years of age are assumed to be at high risk for cardiovascular disease; ACC/AHA state that such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg.¹²⁰⁰

Individualize drug therapy in patients with hypertension and underlying cardiovascular or other risk factors.⁵⁰² ¹²⁰⁰

In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP.¹²⁰⁰ Initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes recommended in patients with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.¹²⁰⁰

Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to ACE inhibitors.⁴¹⁹ ⁴²⁰ ⁴²² ⁵⁰¹ ⁵⁰⁴ ¹²⁰⁰ However, the combination of an ACE inhibitor or an angiotensin II receptor antagonist with a calcium-channel blocker or thiazide diuretic produces similar BP lowering in black patients as in other racial groups.¹²⁰⁰

ACE inhibitors may be preferred in hypertensive patients with heart failure, ischemic heart disease, diabetes mellitus, CKD, or cerebrovascular disease or post-MI.⁵⁰¹ ⁵⁰² ⁵⁰⁴ ⁵²³ ⁵²⁴ ⁵²⁵ ⁵²⁶ ⁵²⁷ ⁵³⁴ ⁵³⁵ ⁵³⁶ ⁵⁴³ ¹²⁰⁰ ¹²¹⁴ ¹²¹⁵

Enalaprilat has been used effectively to control BP in adults with severe hypertension or hypertensive emergencies^{† [off-label]}.²⁸⁷ ²⁸⁸ ²⁸⁹ ²⁹⁰ ¹²⁰⁰ However, for treatment of hypertensive emergencies, some clinicians prefer short-acting antihypertensive agents administered by continuous IV infusion for greater ease in titrating dosage to promptly but gradually reduce BP.⁵⁰² ⁵⁴² ¹²⁰⁰

Heart Failure

Management of heart failure, usually in conjunction with other agents such as cardiac glycosides, diuretics, and β-adrenergic blocking agents (β-blockers).¹ ⁴ ⁴² ⁴⁴ ⁵⁷ ⁶¹ ⁶³ ⁶⁴ ¹⁴⁶ ¹⁴⁷ ¹⁴⁸ ¹⁵⁰ ¹⁵¹ ¹⁵² ¹⁵³ ¹⁵⁸ ¹⁵⁹ ²²⁵ ²⁴⁵ ²⁶⁰ ⁵²⁴ ⁷⁰⁰

Some evidence indicates that therapy with an ACE inhibitor may be less effective than angiotensin receptor-neprilysin inhibitor (ARNI) therapy (e.g., sacubitril/valsartan) in reducing cardiovascular death and heart failure-related hospitalization.⁷⁰⁰ ⁷⁰²

ACCF, AHA, and the Heart Failure Society of America (HFSA) recommend that patients with chronic symptomatic heart failure and reduced left ventricular ejection fraction (LVEF) (NYHA class II or III) who are able to tolerate an ACE inhibitor or angiotensin II receptor antagonist be switched to therapy containing an ARNI to further reduce morbidity and mortality.⁷⁰⁰

Asymptomatic Left Ventricular Dysfunction

Treatment of clinically stable asymptomatic patients with left ventricular dysfunction (ejection fraction ≤35%) to improve survival and to reduce the incidence of overt heart failure and subsequent hospitalizations for heart failure.¹ ²⁹⁵ ²⁹⁸ ³⁶⁰ ⁵²⁴ ⁷⁰⁴ ⁷⁰⁵

Left Ventricular Dysfunction After Acute MI

ACE inhibitors, including enalapril and enalaprilat, have been used to reduce mortality and prevent the development of left ventricular dilatation and dysfunction following acute MI^{† [off-label]}.²⁹⁹ ³⁰⁰ ³⁰⁷ ³⁰⁸ ³⁰⁹ ³¹⁰ ³¹¹ ⁵²⁴

Expert guidelines recommend initiation of an oral ACE inhibitor within the first 24 hours of acute MI in patients with an anterior infarct, heart failure, or ejection fraction ≤40% who do not have any contraindications (e.g., hypotension, shock, renal dysfunction).⁵²⁷ Use with caution (and with gradual upward titration) during initial postinfarction period because of the possibility of hypotension or renal dysfunction.⁵²⁷ ¹¹⁰⁰

Continue therapy indefinitely in patients with left ventricular dysfunction or other compelling indications (e.g., hypertension, diabetes mellitus, CKD).⁵²⁵ ¹¹⁰⁰

Diabetic Nephropathy

A recommended agent in the management of patients with diabetes mellitus and persistent albuminuria^{† [off-label]} who have modestly elevated (30–300 mg/24 hours) or higher (>300 mg/24 hours) levels of urinary albumin excretion; slows rate of progression of renal disease in such patients.²⁵ ⁵³ ⁵⁴ ⁵⁵ ⁵⁶ ⁵⁷ ⁵³⁵ ⁵³⁶ ¹²³²

Enalapril Dosage and Administration

General

BP Monitoring and Treatment Goals

Monitor BP regularly (i.e., monthly) during therapy and adjust dosage of the antihypertensive drug until BP controlled.¹²⁰⁰
If unacceptable adverse effects occur, discontinue drug and initiate another antihypertensive agent from a different pharmacologic class.¹²¹⁶
If adequate BP response not achieved with a single antihypertensive agent, either increase dosage of single drug or add a second drug with demonstrated benefit and preferably a complementary mechanism of action (e.g., calcium-channel blocker, thiazide diuretic).¹²⁰⁰ ¹²¹⁶ Many patients will require at least 2 drugs from different pharmacologic classes to achieve BP goal; if goal BP still not achieved, add a third drug.¹²⁰⁰ ¹²¹⁶ ¹²²⁰

Administration

Administer enalapril orally once or twice daily; administer enalaprilat every 6 hours by slow IV infusion.¹ ²⁷⁷ Do not administer enalaprilat by other parenteral routes.²⁷⁷

Oral Administration

Administer enalapril orally without regard to meals.¹ ² ³ ⁴ ⁵ ⁶ ⁷ ⁸ ⁹ ¹⁰ ⁹¹ ³⁵⁰ ³⁷¹ Administer enalapril as extemporaneously prepared oral suspension in patients unable to swallow tablets.¹

Reconstitution

Preparation of extemporaneous suspension containing enalapril maleate 1 mg/mL: Add 50 mL of sodium citrate dihydrate (Bicitra) to a polyethylene terephthalate (PET) bottle containing ten 20-mg tablets of enalapril maleate; shake contents for ≥2 minutes.¹ Allow concentrated suspension to stand for 60 minutes following reconstitution, then shake for an additional minute.¹ Dilute concentrated suspension with 150 mL of syrup (Ora-Sweet SF); shake container to disperse ingredients.¹ ⁴⁰⁸ Shake suspension before dispensing each dose.¹

IV Administration

Administer enalaprilat by slow IV infusion as undiluted or diluted solution.²⁷⁷

Dilution

Can dilute enalaprilat injection with up to 50 mL of compatible IV infusion solution.²⁷⁷

For solution and drug compatibility information, see Compatibility under Stability.

Rate of Administration

Infuse dose over ≥5 minutes.²⁷⁷ In patients at risk of excessive hypotension, infusion of dose over up to 1 hour is preferred.^d

Dosage

Available as enalapril maleate (oral tablets); dosage expressed in terms of the salt.¹ Also available as enalaprilat (IV injection); dosage expressed in terms of the base.^d

Dosage of enalapril and enalaprilat are not identical; caution when converting from oral to IV therapy or vice versa.²⁷⁷

May minimize risk of hypotension in patients currently receiving diuretic therapy by discontinuing the diuretic, reducing diuretic dosage, or cautiously increasing salt intake prior to initiating enalapril maleate or enalaprilat.⁶⁰⁰ ⁶⁰¹ (See Hypotension under Cautions.) For information on initiation of oral enalapril maleate or IV enalaprilat when diuretic therapy is not withheld, see the individual dosage sections in Dosage and Administration.

Pediatric Patients

Hypertension

Oral

Children 1 month to 16 years of age: Initially, enalapril maleate 0.08 mg/kg (up to 5 mg) once daily.¹ ¹¹⁵⁰ Some experts state dose may be administered as a single dose or in 2 divided doses daily.¹¹⁵⁰

Initiate drug at the low end of the dosage range per some experts; may increase dosage every 2–4 weeks until BP controlled, maximum dosage (0.58 mg/kg, up to 40 mg daily)¹ reached, or adverse effects occur.¹¹⁵⁰

Adults

Hypertension

Enalapril Therapy

Oral

Manufacturer recommends initial dosage of 5 mg daily in patients not currently receiving a diuretic.⁶⁰⁰ Adjust dosage at 2- to 4-week intervals to achieve BP control.¹¹ ²³¹

In patients currently receiving diuretic therapy, discontinue diuretic, if possible, 2–3 days before initiating enalapril.¹ ⁶ ²³⁶ ²³⁹ May cautiously resume diuretic therapy if BP not controlled adequately with enalapril alone.¹ ² ¹¹⁰ ¹¹⁶ ¹¹⁹ ¹²⁰ ¹²² ¹²³ ¹²⁴ ¹²⁷ ¹²⁸ ¹²⁹ ¹³⁰ ¹⁴⁰ ¹⁴² ¹⁴³ ²⁰³ ²²⁰ If diuretic cannot be discontinued, give initial enalapril maleate dose of 2.5 mg under close medical supervision (observe patient for ≥2 hours and until BP has stabilized for at least an additional hour).⁶⁰⁰

When switching from IV enalaprilat to oral enalapril, initiate enalapril maleate at 5 mg once daily as monotherapy.²⁷⁷ If used with a diuretic, initiate enalapril maleate at 2.5 mg once daily (in patients who responded to enalaprilat 0.625 mg every 6 hours).²⁷⁷ Adjust dosage as necessary.²⁷⁷

Usual maintenance dosage: Manufacturer states 10–40 mg daily, given in 1 dose or 2 divided doses.¹ Some experts state 5–40 mg daily, given in 1 dose or 2 divided doses.¹²⁰⁰

If effectiveness diminishes toward end of dosing interval in patients treated once daily, consider increasing dosage or administering drug in 2 divided doses.¹ ¹³

Enalapril/Hydrochlorothiazide Fixed-combination Therapy

Oral

Manufacturer states fixed-combination preparation should not be used for initial antihypertensive therapy.²⁵⁴ ³⁴⁸

If BP is not adequately controlled by monotherapy with either enalapril or hydrochlorothiazide, or if stable dosages of these drugs have been achieved,²⁵⁴ ³⁴⁸ can switch to the fixed-combination preparation containing enalapril maleate 5 mg and hydrochlorothiazide 12.5 mg or, alternatively, enalapril maleate 10 mg and hydrochlorothiazide 25 mg.²⁵⁴

Adjust dosage of either or both drugs according to patient’s response.²⁵⁴ ³⁴⁸

Enalaprilat Therapy

Initially, enalaprilat 1.25 mg every 6 hours in patients not receiving a diuretic or in those converting from enalapril monotherapy.²⁷⁷

In patients receiving a diuretic, enalaprilat 0.625 mg initially.²⁷⁷ If BP response after 1 hour is inadequate, administer another dose of 0.625 mg.²⁷⁷ May administer additional doses of 1.25 mg at 6-hour intervals.²⁷⁷

In patients at risk of marked hypotension (see Hypotension under Cautions), ≤0.625 mg of enalaprilat initially, given by slow IV infusion (over ≥5 minutes, preferably up to 1 hour) under very close medical supervision.^d

Hypertensive Emergency† [off-label]

IV

Enalaprilat: 1.25–5 mg, repeated every 6 hours as necessary, has been recommended.¹²⁰⁰

Without compelling condition: Initial goal is to reduce SBP by no more than 25% within 1 hour, followed by further reduction if stable toward 160/100 to 110 mm Hg within the next 2–6 hours, avoiding excessive declines in BP that could precipitate renal, cerebral, or coronary ischemia.¹²⁰⁰ If patient is stable, can further reduce BP toward normal in the next 24–48 hours.¹²⁰⁰

Heart Failure

Oral

Usual initial enalapril maleate dosage: 2.5 mg twice daily in patients with normal renal function and serum sodium concentration.¹ ⁵²⁴

Usual maintenance dosage: 5–40 mg daily, given in 2 divided doses.⁴² ⁴⁴ ⁵⁷ ⁶¹ ⁶³ ⁶⁴ ¹⁴⁶ ¹⁴⁷ ¹⁴⁸ ¹⁵⁰ ¹⁵¹ ¹⁵² ¹⁵³ ¹⁵⁴ ²⁴⁵ ⁵²⁴

Following initial dose, monitor closely for ≥2 hours and until BP has stabilized for at least an additional hour.²⁴⁵ To minimize risk of hypotension, reduce diuretic dosage, if possible, prior to initiating therapy.¹ Adjust dosage gradually as tolerated to prespecified target (≥20 mg of enalapril maleate daily) or maximum tolerated dosage.⁵²⁴

In patients with hyponatremia (serum sodium concentration <130 mEq/L), manufacturer recommends initial enalapril maleate dosage of 2.5 mg daily under close monitoring.¹ Increase dosage at intervals of ≥4 days, to 2.5 mg twice daily, then 5 mg twice daily, and then higher, provided excessive hypotension or deterioration of renal function is not present at the time of intended dosage adjustment; dosage should not exceed 40 mg daily.¹

Asymptomatic Left Ventricular Dysfunction

Oral

Initially, enalapril maleate 2.5 mg twice daily.¹ Titrate upward as tolerated to target dosage of 20 mg daily, given in divided doses.¹ Following initial dose, monitor closely for ≥2 hours and until BP has stabilized for at least an additional hour.¹ To minimize risk of hypotension, reduce diuretic dosage, if possible, prior to initiating therapy.¹

Prescribing Limits

Pediatric Patients

Hypertension

Oral

Maximum 0.58 mg/kg or 40 mg of enalapril maleate daily.¹

Adults

Hypertension

Oral

Dosage of enalapril/hydrochlorothiazide fixed combination generally should not exceed enalapril maleate 20 mg and hydrochlorothiazide 50 mg daily.²⁵⁴ ³²³ ³⁴⁸

IV

Enalaprilat dosages up to 5 mg every 6 hours were well tolerated for up to 36 hours in controlled clinical studies.²⁷⁷ Insufficient experience with dosages >20 mg daily.²⁷⁷

Enalaprilat usually is not administered for >48 hours, but has been administered for as long as 7 days.²⁷⁷

Heart Failure

Oral

Maximum 40 mg of enalapril maleate daily, given in 2 divided doses.¹ ²⁴⁵ ⁵²⁴

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.¹

Renal Impairment

Hypertension

Enalapril Therapy

Oral

Patients with Cl_cr >30 mL/minute: Manufacturer states that no adjustment of enalapril maleate dosage is required.¹

Adults with Cl_cr ≤30 mL/minute or S_cr ≥3 mg/dL: Manufacturer recommends initial enalapril maleate dosage of 2.5 mg once daily; titrate until BP is controlled or to maximum of 40 mg daily.¹ When switching from IV enalaprilat, initiate oral therapy at 2.5 mg once daily;²⁷⁷ adjust dosage according to patient’s BP response.²⁷⁷

Manufacturer does not recommend use of enalapril in pediatric patients with Cl_cr <30 mL/minute per 1.73 m².¹

Some clinicians recommend dosage of 75–100% of usual enalapril dosage in patients with Cl_cr of 10–50 mL/minute and dosage of 50% of usual enalapril dosage in those with Cl_cr <10 mL/minute.²⁶⁴

Hemodialysis patients: Enalapril maleate 2.5 mg on dialysis days; on days between dialysis, adjust dosage according to BP response.¹

Enalapril/Hydrochlorothiazide Fixed-combination Therapy

Oral

Not recommended in patients with severe renal impairment.²⁵⁴ No dosage adjustment required if Cl_cr >30 mL/minute.⁴⁵⁵

Enalaprilat Therapy

Adults with Cl_cr >30 mL/minute: No adjustment of enalaprilat dosage required.²⁷⁷

Adults with Cl_cr ≤30 mL/minute or S_cr ≥3 mg/dL: Enalaprilat 0.625 mg initially.²⁷⁷ If BP response after 1 hour is inadequate, administer another dose of 0.625 mg.²⁷⁷ May administer additional doses of 1.25 mg at 6-hour intervals.²⁷⁷

Hemodialysis patients: Enalaprilat 0.625 mg every 6 hours.²⁷⁷

Heart Failure

Oral

Patients with S_cr >1.6 mg/dL: Enalapril maleate 2.5 mg daily initially under close monitoring.¹ Increase dosage at intervals of ≥4 days, to 2.5 mg twice daily, then 5 mg twice daily, and then higher, provided excessive hypotension or deterioration of renal function is not present at the time of intended dosage adjustment; do not exceed 40 mg daily.¹

Geriatric Patients

Hypertension

Initiate therapy with enalapril/hydrochlorothiazide fixed combination at lower end of usual range.²⁵⁴ ³⁴⁸

Cautions for Enalapril

Contraindications

Known hypersensitivity (e.g. history of angioedema) to enalapril, enalaprilat, or another ACE inhibitor or any ingredient in the formulation.¹ ^d
History of hereditary or idiopathic angioedema.¹ ^d

Warnings/Precautions

Warnings

Hypotension

Risk of marked hypotension, sometimes associated with oliguria, azotemia, and, rarely, death, in volume- and/or salt-depleted patients (e.g., those with heart failure with or without associated renal insufficiency, hyponatremia, high-dose or recent intensive diuretic therapy or recent increase in diuretic dose, dialysis).¹ ⁶ ⁵⁷ ¹²² ¹⁵² ¹⁶³ ¹⁶⁴ ¹⁶⁵ ²³⁹ ²⁴⁵ ²⁶⁰ ⁶⁰⁰ Severe hypotension reported in such patients following IV enalaprilat doses as low as 0.2 mg.^d Severe hypotension may result in MI or stroke in patients with ischemic cardiovascular or cerebrovascular disease.¹

Hypotension may occur in patients undergoing surgery or during anesthesia with agents that produce hypotension; recommended treatment is fluid volume expansion.¹

To minimize potential for hypotension, consider recent antihypertensive therapy, extent of BP elevation, sodium intake, fluid status, and other clinical conditions.¹ ⁵ ⁶ ²³⁹ May minimize potential for hypotension in patients at risk for excessive hypotension by withholding diuretic therapy (except in patients with heart failure), reducing diuretic dosage, and/or cautiously increasing sodium intake prior to initiation of enalapril.⁶ ²³⁶ ²³⁹ ⁶⁰⁰ (See Dosage under Dosage and Administration.)

Initiate therapy in patients at risk for excessive hypotension under close medical supervision; monitor closely for first 2 weeks following initiation of enalapril or any increase in enalapril or diuretic dosage.²⁴⁵ ²⁶⁰ ⁶⁰⁰ ^b

If excessive hypotension occurs, immediately place patient in supine position and, if necessary, administer IV infusion of 0.9% sodium chloride.¹ ⁴ ⁵ ¹⁸³ ²⁴⁵ ²⁵⁴ Enalapril therapy usually can be continued following restoration of volume and BP.¹ ²⁴⁵ If symptomatic hypotension develops, dosage reduction or discontinuance of enalapril or diuretic may be necessary.¹ ²⁴⁵

Hematologic Effects

Neutropenia and agranulocytosis reported with captopril;¹ ²⁰⁸ ²⁰⁹ ²¹⁰ risk of neutropenia appears to depend principally on presence of renal impairment and presence of collagen vascular disease (e.g., systemic lupus erythematosus, scleroderma).¹ ²²³ ²²⁶ Several cases of neutropenia or agranulocytosis reported with enalapril; causal relationship could not be excluded.¹ ⁶ ¹⁷⁵

Consider monitoring leukocytes in patients with collagen vascular disease, especially if renal impairment exists.¹

Fetal/Neonatal Morbidity and Mortality

Possible fetal and neonatal morbidity and mortality when ACE inhibitors used during pregnancy.¹ ⁴⁵³ ⁴⁵⁴ (See Boxed Warning.) Such potential risks occur throughout pregnancy, especially during the second and third trimesters.⁴⁵⁴

Also may increase the risk of major congenital malformations when administered during the first trimester of pregnancy.⁴⁵³ ⁴⁵⁴

Discontinue as soon as possible when pregnancy is detected, unless continued use is considered lifesaving.⁴⁵⁴ Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy.²⁹⁷

Hepatic Effects

Clinical syndrome that usually is manifested initially by cholestatic jaundice and may progress to fulminant hepatic necrosis (occasionally fatal) reported rarely with ACE inhibitors.¹

If jaundice or marked elevation of liver enzymes occurs, discontinue drug and monitor patient.¹

Sensitivity Reactions

Anaphylactoid reactions and/or angioedema possible; if associated with laryngeal edema, may be fatal.¹ ²⁴⁵ ²⁵⁴ Immediate medical intervention (e.g., epinephrine) for involvement of tongue, glottis, or larynx.¹ ²⁴⁵ ²⁵⁴ Intestinal angioedema possible; consider in differential diagnosis of patients who develop abdominal pain.⁴⁵²

Anaphylactoid reactions reported in patients receiving ACE inhibitors while undergoing LDL apheresis with dextran sulfate absorption¹ ²⁵⁴ ²⁷⁷ ³¹⁹ ³²⁰ ³²¹ or following initiation of hemodialysis that utilized high-flux membrane.¹ ²⁵⁴ ²⁷⁷ ³⁰² ³⁰⁴ ³⁰⁶

Life-threatening anaphylactoid reactions reported in at least 2 patients receiving ACE inhibitors while undergoing desensitization treatment with hymenoptera venom.¹ ²⁵⁴ ²⁷⁷

Contraindicated in patients with a history of angioedema associated with ACE inhibitors and in patients with hereditary or idiopathic angioedema.¹ ⁴⁰⁷

General Precautions

Renal Effects

Transient increases in BUN and S_cr possible, especially in patients with preexisting renal impairment or those receiving concomitant diuretic therapy.¹ ⁴ ²³⁴ ²⁵⁴ ²⁶² Possible increases in BUN and S_cr in patients with unilateral or bilateral renal-artery stenosis;¹ ⁶ ⁵⁰ ¹¹⁶ ¹⁶¹ ¹⁶⁷ ¹⁶⁹ ²³¹ ²³⁴ ³⁷⁹ generally reversible following discontinuance of ACE inhibitor and/or diuretic.¹ ¹⁶¹ ¹⁶⁷ ²³⁴ ³⁷⁹

Possible oliguria, progressive azotemia, and, rarely, acute renal failure and/or death in patients with severe heart failure.¹ ¹⁵² ²⁴⁵ ²⁵⁴ ²⁶²

Closely monitor renal function following initiation of therapy in patients with heart failure or unilateral or bilateral renal-artery stenosis.¹ ²⁴⁵ Some patients may require dosage reduction or discontinuance of ACE inhibitor or diuretic and/or adequate sodium repletion.¹ ⁴² ¹⁵² ¹⁶⁶ ²³⁶ ²³⁹ ²⁶⁰ ²⁶²

Hyperkalemia

Possible hyperkalemia, especially in patients with renal impairment or diabetes mellitus and those receiving drugs that can increase serum potassium concentrations (e.g., potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes).¹ ⁶⁴ ¹⁵² ¹⁷² ¹⁷⁴ ²³⁵ ²³⁹ ²⁴⁵ ²⁵⁴ (See Specific Drugs under Interactions.)

Monitor serum potassium concentration carefully in these patients.¹ ²³⁵ ²⁴⁵

Cough

Persistent and nonproductive cough;¹ ²⁷⁷ resolves after drug discontinuance.¹ ¹⁷³ ²⁴¹ ²⁵² ²⁵⁶ ²⁵⁸ ²⁷⁷

Valvular Stenosis

Use with caution in patients with obstruction in the outflow tract of the left ventricle (e.g., aortic stenosis, hypertrophic cardiomyopathy).¹

Use of Fixed Combinations

When used in fixed combination with hydrochlorothiazide, consider the cautions, precautions, and contraindications associated with hydrochlorothiazide.^e

Specific Populations

Pregnancy

Enalapril/enalaprilat: Category C (1st trimester); Category D (2nd and 3rd trimesters).¹ ^d (See Boxed Warning.)

Lactation

Distributed into milk; discontinue nursing or the drug.¹ ²⁵⁴

Pediatric Use

Antihypertensive effects of oral enalapril established in hypertensive pediatric patients 1 month to 16 years of age;¹ adverse effect profile of enalapril similar to that in adults.¹ Enalapril is not recommended for neonates or for pediatric patients with Cl_cr <30 mL/minute per 1.73 m².¹

Safety and efficacy of IV enalaprilat or of oral enalapril in fixed combination with felodipine or hydrochlorothiazide not established in children.²⁴⁵ ²⁵⁴ ^e

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently to enalapril in fixed combination with hydrochlorothiazide than younger adults; select dosage with caution.⁴⁵⁵ (See Geriatric Patients under Dosage and Administration.)

Renal Impairment

Systemic exposure to enalaprilat may be increased.¹ ⁸⁹ ⁹³ ⁹⁴ ⁹⁶ ²⁸¹ (See Absorption: Special Populations, under Pharmacokinetics.) Initial dosage adjustment may be necessary depending on degree of renal impairment.¹ ²⁶⁴ ²⁷⁷ (See Renal Impairment under Dosage and Administration.)

Deterioration of renal function may occur.¹ (See Renal Effects under Cautions.)

Enalapril/hydrochlorothiazide fixed combinations are not recommended in patients with severe renal impairment (Cl_cr ≤30 mL/minute or S_cr >3 mg/dL).^e

Black Patients

BP reduction achieved with ACE inhibitor may be smaller in black patients compared with nonblack patients.¹ ² ⁹ ⁷⁸ ¹²¹ ²⁶⁹ ²⁷⁰ ²⁷¹ ⁴¹⁹ ⁴²⁰ ⁴⁵⁰ ⁴⁵¹ (See Hypertension under Uses.)

Higher incidence of angioedema reported with ACE inhibitors in black patients compared with other races.¹ ³⁴⁸ ³⁴⁹ ⁴²⁰

Common Adverse Effects

Enalapril in patients with hypertension: Headache, fatigue, dizziness.¹

Enalapril in patients with heart failure: Orthostatic effects, syncope, chest pain, hypotension, diarrhea, dizziness, cough.¹

Enalaprilat: Hypotension.^d

Drug Interactions

Specific Drugs

Drug	Interaction	Comments
Antidiabetic agents	Possible hypoglycemia in diabetic patients¹⁷⁶	Consider risk of hypoglycemia if used concomitantly¹⁷⁶
Diuretics	Increased hypotensive effect¹ ⁴ ¹²⁰ ¹²² ¹²⁸ ¹²⁹ ¹³¹ ²⁵⁴	If possible, discontinue diuretic before initiating enalapril or enalaprilat¹ ⁶ ²³⁶ ²³⁹ (see Dosage under Dosage and Administration)
Diuretics, potassium-sparing (amiloride, spironolactone, triamterene)	Enhanced hyperkalemic effect¹ ²⁴⁵	Use with caution; monitor serum potassium concentrations frequently¹ ²⁴⁵
Hypotensive agents (e.g., nitrates, certain anesthetics)	Increased hypotensive effect¹ ⁵
Lithium	Increased serum lithium concentrations; possible toxicity¹ ⁷⁸ ¹⁸⁰	Use with caution; monitor serum lithium concentrations frequently¹
NSAIAs	Possible reduced BP response to enalapril;³²² ³²³ ³²⁴ ³²⁵ ³²⁶ ³²⁷ ³²⁸ ³²⁹ ³⁷⁰ ⁴⁰⁴ ⁷⁰⁶ potential for acute reduction of renal function;³²⁴ ³³⁰ possible attenuation of hemodynamic effects in patients with heart failure³⁷⁹ ⁴⁰⁴	Monitor BP carefully and be alert for evidence of impaired renal function³²⁴
Potassium supplements or potassium-containing salt substitutes	Enhanced hyperkalemic effect¹ ²⁴⁵	Use with caution; monitor serum potassium concentrations frequently¹ ²⁴⁵

Enalapril Pharmacokinetics

Absorption

Bioavailability

Approximately 55–75% of an oral dose of enalapril is rapidly absorbed;¹ ² ⁸³ ⁸⁴ enalaprilat is poorly absorbed from GI tract.¹ ¹² ¹⁷ ⁸⁵ ⁹⁷ ¹⁸⁷

Enalapril undergoes first-pass metabolism to enalaprilat (the active moiety).¹ ² ¹⁰ ⁴⁶ ⁸³ ⁹⁵ ⁹⁷ ⁹⁹ ¹⁹⁰ Peak serum concentrations of enalapril and enalaprilat are achieved within 0.5–1.5 and 3–4.5 hours, respectively, following oral administration.¹ ² ⁴ ⁵ ¹⁰ ⁴⁶ ⁸³ ⁸⁴ ⁸⁶ ⁸⁸ ⁹¹ ²⁴⁴ ²⁸³ ²⁸⁴

Concomitant oral administration of enalapril and hydrochlorothiazide has little, if any, effect on the bioavailability of either drug in the combination.^e

Onset

Following a single oral dose of enalapril, antihypertensive effects are observed in 1 hour, with peak BP reduction at 4–8 hours.¹ ⁴³ ⁴⁶ ⁹⁰

Following IV dose of enalaprilat, hypotensive effect usually is apparent within 5–15 minutes, with maximal effect within 1–4 hours;²⁷⁷ ²⁸⁶ ²⁸⁷ ²⁸⁸ ²⁸⁹ effects of second and third doses may exceed those of first dose.²⁷⁷

Duration

Following oral administration of enalapril, hypotensive effect generally persists for 12–24 hours.¹ ⁴¹ ⁴³ ⁴⁴ ⁴⁵ ⁴⁶ ⁴⁸ ⁵⁰ ⁵⁸ ²³¹ Several weeks of therapy may be required before full effect is achieved.¹ ⁴⁶ ⁵¹ ⁶² ⁷⁹

Following IV administration of recommended doses of enalaprilat, hypotensive effect persists for approximately 6 hours.²⁷⁷ ²⁸⁶

Food

Food does not affect absorption of enalapril.¹ ⁸⁸ ⁹¹

Special Populations

In patients with impaired renal function, enalaprilat concentrations and AUCs may be increased; time to peak and steady-state serum concentration may be delayed.¹ ⁸⁹ ⁹³ ⁹⁴ ⁹⁶ ²⁸¹ Effective half-life for accumulation of enalaprilat is prolonged in patients with Cl_cr <30 mL/minute but not in those with Cl_cr of 30–60 mL/minute.¹ ⁹³ ⁹⁴

Distribution

Extent

Enalapril appears to cross the blood-brain barrier poorly, if at all; enalaprilat does not appear to distribute into the CNS.¹ ²

Enalaprilat crosses the placenta.²⁶³

Enalapril and enalaprilat are distributed into milk in trace amounts.¹ ²⁷⁷

Plasma Protein Binding

Enalaprilat: Approximately 50–60%.² ⁴ ¹⁰

Elimination

Metabolism

Metabolized in the liver, principally to an active metabolite, enalaprilat.¹ ² ¹⁰ ⁴⁶ ⁹⁵ ⁹⁷ ⁹⁹

Elimination Route

Enalapril is eliminated in urine (60–78% within 24–48 hours) as unchanged drug and enalaprilat¹ ⁴ ⁸⁴ ⁸⁷ ²⁴⁴ and also in feces (approximately 33% within 24–48 hours).¹ ² ⁴ ⁸⁴

Enalaprilat is eliminated in urine as unchanged drug.^d

Enalaprilat is removed by hemodialysis¹ ² ⁸⁹ ⁹⁴ ²⁸² and peritoneal dialysis.²⁴⁵ ²⁵⁴ ²⁶³

Half-life

Enalapril: <2 hours.⁸⁶ ¹⁰⁰ ¹⁰¹ ²⁸³ ²⁸⁴

Enalaprilat: 11 hours.¹ ² ⁸⁷

Special Populations

In patients with hepatic impairment, elimination of enalaprilat may be prolonged.²⁸³ ²⁸⁴ Hydrolysis of enalapril to enalaprilat may be delayed⁸⁸ ⁹⁵ ²⁸³ and/or impaired²⁸³ in patients with severe hepatic impairment.⁸⁸ ⁹⁵ ²⁸³

In patients with GFR ≤30 mL/minute, half-life of enalaprilat is prolonged.^d

In patients with heart failure, enalapril half-life may be increased and enalaprilat elimination prolonged.¹⁰⁰

Stability

Storage

Oral

Extemporaneous Suspension

1-mg/mL preparation of enalapril maleate tablets in syrup (Ora-Sweet SF) and sodium citrate dihydrate (Bicitra) (see Oral Administration under Dosage and Administration): Up to 30 days at 2–8°C.¹ ⁴⁰⁸

Tablets

Enalapril: Tight container at 25°C (may be exposed to 15–30°C); protect from moisture.¹

Enalapril/hydrochlorothiazide fixed-combination preparations: Tightly closed container at 25°C (may be exposed to 15–30°C). ⁴⁵⁵ Protect from moisture.⁴⁵⁵

Parenteral

Injection

<30°C.²⁷⁷

Compatibility

Parenteral

Solution Compatibilityd HID

Compatible
Dextran 40 10% in dextrose 5%
Dextrose 5% in Ringer’s injection, lactated
Dextrose 5% in sodium chloride 0.9%^d
Dextrose 5% in water
Hetastarch 6% in sodium chloride 0.9%
Normosol R
Sodium chloride 0.9%^d

Drug Compatibility

Admixture CompatibilityHID
Compatible
Dobutamine HCl
Dopamine HCl
Heparin sodium
Meropenem
Nitroglycerin
Potassium chloride
Sodium nitroprusside

Y-Site CompatibilityHID
Compatible
Allopurinol sodium
Amifostine
Amikacin sulfate
Aminophylline
Ampicillin sodium
Ampicillin sodium–sulbactam sodium
Aztreonam
Bivalirudin
Butorphanol tartrate
Calcium gluconate
Cefazolin sodium
Ceftaroline fosamil
Ceftazidime
Chloramphenicol sodium succinate
Cisatracurium besylate
Cladribine
Clindamycin phosphate
Co-trimoxazole
Dexmedetomidine HCl
Dextran 40
Dobutamine HCl
Docetaxel
Dopamine HCl
Doripenem
Doxorubicin HCl liposome injection
Erythromycin lactobionate
Esmolol HCl
Etoposide phosphate
Famotidine
Fenoldopam mesylate
Fentanyl citrate
Filgrastim
Ganciclovir sodium
Gemcitabine HCl
Gentamicin sulfate
Granisetron HCl
Heparin sodium
Hetastarch in lactated electrolyte injection (Hextend)
Hetastarch in sodium chloride 0.9%
Hydrocortisone sodium succinate
Labetalol HCl
Lidocaine HCl
Linezolid
Magnesium sulfate
Melphalan HCl
Meropenem
Methylprednisolone sodium succinate
Metronidazole
Morphine sulfate
Nafcillin sodium
Nicardipine HCl
Oxaliplatin
Pemetrexed disodium
Penicillin G potassium
Phenobarbital sodium
Piperacillin sodium–tazobactam sodium
Potassium chloride
Potassium phosphates
Propofol
Ranitidine HCl
Remifentanil HCl
Sodium acetate
Sodium nitroprusside
Teniposide
Thiotepa
Tobramycin sulfate
Vancomycin HCl
Vinorelbine tartrate
Incompatible
Amphotericin B
Amphotericin B cholesteryl sulfate complex
Nesiritide
Phenytoin sodium

Actions

Enalapril is a prodrug; has little pharmacologic activity until hydrolyzed to enalaprilat.¹ ² ⁴ ⁵ ⁶ ⁷ ⁸ ¹⁶ ¹⁷ ²⁰
Suppresses the renin-angiotensin-aldosterone system.¹ ² ⁴ ⁵ ¹⁰

Advice to Patients

Risk of angioedema, anaphylactoid reactions, or other sensitivity reactions.¹ Importance of reporting sensitivity reactions (e.g., edema of the face, eyes, lips, tongue, or extremities; hoarseness; swallowing or breathing with difficulty) immediately to clinician and of discontinuing the drug.¹
Importance of reporting signs of infection (e.g., sore throat, fever).¹
Risk of hypotension.¹ Importance of informing clinicians promptly if lightheadedness or fainting occurs.¹
Importance of adequate fluid intake; risk of volume depletion with excessive perspiration, dehydration, vomiting, or diarrhea.¹
Risks of use during pregnancy.¹ ⁴⁵³ ⁴⁵⁴ (See Boxed Warning.)
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (including salt substitutes containing potassium).¹
Importance of women informing their clinicians if they are or plan to become pregnant or plan to breast-feed.¹
Importance of advising patients of other important precautionary information.¹ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Enalaprilat
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection, for IV use only	equivalent to 1.25 mg of anhydrous enalaprilat per mL*	Enalaprilat Injection

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Enalapril Maleate
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	2.5 mg*	Vasotec (scored)	Valeant
		5 mg*	Vasotec (scored)	Valeant
		10 mg*	Vasotec (scored)	Valeant
		20 mg*	Vasotec (scored)	Valeant

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Enalapril Maleate and Hydrochlorothiazide
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	5 mg Enalapril Maleate and Hydrochlorothiazide 12.5 mg*	Enalapril Maleate and Hydrochlorothiazide Tablets
		10 mg Enalapril Maleate and Hydrochlorothiazide 25 mg*	Enalapril Maleate and Hydrochlorothiazide Tablets
			Vaseretic	Valeant

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Biovail Pharmaceuticals, Inc. Vasotec (enalapril maleate) tablets prescribing information. Morrisville, NC; 2002 Aug.

2. Merck Sharp & Dohme. Vasotec (enalapril maleate) formulary information monograph. West Point, PA; 1986.

3. Windholz M, ed. The Merck index. 10th ed. Rahway, NJ: Merck & Co, Inc; 1983: APP-1-2.

4. Todd PA, Heel RC. Enalapril: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension and congestive heart failure. Drugs. 1986; 31:198-248. https://pubmed.ncbi.nlm.nih.gov/3011386

5. Vlasses PH, Larijani GE, Conner DP et al. Enalapril, a nonsulfhydryl angiotensin-converting enzyme inhibitor. Clin Pharm. 1985; 4:27-40. https://pubmed.ncbi.nlm.nih.gov/2982541

6. Anon. Enalapril for hypertension. Med Lett Drugs Ther. 1986; 28:53-4. https://pubmed.ncbi.nlm.nih.gov/3010064

7. Cleary JD, Taylor JW. Enalapril: a new angiotensin converting enzyme inhibitor. Drug Intell Clin Pharm. 1986; 20:177-86. https://pubmed.ncbi.nlm.nih.gov/3007062

8. Gomez HJ, Cirillo VJ, Irvin JD. Enalapril: a review of human pharmacology. Drugs. 1985; 30(Suppl 1):13-24. https://pubmed.ncbi.nlm.nih.gov/2994984

9. Davies RO, Irvin JD, Kramsch DK et al. Enalapril worldwide experience. Am J Med. 1984; 77:23-35. https://pubmed.ncbi.nlm.nih.gov/6089556

10. Davies RO, Gomez HJ, Irvin JD et al. An overview of the clinical pharmacology of enalapril. Br J Clin Pharmacol. 1984; 18:215-29S. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1463526/ https://pubmed.ncbi.nlm.nih.gov/6386022

11. Riley LJ Jr, Vlasses PH, Ferguson RK. Clinical pharmacology and therapeutic applications of the new oral converting enzyme inhibitor, enalapril. Am Heart J. 1985; 109:1085-9. https://pubmed.ncbi.nlm.nih.gov/2986440

12. Sweet CS, Ulm EH. Enalapril. New Drugs Ann. 1984; 2:1-17.

13. Douglas WW. Polypeptides—angiotensin, plasma kinins, and others. In: Gilman AG, Goodman L, Rall TW et al. Goodman and Gilman’s the pharmacological basis of therapeutics. 7th ed. New York: Macmillan Publishing Company; 1985: 639-60.

14. Patchett AA, Harris E, Tristram EW et al. A new class of angiotensin-converting enzyme inhibitors. Nature. 1980; 288:280-3. https://pubmed.ncbi.nlm.nih.gov/6253826

15. Attwood MR, Francis RJ, Hassall CH et al. New potent inhibitors of angiotensin converting enzyme. FEBS Lett. 1984; 165:201-6. https://pubmed.ncbi.nlm.nih.gov/6319181

16. Chen DS, Brunner HR, Waeber B. In-vitro response of plasma angiotensin converting enzyme to precursors and active forms of converting enzyme inhibitors. Curr Ther Res. 1984; 35:253-62.

17. Gross DM, Sweet CS, Ulm EH et al. Effect of N-[(S)-1-Carboxy-3-phenylpropyl]-l-Ala-l-Pro and its ethyl ester (MK-421) on angiotensin converting enzyme in vitro and angiotensin I pressor responses in vivo. J Pharmacol Exp Ther. 1981; 216:552-7.

18. Natoff IL, Nixon JS, Francis RJ et al. Biological properties of the angiotensin-converting enzyme inhibitor cilazapril. J Cardiovasc Pharmacol. 1985; 7:69-80.

19. Ryan MJ, Boucher DM, Cohen DM et al. Antihypertensive effects of CI-907 (indolapril): a novel nonsulfhydryl angiotensin converting enzyme inhibitor. J Pharmacol Exp Ther. 1984; 228:312-8. https://pubmed.ncbi.nlm.nih.gov/6319675

20. Unger T, Schull B, Rascher W et al. Selective activation of the converting enzyme inhibitor MK 421 and comparison of its active diacid form with captopril in different tissues of the rat. Biochem Pharmacol. 1982; 31:3063-70. https://pubmed.ncbi.nlm.nih.gov/6293506

21. Nakashima N, Angus JA, Johnston CI. Comparison of angiotensin converting enzyme inhibitors captopril and MK 421-diacid in guinea pig atria. Eur J Pharmacol. 1982; 81:487-92. https://pubmed.ncbi.nlm.nih.gov/6288415

22. Reynolds CH. Kinetics of inhibition of angiotensin converting enzyme by captopril and by enalapril diacid. Biochem Pharmacol. 1984; 33:1273-6. https://pubmed.ncbi.nlm.nih.gov/6324821

23. Bünning P. Inhibition of angiotensin converting enzyme by 2-[N-[(S)-1-carboxy-3-phenylpropyl]-l-alanyl]- (1S,3S,5S)-2-azabicyclo[3.3.0]octane-3-carboxylic acid (Hoe 498 Diacid). Arzneimittelforschung. 1984; 34:1406-10. https://pubmed.ncbi.nlm.nih.gov/6097266

24. Cohen ML, Kurz K. Captopril and MK-421: stability on storage, distribution to the central nervous system, and onset of activity. Fed Proc. 1983; 42:171-5. https://pubmed.ncbi.nlm.nih.gov/6295820

25. Cohen ML, Wiley KS, Kurz KD. Effect of acute oral administration of captopril and MK-421 on vascular angiotensin converting enzyme activity in the spontaneously hypertensive rat. Life Sci. 1983; 32:565-9. https://pubmed.ncbi.nlm.nih.gov/6300600

26. Gaul SL, Martin GE, Sweet CS. Comparative effects of enalapril, enalaprilic acid and captopril in blocking angiotensin I-induced pressor and dipsogenic responses in spontaneously hypertensive rats. Clin Exp Hypertens. 1984; A6:1187-1206.

27. Unger T, Ganten D, Lang RE et al. Is tissue converting enzyme inhibition a determinant of the antihypertensive efficacy of converting enzyme inhibitors? Studies with the two different compounds, Hoe 498 and MK421, in spontaneously hypertensive rats. J Cardiovasc Pharmacol. 1984; 6:872-80. https://pubmed.ncbi.nlm.nih.gov/6209494

28. Sweet CS, Gaul SL, Reitz PM et al. Mechanism of action of enalapril in experimental hypertension and acute left ventricular failure. J Hypertens. 1983; 1(Suppl 1):53-63. https://pubmed.ncbi.nlm.nih.gov/6099380

29. Forslund T, Fyhrquist F, Gronhagen-Riska C et al. Induction of angiotensin-converting enzyme with the ACE inhibitory compound MK-421 in rat lung. Eur J Pharmacol. 1982; 80:121-5. https://pubmed.ncbi.nlm.nih.gov/6284528

30. Ulm EH, Vassil TC. Total serum angiotensin converting enzyme activity in rats and dogs after enalapril maleate (MK-421). Life Sci. 30:1225-30.

31. McCaa RE, Gillespie JB. Effects of captopril and enalapril on sodium excretion and blood pressure in sodium-deficient dogs. Fed Proc. 1984; 45:1336-41.

32. Schiffrin EL, Gutkowska J, Thibault G et al. Effect of enalapril (MK-421), an orally active angiotensin I converting enzyme inhibitor, on blood pressure, active and inactive plasma renin, urinary prostaglandin E₂, and kallikrein excretion in conscious rats. Can J Physiol Pharmacol. 1984; 62:116-23. https://pubmed.ncbi.nlm.nih.gov/6143602

33. Clauser E, Gonzalez MF, Bouhnik J et al. The effects of converting enzyme inhibitors on plasma angiotensinogen and plasma aldosterone in sodium-depleted rats. J Hypertens. 1983; 1(Suppl 1):37-40. https://pubmed.ncbi.nlm.nih.gov/6397512

34. Sweet CS, Arbegast PT, Gaul SL et al. Relationship between angiotensin I blockade and antihypertensive properties of single doses of MK-421 and captopril in spontaneous and renal hypertensive rats. Eur J Pharmacol. 1981; 76:167-76. https://pubmed.ncbi.nlm.nih.gov/6174351

35. Jackson B, Johnston CI. Angiotensin converting enzyme inhibition by MK-421: a potent long acting oral agent. Aust N Z J Med. 1982; 12:362.

36. Richer C, Doussau MP, Giudicelli JF. MK 421 and prevention of genetic hypertension development in young spontaneously hypertensive rats. Eur J Pharmacol. 1982; 79:23-9. https://pubmed.ncbi.nlm.nih.gov/6282598

37. Sweet CS, Gaul SL, Ulm EH. Converting enzyme inhibition with enalapril during chronic angiotensin II infusion in rats. Fed Proc. 1983; 42:1019.

38. Wilkes BM. Evidence for a vasodepressor effect of the angiotensin-converting enzyme inhibitor, MK421 (enalapril), independent of blockade of angiotensin II formation. J Cardiovasc Pharmacol. 1984; 6:1036-42. https://pubmed.ncbi.nlm.nih.gov/6084759

39. Baum T, Becker FT, Sybertz EJ. Attenuation of pressor responses to intracerebroventricular angiotensin I by angiotensin converting enzyme inhibitors and their effects on systemic blood pressure in conscious rats. Life Sci. 1983; 32:1297-1303. https://pubmed.ncbi.nlm.nih.gov/6300578

40. Unger T, Ganten D, Lang RE et al. Persistent tissue converting enzyme inhibition following chronic treatment with Hoe498 and MK421 in spontaneously hypertensive rats. J Cardiovasc Pharmacol. 1985; 7:36-41. https://pubmed.ncbi.nlm.nih.gov/2580148

41. de Leeuw PW, Hoogma RPLM, van Soest GAW et al. Humoral and renal effects of MK-421 (enalapril) in hypertensive subjects. J Cardiovasc Pharmacol. 1983; 5:731-6. https://pubmed.ncbi.nlm.nih.gov/6195458

42. Cody RJ. Clinical and hemodynamic experience with enalapril in congestive heart failure. Am J Cardiol. 1985; 55:36-40.

43. Ferguson RK, Vlasses PH, Swanson BN et al. Effect of enalapril, a new converting enzyme inhibitor, in hypertension. Clin Pharmacol Ther. 1982; 32:48-53. https://pubmed.ncbi.nlm.nih.gov/6282527

44. Kjekshus IK, Soyland E, Dickstein K et al. Acute and long-term response to enalapril in congestive failure. Br J Clin Pharmacol. 1984; 18:169-74S. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1463509/ https://pubmed.ncbi.nlm.nih.gov/6487456

45. Hodsman GP, Zabludowski JR, Zoccali C et al. Enalapril (MK421) and its lysine analogue (MK521): a comparison of acute and chronic effects on blood pressure, renin-angiotensin system and sodium excretion in normal man. Br J Clin Pharmacol. 1984; 17:233-41. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1463367/ https://pubmed.ncbi.nlm.nih.gov/6324833

46. Johnston CI, Jackson BJ, Larmour I et al. Plasma enalapril levels and hormonal effects after short- and long-term administration in essential hypertension. Br J Clin Pharmacol. 1984; 18:233-9S.

47. Shoback DM, Williams GH, Swartz SL et al. Time course and effect of sodium intake on vascular and hormonal responses to enalapril (MK 421) in normal subjects. J Cardiovasc Pharmacol. 1983; 5:1010-18. https://pubmed.ncbi.nlm.nih.gov/6196548

48. Sanchez RA, Marco E, Gilbert HB et al. Natriuretic effect and changes in renal haemodynamics induced by enalapril in essential hypertension. Drugs. 1985; 30(Suppl 1):49-58. https://pubmed.ncbi.nlm.nih.gov/2994987

49. Biollaz J, Burnier M, Turini GA et al. Three new long-acting converting-enzyme inhibitors: relationship between plasma converting-enzyme activity and response to angiotensin I. Clin Pharmacol Ther. 1981; 29:665-70. https://pubmed.ncbi.nlm.nih.gov/6260419

50. Hodsman GP, Brown JJ, Cumming AMM et al. Enalapril in the treatment of hypertension with renal artery stenosis. BMJ. 1983; 287:1413-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1549614/ https://pubmed.ncbi.nlm.nih.gov/6315126

51. Biollaz J, Brunner HR, Gavras I et al. Antihypertensive therapy with MK 421: angiotensin II-renin relationships to evaluate efficacy of converting enzyme blockade. J Cardiovasc Pharmacol. 1982; 4:966-72. https://pubmed.ncbi.nlm.nih.gov/6185790

52. Brunner DB, Desponds G, Biollaz J et al. Effect of a new angiotensin converting enzyme inhibitor MK 421 and its lysine analogue on the components of the renin system in healthy subjects. Br J Clin Pharmacol. 1981; 11:461-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1401601/ https://pubmed.ncbi.nlm.nih.gov/6268131

53. Griffing GT, Sindler BH, Aurecchia SA et al. Temporal enhancement of renin-aldosterone blockade by enalapril, an angiotensin-converting enzyme inhibitor. Clin Pharmacol Ther. 1982; 32:592-8. https://pubmed.ncbi.nlm.nih.gov/6290130

54. Bauer JH, Gaddy P. Effects of enalapril alone, and in combination with hydrochlorothiazide, on renin-angiotensin-aldosterone, renal function, salt and water excretion, and body fluid composition. Am J Kidney Dis. 1985; 6:222-32. https://pubmed.ncbi.nlm.nih.gov/2996332

55. Shoback DM, Williams GH, Hollenberg NK et al. Endogenous angiotensin II as a determinant of sodium-modulated changes in tissue responsiveness to angiotensin II in normal man. J Clin Endocrin Metab. 1983; 57:764-70.

56. Jackson B, McGrath BP, Johnston CI. Correlation between angiotensin converting enzyme inhibition and the acute hypotensive response to MK 421 in essential hypertension. Clin Exp Pharmacol Physiol. 1982; (Suppl 7):99-104.

57. DiCarlo L, Chatterjee K, Parmley WW et al. Enalapril: a new angiotensin-converting enzyme inhibitor in chronic heart failure: acute and chronic hemodynamic evaluations. J Am Coll Cardiol. 1983; 2:865-71. https://pubmed.ncbi.nlm.nih.gov/6313787

58. MacGregor GA, Markandu ND, Bayliss J et al. Non-sulfhydryl-containing angiotensin-converting enzyme inhibitor (MK421): evidence for role of renin system in normotensive subjects. BMJ. 1981; 283:401-3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1506640/ https://pubmed.ncbi.nlm.nih.gov/6266576

59. Hodsman GP, Brown JJ, Davies DL et al. Converting-enzyme inhibitor enalapril (MK-421) in treatment of hypertension with renal artery stenosis. BMJ. 1982; 285:1697-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1500652/ https://pubmed.ncbi.nlm.nih.gov/6293638

60. Given BD, Taylor T, Hollenberg NK et al. Duration of action and short-term hormonal responses to enalapril (MK 421) in normal subjects. J Cardiovasc Pharmacol. 1984; 6:436-41. https://pubmed.ncbi.nlm.nih.gov/6202969

61. Levine TB, Olivari MT, Garberg V et al. Hemodynamic and clinical response to enalapril, a long-acting converting-enzyme inhibitor, in patients with congestive heart failure. Circulation. 1984; 69:548-53. https://pubmed.ncbi.nlm.nih.gov/6319045

62. Morioka S, Simon G, Cohn JN. Cardiac and hormonal effects of enalapril in hypertension. Clin Pharmacol Ther. 1983; 34:583-9. https://pubmed.ncbi.nlm.nih.gov/6313274

63. Turini GA, Waeber B, Brunner HR. The renin-angiotensin system in refractory heart failure: clinical, hemodynamic and hormonal effects of captopril and enalapril. Eur Heart J. 1983; 4(Suppl A):189-97. https://pubmed.ncbi.nlm.nih.gov/6301835

64. Fitzpatrick D, Nicholls MG, Ikram H et al. Haemodynamic, hormonal, and electrolyte effects of enalapril in heart failure. Br Heart J. 1983; 50:163-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC481390/ https://pubmed.ncbi.nlm.nih.gov/6309203

65. Odya CE, Wilgis FP, Walker JF et al. Immunoreactive bradykinin and [des-Arg⁹]-bradykinin in low-renin essential hypertension—before and after treatment with enalapril (MK 421). J Lab Clin Med. 1983; 102:114-21.

66. Oparil S, Horton R, Wilkins LH et al. Antihypertensive effect of enalapril (MK-421) in low renin essential hypertension: role of vasodilator prostaglandins. Clin Res. 1983; 31:538A.

67. Packer M, Medina N, Yushak M et al. Usefulness of plasma renin activity in predicting haemodynamic and clinical responses and survival during long term converting enzyme inhibition in severe chronic heart failure: experience in 100 consecutive patients. Br Heart J. 1985; 54:298-304. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC481899/ https://pubmed.ncbi.nlm.nih.gov/2994697

68. Weinberger MH, Fineberg NS. Variables predicting blood pressure response to enalapril. Clin Pharmacol Ther. 1984; 35:281.

69. Giudicelli JF, Berdeaux A, Edouard A et al. The effect of enalapril on baroreceptor mediated reflex function in normotensive subjects. Br J Clin Pharmacol. 1985; 20:211-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1400702/ https://pubmed.ncbi.nlm.nih.gov/2994702

70. Ibsen H, Egan B, Osterziel K et al. Reflex-hemodynamic adjustments and baroreflex sensitivity during converting enzyme inhibition with MK-421 in normal humans. Hypertension. 1983; 5:184-91.

71. Ibsen H, Egan B, Julius S. Baroreflex sensitivity during converting enzyme inhibition with enalapril (MK-421) in normal man. J Hypertens. 1983; 1(Suppl 2):222-4.

72. Ajayi AA, Reid JL. The effect of enalapril on baroreceptor mediated reflex function in normotensive subjects. Br J Clin Pharmacol. 1986; 21:338-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1400860/ https://pubmed.ncbi.nlm.nih.gov/3008797

73. Fouad FM, Tarazi RC, Bravo EL et al. Hemodynamic and antihypertensive effects of the new oral angiotensin-converting-enzyme inhibitor MK-421 (enalapril). Hypertension. 1984; 6:167-74. https://pubmed.ncbi.nlm.nih.gov/6327515

74. Millar JA, Derkx FHM, McLean K et al. Absence of reflex tachycardia during converting enzyme inhibition: evidence against impairment of autonomic reflexes. Br J Clin Pharmacol. 1982; 14:129-30P.

75. Dunn FG, Oigman W, Ventura HO et al. Enalapril improves systemic and renal hemodynamics and allows regression of left ventricular mass in essential hypertension. Am J Cardiol. 1984; 53:105-8. https://pubmed.ncbi.nlm.nih.gov/6318542

76. Fitz A, Lawton W, Reimer J et al. The effect of enalapril, a non-thiol converting enzyme inhibitor, on vasoactive factors in hypertension. Clin Res. 1982; 30:775A.

77. Kasai Y, Abe K, Yasujima M et al. Acute effects of MK421, a new angiotensin converting enzyme inhibitor, in man. Tohoku J Exp Med. 1983; 141:417-22. https://pubmed.ncbi.nlm.nih.gov/6322384

78. Freier PA, Wollam GL, Hall WD et al. Blood pressure, plasma volume, and catecholamine levels during enalapril therapy in blacks with hypertension. Clin Pharmacol Ther. 1984; 36:731-7. https://pubmed.ncbi.nlm.nih.gov/6094076

79. Simon G, Morioka S, Snyder DK et al. Increased renal plasma flow in long-term enalapril treatment of hypertension. Clin Pharmacol Ther. 1983; 34:459-65. https://pubmed.ncbi.nlm.nih.gov/6311477

80. Gavras H, Biollaz J, Waeber B et al. Effects of the oral angiotensin-converting enzyme inhibitor MK-421 in human hypertension. Clin Sci. 1981; 61:281-3s. https://pubmed.ncbi.nlm.nih.gov/7021045

81. Bergstrand R, Herlitz H, Johansson S et al. Dose-response relationship of enalapril in mild essential hypertension. Eur Heart J. 1984; 5(Suppl 1):264.

82. Lund-Johansen P, Omvik P. Long-term haemodynamic effects of enalapril (alone and in combination with hydrochlorothiazide) at rest and during exercise in essential hypertension. J Hypertens. 1984; 2(Suppl 2):49-56. https://pubmed.ncbi.nlm.nih.gov/6530537

83. Irvin JD, Till AE, Vlasses PH et al. Bioavailability of enalapril maleate. Clin Pharmacol Ther. 1984; 35:248.

84. Ulm EH, Hichens M, Gomez HJ et al. Enalapril maleate and a lysine analogue (MK-521): disposition in man. Br J Clin Pharmacol. 1982; 14:357-62. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1427630/ https://pubmed.ncbi.nlm.nih.gov/6289858

85. Ulm EH. Enalapril maleate (MK-421), a potent, nonsulfhydryl angiotensin-converting enzyme inhibitor: absorption, disposition, and metabolism in man. Drug Metab Rev. 1983; 14:99-110. https://pubmed.ncbi.nlm.nih.gov/6301792

86. Biollaz J, Schelling JL, Des Combes BJ et al. Enalapril maleate and a lysine analogue (MK-521) in normal volunteers; relationship between plasma drug levels and the renin angiotensin system. Br J Clin Pharmacol. 1982; 14:363-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1427615/ https://pubmed.ncbi.nlm.nih.gov/6289859

87. Till AE, Gomez HJ, Hichens M et al. Pharmacokinetics of repeated single oral doses of enalapril maleate (MK-421) in normal volunteers. Biopharm Drug Dispos. 1984; 5:273-80. https://pubmed.ncbi.nlm.nih.gov/6091806

88. Rocci ML, Shaw EW, Vlasses PH et al. Bioactivation of the angiotensin converting enzyme inhibitor enalapril in cirrhosis. Clin Res. 1986; 34:406A.

89. Saris S, Lowenthal D, Klein L et al. Enalapril maleate in renal failure. Clin Pharmacol Ther. 1984; 34:272.

90. Nakashima M, Nishijima K. Effects in healthy subjects of a new non-thiol-containing angiotensin-converting enzyme inhibitor, enalapril maleate (MK-421). Clin Sci. 1982; 63:183-5s.

91. Swanson BN, Vlasses PH, Ferguson RK et al. Influence of food on the bioavailability of enalapril. J Pharm Sci. 1984; 73:1655-7. https://pubmed.ncbi.nlm.nih.gov/6097665

92. Abrams WB, Davies RO, Gomez HJ. Clinical pharmacology of enalapril. J Hypertens. 1984; 2(Suppl 2):31-6. https://pubmed.ncbi.nlm.nih.gov/6442312

93. Kelly JG, Doyle G, Donohue DJ et al. Pharmacokinetics of enalapril in normal subjects and patients with renal impairment. Br J Clin Pharmacol. 1986; 21:63-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1400811/ https://pubmed.ncbi.nlm.nih.gov/3004546

94. Lowenthal DT, Irvin JD, Merrill D et al. The effect of renal function on enalapril kinetics. Clin Pharmacol Ther. 1985; 38:661-6. https://pubmed.ncbi.nlm.nih.gov/2998676

95. Larmour I, Jackson B, Cubela R et al. Enalapril (MK421) activation in man: importance of liver status. Br J Clin Pharmacol. 1985; 19:701-4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1463833/ https://pubmed.ncbi.nlm.nih.gov/2988590

96. Fruncillo RJ, Rocci ML Jr, Shepley K et al. Enalaprilat accumulates after chronic enalapril dosing in renal failure. Clin Pharmacol Ther. 1985; 37:197.

97. Tocco DJ, deLuna FA, Duncan AEW et al. The physiological disposition and metabolism of enalapril maleate in laboratory animals. Drug Metab Dispos. 1982; 10:15-9. https://pubmed.ncbi.nlm.nih.gov/6124377

98. Gomez HJ, Cirillo VJ, Jones KH. The clinical pharmacology of enalapril. J Hypertens. 1983; 1(Suppl 1):65-70. https://pubmed.ncbi.nlm.nih.gov/6681026

99. Howlett DR. In vitro hydrolysis of the angiotensin converting enzyme inhibitor enalapril (MK-421) by plasma and liver. Br J Pharmacol. 1983; 79(Suppl):324.

100. Schwartz JB, Taylor A, Abernethy D et al. Pharmacokinetics and pharmacodynamics of enalapril in patients with congestive heart failure and patients with hypertension. J Cardiovasc Pharmacol. 1985; 7:767-76. https://pubmed.ncbi.nlm.nih.gov/2410720

101. Shionoiri H, Gotoh E, Akiba N et al. Blood concentration and effect of enalapril on blood pressure, renin angiotensin system and kallikrein kinin system in patients with essential hypertension. Circulation. 1983; 68:348. https://pubmed.ncbi.nlm.nih.gov/6683132

102. Hockings N, Ajayi AA, Reid JL. Age and the pharmacokinetics of angiotensin converting enzyme inhibitors enalapril and enalaprilat. Br J Clin Pharmacol. 1986; 21:341-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1400946/ https://pubmed.ncbi.nlm.nih.gov/3011046

103. Ajayi AA, Hockings N, Reid JL. Age and the pharmacodynamics of angiotensin converting enzyme inhibitors enalapril and enalaprilat. Br J Clin Pharmacol. 1986; 21:349-57. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1400941/ https://pubmed.ncbi.nlm.nih.gov/3011047

104. Millar JA, Derkx FHM, McLean K et al. Pharmacodynamics of converting enzyme inhibition: the cardiovascular, endocrine and autonomic effects of MK421 (enalapril) and MK521. Br J Clin Pharmacol. 1982; 14:347-55. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1427629/ https://pubmed.ncbi.nlm.nih.gov/6289857

105. The Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The 1984 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1984; 144:1045-57. https://pubmed.ncbi.nlm.nih.gov/6143542

106. Anon. Drugs for hypertension. Med Lett Drugs Ther. 1984; 26:107-12. https://pubmed.ncbi.nlm.nih.gov/6150424

107. Nadeau JH, Oates JA, Wood AJJ. Characterization of the hypotensive and sympathetic response to enalapril. Clin Pharmacol Ther. 1984; 35:261.

108. Gavras H, Waeber B, Gavras I et al. Antihypertensive effect of the new oral angiotensin converting enzyme inhibitor MK-421. Lancet. 1981; 2:543-7. https://pubmed.ncbi.nlm.nih.gov/6116000

109. Sassano P, Chatellier G, Alhenc-Gelas F et al. Antihypertensive effect of enalapril as first-step treatment of mild and moderate uncomplicated essential hypertension: evaluation by two methods of blood pressure measurement. Am J Med. 1984; 77(Suppl 2A):18-22. https://pubmed.ncbi.nlm.nih.gov/6089555

110. Brunner HR, Waeber B, Nussberger J et al. Long-term clinical experience with enalapril in essential hypertension. J Hypertens. 1983; 1(Suppl 1):103-7. https://pubmed.ncbi.nlm.nih.gov/6681024

111. Bauer JH. Role of angiotensin converting enzyme inhibitors in essential and renal hypertension. Am J Med. 1984; 77(Suppl 2A):43-51. https://pubmed.ncbi.nlm.nih.gov/6206722

112. Jones RI, Hornung RS, Cashman PMM et al. Effect of enalapril at rest, during tilt, static and dynamic exercise in systemic hypertension. Am J Cardiol. 1985; 55:1534-8. https://pubmed.ncbi.nlm.nih.gov/2988326

113. Izzo JL Jr, Larrabee PS, Kamm DE. Physiologic adaptation to chronic angiotensin converting enzyme inhibition (ACEI). Clin Pharmacol Ther. 1984; 35:248.

114. Cooper WD, Doyle G, Donohoe J et al. Enalapril in the treatment of hypertension associated with impaired renal function. Br J Clin Pharmacol. 1985; 20:280-1P.

115. Smith CD, Smith RD, Korn JH. Hypertensive crisis in systemic sclerosis: treatment with the new oral angiotensin converting enzyme inhibitor MK 421 (enalapril) in captopril-intolerant patients. Arthritis Rheum. 1984; 27:826-8. https://pubmed.ncbi.nlm.nih.gov/6331462

116. Hodsman GP, Brown JJ, Cumming AMM et al. Enalapril in treatment of hypertension with renal artery stenosis: changes in blood pressure, renin, angiotensin I and II, renal function, and body composition. Am J Med. 1984; 77:52-60.

117. Webster J, Newnham DM, Petrie JC. Initial dose of enalapril in hypertension. BMJ. 1985; 290:1623-4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1415786/ https://pubmed.ncbi.nlm.nih.gov/2988687

118. Jones RI, Hornung RS, Cashman PMM et al. Duration and diurnal variation of the hypotensive effect of enalapril in patients with essential hypertension. J Am Coll Cardiol. 1984; 3:616.

119. O’Keefe CL, Prior N, Yaffe J et al. Individualized antihypertensive therapy with enalapril/hydrochlorothiazide: use of 24 hour ambulatory blood pressure monitoring. Circulation. 1983; 68:III-37.

120. Nelson EB, Pool JL, Taylor AA et al. Long term efficacy of enalapril plus hydrochlorothiazide in the treatment of essential hypertension. Clin Pharmacol Ther. 1983; 33:230.

121. Chrysant SG, Brown RD, Kem DC et al. Antihypertensive and metabolic effects of a new converting enzyme inhibitor, enalapril. Clin Pharmacol Ther. 1983; 33:741-6. https://pubmed.ncbi.nlm.nih.gov/6303673

122. Vlasses PH, Rotmensch HH, Swanson BN et al. Comparative antihypertensive effects of enalapril maleate and hydrochlorothiazide, alone and in combination. J Clin Pharmacol. 1983; 23:227-33. https://pubmed.ncbi.nlm.nih.gov/6308068

123. Bauer JH, Jones LB. Comparative studies: enalapril versus hydrochlorothiazide as first-step therapy for the treatment of primary hypertension. Am J Kidney Dis. 1984; 4:55-64. https://pubmed.ncbi.nlm.nih.gov/6331157

124. Bauer JH, Reams GP. Hemodynamic and renal function in essential hypertension during treatment with enalapril. Am J Med. 1985; 79(Suppl 3C):10-3. https://pubmed.ncbi.nlm.nih.gov/2996341

125. Ream GP, Bauer JH. Effect of enalapril in subjects with hypertension associated with moderate to severe renal dysfunction. Arch Intern Med. 1986; 146:2145-8. https://pubmed.ncbi.nlm.nih.gov/3022660

126. Bauer JH, Reams GP. Antihypertensive treatment in patients with renal disease: control of glomerular hypertension. Kidney. (in press)

127. Griffing GT, Melby JC. Concomitant blockade and activation of the renin-aldosterone system by an angiotensin-converting enzyme inhibitor (MK-421) and hydrochlorothiazide. Curr Ther Res. 1982; 32:396-405.

128. Andrèn L, Weiner L, Svensson A et al. Enalapril with either a “very low” or “low” dose of hydrochlorothiazide is equally effective in essential hypertension: a double-blind trial in 100 hypertensive patients. J Hypertens. 1983; 1(Suppl 2):384-6.

129. Sassano P, Chatellier G, Amiot AM et al. A double-blind randomized evaluation of converting enzyme inhibition as the first-step treatment of mild to moderate hypertension. J Hypertens. 1984; 2(Suppl 2):75-80.

130. van Schaik BAM, Geyskes GG, Roos JC et al. Changes in blood pressure and body fluid during diuretic therapy in patients with essential hypertension who receive enalapril. Clin Pharmacol Ther. 1986; 39:60-4. https://pubmed.ncbi.nlm.nih.gov/3002701

131. Malini PL, Strocchi E, Ambrosioni E et al. Long-term antihypertensive, metabolic and cellular effects of enalapril. J Hypertens. 1984; 2(Suppl 2):101-5.

132. Golub M, Eggena P, Barrett J et al. Renin-angiotensin, hemodynamic and renal responses to enalapril with and without hydrochlorothiazide in essential hypertension. Clin Res. 1984; 32:242A.

133. Taguma Y, Kitamoto Y, Futaki G et al. Effect of captopril on heavy proteinuria in azotemic diabetics. N Engl J Med. 1985; 313:1617-20. https://pubmed.ncbi.nlm.nih.gov/3906398

134. Gabriel MA, Tsianco MC, Kramsch DM et al. Once-a-day enalapril compared with atenolol in hypertension. Clin Pharmacol Ther. 1985; 37:198.

135. Arr SM, Burgess J, Cooper WD et al. A comparative study of enalapril and atenolol in moderate to severe hypertension. Br J Clin Pharmacol. 1984; 18:292-3P.

136. Helgeland A, Strommen R, Hagelund CH et al. Enalapril, atenolol, and hydrochlorothiazide in mild to moderate hypertension. Lancet. 1986; 1:872. https://pubmed.ncbi.nlm.nih.gov/2870352

137. van Schaik BAM, Geyskes GG, Kettner N et al. Comparison of enalapril and propranolol in essential hypertension. Eur J Clin Pharmacol. 1986; 29:511-6. https://pubmed.ncbi.nlm.nih.gov/3007162

138. Gotzsche PC, Safar M, Helgeland A. Enalapril, atenolol, and hydrochlorothiazide in hypertension. Lancet. 1986; 38-9. Letter.

139. O’Connor DT, Mosley CA, Cervenka J et al. Contrasting renal haemodynamic responses to the angiotensin converting enzyme inhibitor enalapril and the beta-adrenergic antagonist metoprolol in essential hypertension. J Hypertens. 1984; 2(Suppl 2):89-92.

140. Winer N, Carter CH. Effect on enalapril (MK-421) and metoprolol (MIP) of blood pressure, converting enzyme, renin, and catecholamines. Clin Pharmacol Ther. 1983; 33:232.

141. Burnier M, Biollaz J, Brunner HR et al. Comparison in normal volunteers of three converting enzyme inhibitors: RHC 3659, MK 421 and captopril. Am J Cardiol. 1982; 49:1550-1. https://pubmed.ncbi.nlm.nih.gov/6280484

142. Vlasses PH, Conner DP, Rotmensch HH et al. Double-blind comparison of captopril and enalapril in mild to moderate hypertension. J Am Coll Cardiol. 1986; 7:651-60. https://pubmed.ncbi.nlm.nih.gov/3005384

143. Kochar MS, Woods K, Kalbfleisch JH et al. Enalapril vs captopril as step II and methyldopa as step III drugs in hypertension. Curr Ther Res. 1985; 38:694-701.

144. Thind GS, Johnson A, Bhatnagar D et al. A parallel study of enalapril and captopril and 1 year of experience with enalapril treatment in moderate-to-severe essential hypertension. Am Heart J. 1985; 109:852-8. https://pubmed.ncbi.nlm.nih.gov/2984913

145. Lindsjö M, Danielson BG, Weiss L et al. Enalapril treatment in a patient with impaired renal function and intolerance to captopril. Scand J Urol Nephrol. 1984; 79:99-102.

146. McGrath BP, Arnolda L, Matthews PG et al. Controlled trial of enalapril in congestive cardiac failure. Br Heart J. 1985; 54:405-14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC481919/ https://pubmed.ncbi.nlm.nih.gov/2996575

147. Kromer EP, Riegger GAJ, Liebau G et al. Effectiveness of converting enzyme inhibition (enalapril) for mild congestive heart failure. Am J Cardiol. 1986; 57:459-62. https://pubmed.ncbi.nlm.nih.gov/3004187

148. Cody RJ, Covit AB, Schaer GL et al. Evaluation of a long-acting converting enzyme inhibitor (enalapril) for the treatment of chronic congestive heart failure. J Am Coll Cardiol. 1983; 14:1154-9.

149. Kubo SH, Cody RJ, Laragh JH et al. Immediate converting-enzyme inhibition with intravenous enalapril in chronic congestive heart failure. Am J Cardiol. 1985; 55:122-6. https://pubmed.ncbi.nlm.nih.gov/2981462

150. Dunkman WB, Wilen M, Franciosa JA. Enalapril (MK-421), a new angiotensin-converting enzyme inhibitor: acute and chronic effects in heart failure. Chest. 1983; 84:539-45. https://pubmed.ncbi.nlm.nih.gov/6313304

151. Webster MWI, Fitzpatrick MA, Nicholls MG et al. Effect of enalapril on ventricular arrhythmias in congestive heart failure. Am J Cardiol. 1985; 56:566-9. https://pubmed.ncbi.nlm.nih.gov/2994451

152. Packer M, Lee WH, Yushak M et al. Comparison of captopril and enalapril in patients with severe chronic heart failure. N Engl J Med. 1986; 315:847-53. https://pubmed.ncbi.nlm.nih.gov/3018566

153. Dickstein K, Gundersen T. Successful management of severe congestive cardiac failure with enalapril. Am J Med. 1983; 75:721-3. https://pubmed.ncbi.nlm.nih.gov/6312795

154. Moncloa F, Sromovsky JA, Walker JF et al. Enalapril in hypertension and congestive heart failure: overall review of efficacy and safety. Drugs. 1985; 30(Suppl 1):82-9. https://pubmed.ncbi.nlm.nih.gov/2864229

155. Gavras I, Gavras H. Captopril and enalapril. Ann Intern Med. 1983; 98:556-7. https://pubmed.ncbi.nlm.nih.gov/6301322

156. Simon AC, Levenson JA, Bouthier JD et al. Comparison of oral MK 421 and propranolol in mild to moderate essential hypertension and their effects on arterial and venous vessels of the forearm. Am J Cardiol. 1984; 53:781-5. https://pubmed.ncbi.nlm.nih.gov/6322565

157. Guthrie GP Jr, Hammond J, Kotchen TA. Abrupt cessation of enalapril (MK-421) in essential hypertension. Clin Res. 1982; 30:733A.

158. Sharpe DN, Murphy J, Coxon R et al. Enalapril in patients with chronic heart failure: a placebo-controlled, randomized, double-blind study. Circulation. 1984; 70:271-8. https://pubmed.ncbi.nlm.nih.gov/6329547

159. Cleland JGF, Dargie HJ, Gillen G et al. Effects of enalapril on clinical state and serum electrolytes in congestive heart failure. Br J Clin Pharmacol. 1985; 19:542-3P.

160. Marre M, Leblanc H, Passa P. Effects of converting enzyme inhibition with enalapril administered to hypertensive insulin-dependent diabetics (IDD). J Hypertens. 1985; 3:552.

161. Murphy BF, Whitworth JA, Kincaid-Smith P. Renal insufficiency with combinations of angiotensin converting enzyme inhibitors and diuretics. BMJ. 1984; 299:844-5.

162. Griffing GT, Melby JC. The therapeutic use of a new potassium-sparing diuretic, amiloride, and a converting enzyme inhibitor, MK-421, in preventing hypokalemia associated with primary and secondary hyperaldosteronism. Clin Exp Hypertens Theory Pract. 1983; 5:779-801.

163. Ferguson RK, Vlasses PH, Irvin JD et al. A comparative pilot study of enalapril, a new converting enzyme inhibitor, and hydrochlorothiazide in essential hypertension. J Clin Pharmacol. 1982; 22:281-9. https://pubmed.ncbi.nlm.nih.gov/6286734

164. Coulshed DJ, Davies SJ, Turney JH. Prolonged hypotension after fever during enalapril treatment. Lancet. 1985; 2:222. https://pubmed.ncbi.nlm.nih.gov/2862409

165. Cleland JGF, Dargie HJ, McAlpine H et al. Severe hypotension after first dose of enalapril in heart failure. BMJ. 1985; 291:1309-12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1417403/ https://pubmed.ncbi.nlm.nih.gov/2998536

166. Cressman MD, Vidt DG, Acker C. Renal glycosuria and azotaemia after enalapril maleate (MK-421). Lancet. 1982; 2:440. https://pubmed.ncbi.nlm.nih.gov/6124829

167. Bender W, La France N, Walker WG. Mechanism of deterioration in renal function in patients with renovascular hypertension treated with enalapril. Hypertension. 1984; 6(Suppl 1):I193-7. https://pubmed.ncbi.nlm.nih.gov/6327522

168. McFate Smith W, Davies RO, Gabriel MA et al. Tolerance and safety of enalapril. Br J Clin Pharmacol. 1984; 18:249-53S.

169. Franklin SS, Smith RD. Comparison of effects of enalapril plus hydrochlorothiazide versus standard triple therapy on renal function in renovascular hypertension. Am J Med. 1985; 79(Suppl 3C):14-23. https://pubmed.ncbi.nlm.nih.gov/2996342

170. Brivet F, Roulot D, Poitrine A et al. Reversible acute renal failure during enalapril treatment in patient with chronic glomerulonephritis without renal artery stenosis. Lancet. 1985; 1:1512. https://pubmed.ncbi.nlm.nih.gov/2861442

171. Studer A, Vetter W. Reversible leucopenia associated with angiotensin-converting-enzyme inhibitor MK-421. Lancet. 1982; 1:458. https://pubmed.ncbi.nlm.nih.gov/6121132

172. Barnes JN, Davies ES, Gent CB. Rash, eosinophilia, and hyperkalaemia associated with enalapril. Lancet. 1983; 2:41-2. https://pubmed.ncbi.nlm.nih.gov/6134901

173. Semple PF, Herd GW. Cough and wheeze caused by inhibitors of angiotensin-converting enzyme. N Engl J Med. 1986; 314:61. https://pubmed.ncbi.nlm.nih.gov/2999601

174. Izzo JL, Larrabee PS, Scandling JD. Hyperkalemia with enalapril in advanced renal failure. JAMA. 1986; 255:2605-6. https://pubmed.ncbi.nlm.nih.gov/3009908

175. DiBianco R. Adverse reactions with angiotensin converting enzyme (ACE) inhibitors. Med Toxicol. 1986; 1:122-41. https://pubmed.ncbi.nlm.nih.gov/3023783

176. McMurray J, Fraser DM. Captopril, enalapril, and blood glucose. Lancet. 1986; 1:1035. https://pubmed.ncbi.nlm.nih.gov/2871313

177. Passa P, Marre M, Leblanc H. Enalapril, captopril, and blood glucose. Lancet. 1986; 1:1447. https://pubmed.ncbi.nlm.nih.gov/2872551

178. Waeber B, Nussberger J, Brunner HR. Self poisoning with enalapril. BMJ. 1984; 288:287-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1444051/ https://pubmed.ncbi.nlm.nih.gov/6318878

179. Lau CP. Attempted suicide with enalapril. N Engl J Med. 1986; 315:197. https://pubmed.ncbi.nlm.nih.gov/3014333

180. Douste-Blazy P, Rostin M, Livarek B et al. Angiotensin converting enzyme inhibitors and lithium treatment. Lancet. 1986; 1:1448. https://pubmed.ncbi.nlm.nih.gov/2872554

181. Bergstrand R, Johansson S, Vedin A et al. Comparison of once-a-day and twice-a-day dosage regimens of enalapril (MK-421) in patients with mild hypertension. Br J Clin Pharmacol. 1982; 14:136-7P.

182. Bergstrand R, Herlitz H, Johansson S et al. Effective dose range of enalapril in mild to moderate essential hypertension. Br J Clin Pharmacol. 1985; 19:605-11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1463850/ https://pubmed.ncbi.nlm.nih.gov/2988589

183. Cleland J, McAlpine H, Semple P et al. First dose hypotension with angiotensin converting enzyme inhibitors in heart failure. Br Heart J. 1985; 53:672-3.

184. Jackson B, Murphy BF, Johnston CI et al. Renovascular hypertension: treatment with the oral angiotensin-converting enzyme inhibitor enalapril. Am J Nephrol. 1986; 6:182-6. https://pubmed.ncbi.nlm.nih.gov/3017107

185. Kubo SH, Cody RJ. Enalapril, a rash, and captopril. Ann Intern Med. 1984; 100:616. https://pubmed.ncbi.nlm.nih.gov/6322634

186. Fernandez PG, Kim BK, Galway AB. An appraisal of antihypertensive efficacy and adverse reactions with two drug regimens: enalapril maleate as part of triple therapy compared to conventional triple therapy in moderate to severe hypertension. Pharmatherapeutica. 1984; 3:505-14. https://pubmed.ncbi.nlm.nih.gov/6322207

187. Kubo SH, Cody RJ. Clinical pharmacokinetics of the angiotensin converting enzyme inhibitors: a review. Clin Pharmacokinet. 1985; 10:377-91. https://pubmed.ncbi.nlm.nih.gov/2994938

188. Lee CSC, Marbury TC. Drug therapy in patients undergoing haemodialysis: clinical pharmacokinetic considerations. Clin Pharmacokinet. 1984; 9:42-66. https://pubmed.ncbi.nlm.nih.gov/6362952

189. Pond SM. Renal principles: diuresis, dialysis, and hemoperfusion. In: Goldfrank LR, Flomenbaum NE, Lewin NA et al, eds. Goldfrank’s toxicologic emergencies. 3rd ed. Norwalk, CT: Appleton-Century-Crofts; 1986:102-15.

190. Pang KS, Cherry WF, Ulm EH. Disposition of enalapril in the perfused rat intestine-liver preparation: absorption, metabolism and first-pass effect. J Pharmacol Exp Ther. 1985; 233:788-95. https://pubmed.ncbi.nlm.nih.gov/2989498

191. Lant AF, McNabb RW, Noormohamed FH. Kinetic and metabolic aspects of enalapril action. J Hypertens. 1984; 2(Suppl 2):37-42. https://pubmed.ncbi.nlm.nih.gov/6530536

192. McNabb WR, Noormohamed FH, Brooks BA et al. Effects of repeated doses of enalapril on renal function in man. Br J Clin Pharmacol. 1985; 19:353-61. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1463726/ https://pubmed.ncbi.nlm.nih.gov/2985103

193. Pang KS, Cherry WF, Terrell JA et al. Disposition of enalapril and its diacid metabolite, enalaprilat, in a perfused rat liver preparation: presence of a diffusional barrier for enalaprilat into hepatocytes. Drug Metab Dispos. 1984; 12:309-13. https://pubmed.ncbi.nlm.nih.gov/6145558

194. Gibson TP, Matusik E, Nelson LD et al. Artificial kidneys and clearance calculations. Clin Pharmacol Ther. 1976; 20:720-6. https://pubmed.ncbi.nlm.nih.gov/991541

195. Pond S, Rosenberg J, Benowitz NL et al. Pharmacokinetics of haemoperfusion for drug overdose. Clin Pharmacokinet. 1979; 4:329-54. https://pubmed.ncbi.nlm.nih.gov/389527

196. Cohen ML, Kurz KD. Angiotensin converting enzyme inhibition in tissues from spontaneously hypertensive rats after treatment with captopril or MK-421. J Pharmacol Exp Ther. 1982; 220:63-9. https://pubmed.ncbi.nlm.nih.gov/6273529

197. Yasujima M, Abe K, Kasai Y et al. Renal kallikrein-kinin system and the depressor effect of angiotensin converting enzyme inhibitors MK 421, SA 446, and captopril in rats. Clin Exp Hypertens. 1984; 6:1207-25.

198. Zusman RM. Alternatives to traditional antihypertensive therapy. Hypertension. 1986; 8:837-9. https://pubmed.ncbi.nlm.nih.gov/2875945

199. Moser M. Initial treatment of adult patients with essential hypertension. Part 1: why conventional stepped-care therapy of hypertension is still indicated. Pharmacotherapy. 1985; 5:189-95. https://pubmed.ncbi.nlm.nih.gov/2863806

200. Kaplan NM. Initial treatment of adult patients with essential hypertension. Part 2: alternating monotherapy is the preferred treatment. Pharmacotherapy. 1985; 5:195-200. https://pubmed.ncbi.nlm.nih.gov/4034407

201. Bauer JH. Stepped-care approach to the treatment of hypertension: is it obsolete? (unpublished observations)

202. Imai Y, Abe K, Seino M et al. Attenuation of pressor responses to norepinephrine and pitressin and potentiation of pressor response to angiotensin II by captopril in human subjects. Hypertension. 1982; 4:444-51. https://pubmed.ncbi.nlm.nih.gov/7040234

203. Reams GP, Bauer JH, Gaddy P. Use of the converting enzyme inhibitor enalapril in renovascular hypertension: effect on blood pressure, renal function, and the renin-angiotensin-aldosterone system. Hypertension. 1986; 8:290-7. https://pubmed.ncbi.nlm.nih.gov/3007351

204. Reams GP, Bauer JH. Enalapril versus triple-drug therapy in the treatment of renovascular hypertension. Drugs. 1985; 30(Suppl 1):59-69. https://pubmed.ncbi.nlm.nih.gov/2994988

205. Chobanian AV. Antihypertensive therapy in evolution. N Engl J Med. 1986; 314:1701-2. https://pubmed.ncbi.nlm.nih.gov/3713773

206. World Health Organization/International Society of Hypertension Fourth Mild Hypertension Conference. 1986 guidelines for the treatment of mild hypertension: memorandum from the WHO/ISH. Hypertension. 1986; 8:957-61.

207. Subcommittee on Nonpharmacological Therapy of the 1984 Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Nonpharmacological approaches to the control of high blood pressure: final report. Hypertension. 1986; 8:444-67. https://pubmed.ncbi.nlm.nih.gov/3009327

208. Anon. Captopril: benefits and risks in severe hypertension. Lancet. 1980; 2:129-30. https://pubmed.ncbi.nlm.nih.gov/6105297

209. Vlasses PH, Ferguson RK, Chatterjee K. Captopril: clinical pharmacology and benefit-to-risk ratio in hypertension and congestive heart failure. Pharmacotherapy. 1982; 2:1-17. https://pubmed.ncbi.nlm.nih.gov/6765388

210. Waeber B, Gavras I, Brunner HR et al. Safety and efficacy of chronic therapy with captopril in hypertensive patients: an update. J Clin Pharmacol. 1981; 21:508-16. https://pubmed.ncbi.nlm.nih.gov/6460791

211. Rotmensch HH, Vlasses PH, Ferguson RK. Resolution of captopril-induced rash after substitution of enalapril. Pharmacotherapy. 1983; 3:131-3. https://pubmed.ncbi.nlm.nih.gov/6304662

212. Lopez-Ovejero JA, Saal SD, D’Angelo WA et al. Reversal of vascular and renal crises of scleroderma by oral angiotensin-converting-enzyme blockade. N Engl J Med. 1979; 300:1417-9. https://pubmed.ncbi.nlm.nih.gov/220537

213. D’Angelo WA, Lopez-Ovejero JA, Saal SD et al. Early versus late treatment of scleroderma renal crisis and malignant hypertension with captopril. Arthritis Rheum. 1980; 23:664.

214. Whitman HH, Case DB, Botstein G et al. Variable response to oral converting enzyme blockade in hypertensive scleroderma patients. Arthritis Rheum. 1980; 23:762-3.

215. Heel RC, Brogden RN, Speight TM et al. Captopril: a preliminary review of its pharmacological properties and therapeutic efficacy. Drugs. 1980; 20:409-52. https://pubmed.ncbi.nlm.nih.gov/7009133

216. Velletri P, Bean BL. The effects of captopril on rat aortic angiotensin-converting enzyme. J Cardiovasc Pharmacol. 1982; 4:315-25. https://pubmed.ncbi.nlm.nih.gov/6175817

217. Vlasses PH, Ferguson RK, Smith JB et al. Urinary excretion of prostacyclin and thromboxane A₂ metabolites after angiotensin converting enzyme inhibition in hypertensive patients. Prostaglandins Leukotrienes Med. 1983; 11:143-50.

218. Yasujima M, Matthews G, Johnston CI. Decreased uterine bradykinin receptors during captopril infusion in rats. Am J Cardiol. 1982; 49:1518-20. https://pubmed.ncbi.nlm.nih.gov/6122372

219. Reams GP, Bauer JH. Humoral effect of long-term oral enalapril therapy. Am J Kidney Dis. 1986; 5:402-6.

220. Reams GP, Bauer JH. Long-term effects of enalapril monotherapy and enalapril/hydrochlorothiazide combination therapy on blood pressure, renal function, and body fluid composition. J Clin Hypertens. 1986; 1:55-63.

221. De Jonge A, Wilffert B, Kalkman HO et al. Captopril impairs the vascular smooth muscle contraction mediated by postsynaptic α₂- adrenoceptors in the pithed rat. Eur J Pharmacol. 1981; 74:385-6. https://pubmed.ncbi.nlm.nih.gov/6271562

222. Edwards CRW, Padfield PL. Angiotensin-converting enzyme inhibitors: past, present, and bright future. Lancet. 1985; 1:30-4. https://pubmed.ncbi.nlm.nih.gov/2856956

223. Frohlich ED, Cooper RA, Lewis EJ. Review of the overall experience of captopril in hypertension. Arch Intern Med. 1984; 144:1441-4. https://pubmed.ncbi.nlm.nih.gov/6233948

224. Dzau VJ. Significance of the vascular renin-angiotensin pathway. Hypertension. 1986; 8:553-9. https://pubmed.ncbi.nlm.nih.gov/3013773

225. Packer M, Lee WH, Kessler PD. Preservation of glomerular filtration rate in human heart failure by activation of the renin-angiotensin system. Circulation. 1986; 74:766-74. https://pubmed.ncbi.nlm.nih.gov/3019586

226. Bristol-Myers Squibb Company. Capoten (captopril) tablets prescribing information (J4-458K). Princeton, NJ; 1998 Dec.

227. Ferguson RK, Vlasses PH. Clinical pharmacology and therapeutic applications of the new oral angiotensin converting enzyme inhibitor, captopril. Am Heart J. 1981; 101:650-6. https://pubmed.ncbi.nlm.nih.gov/6261570

228. Okamura T, Miyazaki M, Inagami T et al. Vascular renin-angiotensin system in two-kidney, one clip hypertensive rats. Hypertension. 1986; 8:560-5. https://pubmed.ncbi.nlm.nih.gov/3013774

229. Ferriere M, Lachkar H, Richard JL et al. Captopril and insulin sensitivity. Ann Intern Med. 1985; 102:134-5. https://pubmed.ncbi.nlm.nih.gov/3881067

230. Griffing GT, Sindler BH, Aurecchia SA et al. Reversal of diuretic-induced secondary hyperaldosteronism and hypokalemia by enalapril (MK-421): a new angiotensin-converting enzyme inhibitor. Metabolism. 1983; 32:711-6. https://pubmed.ncbi.nlm.nih.gov/6306388

231. Reviewers’ comments (personal observations); 1986 Nov.

232. Griffing GT, Melby JC. Enalapril (MK-421) and the white cell count and haematocrit. Lancet. 1982; 1:1361. https://pubmed.ncbi.nlm.nih.gov/6123665

233. Blythe WB. Captopril and renal autoregulation. N Engl J Med. 1983; 308:390-1. https://pubmed.ncbi.nlm.nih.gov/6337329

234. Hricik DE, Browning PJ, Kopelman R et al. Captopril-induced renal insufficiency in patients with bilateral renal-artery stenoses or renal-artery stenosis in a solitary kidney. N Engl J Med. 1983; 308:373-6. https://pubmed.ncbi.nlm.nih.gov/6337327

235. Hansten PD, Horn JR. Captopril (Capoten) interactions. Drug Interact Newsl. 1985; 5(Updates):U10-1.

236. Hansten PD, Horn JR. Angiotensin converting enzyme (ACE) inhibitors captopril (Capoten), enalapril (Vasotec). Drug Interact Newsl. 1986; 6(Updates):U17-8.

237. Funck-Brentano C, Chatellier G, Alexandre JM. Reversible renal failure after combined treatment with enalapril and furosemide in a patient with congestive heart failure. Br Heart J. 1986; 55:596-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1236768/ https://pubmed.ncbi.nlm.nih.gov/3013264

238. Griffing GT, Sindler BH, Aurecchia SA et al. The therapeutic effect of a new angiotensin-converting enzyme inhibitor, enalapril maleate, in idiopathic hyperaldosteronism. Clin Res. 1982; 30:692A.

239. Packer M, Kessler PD, Gottlieb SS. Adverse effects of converting-enzyme inhibition in patients with severe congestive heart failure: pathophysiology and management. Postgrad Med J. 1986; 62(Suppl 1):179-82. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2418629/ https://pubmed.ncbi.nlm.nih.gov/3022272

240. Packer M, Medina N, Yushak M. Relation between serum sodium concentration and the hemodynamic and clinical responses to converting enzyme inhibition with captopril in severe heart failure. J Am Coll Cardiol. 1984; 3:1035-43. https://pubmed.ncbi.nlm.nih.gov/6323565

241. Sesoko S, Kaneko Y. Cough associated with the use of captopril. Arch Intern Med. 1985; 145:1524. https://pubmed.ncbi.nlm.nih.gov/3896184

242. Irvin JD, Viau JM. Safety profiles of the angiotensin converting enzyme inhibitors captopril and enalapril. Am J Med. 1986; 81(Suppl 4C):46-50. https://pubmed.ncbi.nlm.nih.gov/3022584

243. Bauer JH, Reams GP. Renal effects of angiotensin converting enzyme inhibitors in hypertension. Am J Med. 1986; 81(Suppl 4C):19-27. https://pubmed.ncbi.nlm.nih.gov/3022581

244. Dal Pino AE. (Merck Sharp & Dohme, West Point, PA): Personal communication; 1986 Dec.

245. Merck Sharp & Dohme. Vasotec (enalapril maleate) prescribing information. West Point, PA; 1989 Aug.

246. Golub M, Eggena P, Barrett J et al. Cyclooxygenase inhibitors do not influence the blood pressure response to the converting enzyme inhibitor enalapril. Paper presented at 10th scientific meeting of the International Society of Hypertension. Interlaken, Switzerland: 1984 June 17-21. Abstract No. 398.

247. Herrera-Acosta J, Péerez-Grovas H, Fernéandez M et al. Enalapril in essential hypertension. Drugs. 1985; 30(Suppl 1):35-46. https://pubmed.ncbi.nlm.nih.gov/2994986

248. Levenson JA, Safar ME, Simon AC et al. Effect of oral MK-421 and propranolol on the forearm arterial circulation in essential hypertension: a preliinary report. J Hypertension. 1983; 1(Suppl 1):101-2.

249. Lessem JN, Rucinska E, Vickers et al. Long-term enalapril—a new converting enzyme inhibitor—in the treatment of mild to moderate essential hypertension, results of a worldwide multiclinic study. Comparing two ways of analyzing data. Clin Exper Hypertension Theory Pract. 1985; A7:1515-39.

250. Semplicini A, Rossi GP, Bongiovi S et al. Time course of changes in blood pressure, aldosterone and body fluids during enalapril treatment: a double-blind randomized study vs hydrochlorothiazide plus propranolol in essential hypertension. Clin Exp Pharmacol Physiol. 1986; 13:17-24. https://pubmed.ncbi.nlm.nih.gov/3011329

251. Jaffe IA. Adverse effects profile of sulfhydryl compounds in man. Am J Med. 1986; 80:471-6. https://pubmed.ncbi.nlm.nih.gov/2937293

252. Webb D, Benjamin N, Collier J et al. Enalapril-induced cough. Lancet. 1986; 2:1094. https://pubmed.ncbi.nlm.nih.gov/2877240

253. Israel-Biet D, Delaisements C, Chretien J. Enalapril-induced cough. Lancet. 1986; 2:918. https://pubmed.ncbi.nlm.nih.gov/2876346

254. Merck & Co. Vaseretic (enalapril maleate–hydrochlorothiazide) prescribing information. Whitehouse Station, NJ; 2001 Jan.

255. Inman WHW, Rawson NSB. Deafness with enalapril and prescription event monitoring. Lancet. 1987; 1:872.

256. Ollivier JP, Ducrocq MB, Droniou J. Un effet secondaire des inhibiteurs de l’enzyme de conversion: la toux. Presse Med. 1987; 16:759-61. https://pubmed.ncbi.nlm.nih.gov/3035534

257. Nicholls MG, Gilchrist N. Sulindac and cough induced by converting enzyme inhibitors. Lancet. 1987; 1:872. https://pubmed.ncbi.nlm.nih.gov/2882285

258. Inman WHW. Enalapril-induced cough. Lancet. 1986; 2:1218.

259. Fennerty A, Littley M, Reid P. Enalapril-induced nasal blockage. Lancet. 1986; 2:1395-6. https://pubmed.ncbi.nlm.nih.gov/2878252

260. The Consensus Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure: results of the cooperative North Scandinavian enalapril survival study (consensus). N Engl J Med. 1987; 316:1429-34. https://pubmed.ncbi.nlm.nih.gov/2883575

261. Mangini RJ, ed. Drug interaction facts. St. Louis: JB Lippincott Co; 1987(Oct):204a.

262. Packler M, Lee WH, Medina M et al. Functional renal insufficiency during long-term therapy with captopril and enalapril in severe chronic heart failure. Ann Intern Med. 1987; 106:346-54. https://pubmed.ncbi.nlm.nih.gov/3028221

263. Schubiger G, Flury G, Nussberger J. Enalapril for pregnancy-induced hypertension: acute renal failure in a neonate. Ann Intern Med. 1988; 108:215-6. https://pubmed.ncbi.nlm.nih.gov/2829674

264. Bennett WM, Aronoff GR, Golper TA et al. Drug prescribing in renal failure: dosing guidelines for adults. Philadelphia: American College of Physicians; 1987:36-7.

265. Powers ER, Chiaramida A, De Maria AN et al. A double-blind comparison of lisinopril with captopril in patients with symptomatic congestive heart failure. J Cardiovasc Pharmacol. 1987; 9(Suppl 3):S82-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351551/

266. The United States pharmacopeia, 22nd rev, and The national formulary 17th ed. Rockville, Md: The United States Pharmacopeial Convention, Inc; 1990; 1:495-6.

268. The Expert Panel (coordinated by the National Heart, Lung, and Blood Institute). Report of the Joint National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Arch Intern Med. 1988; 148:36-69. https://pubmed.ncbi.nlm.nih.gov/3422148

269. Ferguson RK, Vlasses PH, Rotmensch HH. Clinical applications of angiotensin-converting enzyme inhibitors. Am J Med. 1984; 77:690-8. https://pubmed.ncbi.nlm.nih.gov/6091446

270. Kostis JB. Angiotensin converting enzyme inhibitors. II. Clinical use. Am J Med. 1988; 116(6 Part 1):1591-1605.

271. Williams GH. Converting-enzyme inhibitors in the treatment of hypertension. N Engl J Med. 1988; 319:1517-25. https://pubmed.ncbi.nlm.nih.gov/3054561

272. Tilkemeier P, Thompson PD. Acute pancreatitis possibly related to enalapril. N Engl J Med. 1988; 318:1275-6. https://pubmed.ncbi.nlm.nih.gov/2834645

273. Cohen KR. Flushing induced by angiotensin converting enzyme inhibitor therapy. Am J Med. 1989; 86:358. https://pubmed.ncbi.nlm.nih.gov/2537568

274. Leloët X, Moore N, Deshayes P. Pseudopolymyalgia rheumatica during treatment with enalapril. BMJ. 1989; 298:325. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1835618/ https://pubmed.ncbi.nlm.nih.gov/2538177

275. Heckerling PS. Enalapril and vulvovaginal pruritus. Ann Intern Med. 1990; 112:879-80. https://pubmed.ncbi.nlm.nih.gov/2344113

276. Anon. ACE-inhibitors: contraindicated in pregnancy. WHO Drug Information. 1990; 4:23.

277. Merck & Co. Vasotec I.V. (enalaprilat) prescribing information. Whitehouse Station, NJ; 2001 Nov.

278. Thompson DF, Allen LV Jr, Stiles ML. Visual compatibility of enalaprilat with selected intravenous medications during simulated Y-site injection. Am J Hosp Pharm. 1990; 47:2530-1. https://pubmed.ncbi.nlm.nih.gov/2177585

279. Halpern NA, Colucci RD, Alicea M et al. Visual compatibility of enalaprilat with commonly used critical care medications during simulated Y-site injection. Int J Pharmacol Ther Toxicol. 1989; 27:294-7.

280. Schaaf LJ, Tremel LC, Wulf BG et al. Compatibility of enalaprilat with dobutamine, dopamine, heparin, nitroglycerin, potassium chloride and nitroprusside. J Clin Pharm Ther. 1990; 15:371-6. https://pubmed.ncbi.nlm.nih.gov/1963175

281. Kelley J, Doyle G, Donohoe J et al. The pharmacokinetic profile of enalaprilat in normal subjects and patients with renal impairment. Br J Clin Pharmacol. 1984; 274P. Abstract.

282. Kelly JG, Doyle GD, Carmody M et al. Pharmacokinetics of lisinopril, enalapril and enalaprilat in renal failure: effects of hemodialysis. Br J Clin Pharmacol. 1988; 26:781-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1386595/ https://pubmed.ncbi.nlm.nih.gov/2853960

283. Ohnishi A, Tsuboi Y, Ishizaki T et al. Kinetics and dynamics of enalapril in patients with liver cirrhosis. Clin Pharmacol Ther. 1989; 45:657-65. https://pubmed.ncbi.nlm.nih.gov/2543535

284. Baba T, Murabayashi S, Tomiyama T et al. The pharmacokinetics of enalapril in patients with compensated liver cirrhosis. Br J Clin Pharmacol. 1990; 29:766-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1380181/ https://pubmed.ncbi.nlm.nih.gov/2165799

285. Reams GP, Lal SM, Whalen JJ et al. Enalaprilat: an intravenous substitute for oral enalapril therapy–humoral and pharmacokinetic effects. J Clin Hypertens. 1986; 3:245-53.

286. Rutledge J, Ayers C, Davidson R et al. Effect of intravenous enalaprilat in moderate and severe systemic hypertension. Am J Cardiol. 1988; 62:1062-7. https://pubmed.ncbi.nlm.nih.gov/2847522

287. Tunny TJ, Nolan J, Hamlet SM et al. Effects of intravenous enalaprilat on blood pressure, renal venous and peripheral plasma renin activity and aldosterone. J Hypertens. 1986; 4(Suppl 5):S14-6.

288. DiPette DJ, Ferraro JC, Evans RR et al. Enalaprilat, an intravenous angiotensin-converting enzyme inhibitor, in hypertensive crises. Clin Pharmacol Ther. 1985; 38:199-204. https://pubmed.ncbi.nlm.nih.gov/2990798

289. Strauss R, Gavras I, Vlahakos D et al. Enalaprilat in hypertensive emergencies. J Clin Pharmacol. 1986; 26:39-43. https://pubmed.ncbi.nlm.nih.gov/3005376

290. Anon. Drugs for hypertensive emergencies. Med Lett Drugs Ther. 1989; 31:32-4. https://pubmed.ncbi.nlm.nih.gov/2927362

291. Wells TG, Bunchman TE, Kearns GL. Treatment of neonatal hypertension with enalaprilat. J Pediatr. 1990; 117:664-7. https://pubmed.ncbi.nlm.nih.gov/2170612

292. Marcadis ML, Kraus DM, Hatzopoulos FK et al. Use of enalaprilat for neonatal hypertension. J Pediatr. 1991; 119:505. https://pubmed.ncbi.nlm.nih.gov/1652634

293. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med. 1991; 325:293-302. https://pubmed.ncbi.nlm.nih.gov/2057034

294. Cohn JN, Johnson G, Ziesche S et al. A comparison of enalapril with hydralazine–isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med. 1991; 325:303-310. https://pubmed.ncbi.nlm.nih.gov/2057035

295. Braunwald E. ACE inhibitors—a cornerstone of the treatment of heart failure. N Engl J Med. 1991; 325:351-3. https://pubmed.ncbi.nlm.nih.gov/2057038

296. Joint letter of Bristol-Myers Squibb Company; Ciba-Geigy Corporation, Pharmaceutical Division; Hoechst-Roussel Pharmaceuticals Inc; ICI Pharmaceutical Group, ICI Americas Inc; Merck Human Health Division; Parke-Davis, Division of Warner-Lambert Company. Important warning information regarding use of ACE inhibitors in pregnancy. 1992 Mar 16.

297. US Food and Drug Administration. Dangers of ACE inhibitors during second and third trimesters of pregnancy. FDA Med Bull. 1992; 22:2.

298. The SOLVD Investigators. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med. 1992; 327:685-91. https://pubmed.ncbi.nlm.nih.gov/1463530

299. Cohn JN. The prevention of heart failure—a new agenda. N Engl J Med. 1992; 327:725-7. https://pubmed.ncbi.nlm.nih.gov/1495526

300. Swedberg K, Held P, Kjekshus J et al. Effects of the early administration of enalapril on mortality in patients with acute myocardial infarction: results of the Cooperative New Scandinavian enalapril survival study II (Consensus II). N Engl J Med. 1992; 327:678-84. https://pubmed.ncbi.nlm.nih.gov/1495520

301. Kjekshus J, Swedberg K, Snappin S. Effects of enalapril on long-term mortality in severe congestive heart failure. Am J Cardiol. 1992; 69:103-7. https://pubmed.ncbi.nlm.nih.gov/1729857

302. US Food and Drug Administration. Severe allergic reactions associated with dialysis and ACE inhibitors. FDA Med Bull. 1992; 22:4.

303. Piper JM, Ray WA, Rosa FW. Pregnancy outcome following exposure to angiotensin-converting enzyme inhibitors. Obstet Gynecol. 1992; 80:429-32. https://pubmed.ncbi.nlm.nih.gov/1495700

304. Parnes EL, Shapiro WB. Anaphylactoid reactions in hemodialysis patients treated with the AN69 dialyzer. Kidney Int. 1991; 40:1148-52. https://pubmed.ncbi.nlm.nih.gov/1762316

305. Scott AA, Purohit DM. Neonatal renal failure: a complication of maternal antihypertensive therapy. Am J Obstet Gynecol. 1989; 160:1223-4. https://pubmed.ncbi.nlm.nih.gov/2543224

306. Tielemans C, Madhoun P, Lenaers M et al. Anaphylactoid reactions during hemodialysis on AN69 membranes in patients receiving ACE inhibitors. Kidney Int. 1990; 38:982-4. https://pubmed.ncbi.nlm.nih.gov/2266684

307. Pfeffer MA, Braunwald E, Moyé LA et al for the SAVE Investigators Group. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction: results of the Survival and Ventricular Enlargement Trial. N Engl J Med. 1992; 327:669-77. https://pubmed.ncbi.nlm.nih.gov/1386652

308. Sharpe N, Smith H, Murphy J et al. Early prevention of left ventricular dysfunction after myocardial infarction with angiotensin-converting-enzyme inhibition. Lancet. 1991; 337:872-6. https://pubmed.ncbi.nlm.nih.gov/1672967

309. Oldroyd KG, Pye MP, Ray SG et al. Effects of early captopril administration on infarct expansion, left ventricular remodeling and exercise capacity after acute myocardial infarction. Am J Cardiol. 1991; 68:713-8. https://pubmed.ncbi.nlm.nih.gov/1892076

310. Sharpe N, Murphy J, Smith H et al. Treatment of patients with symptomless left ventricular dysfunction after myocardial infarction. Lancet. 1988; 1:255-9. https://pubmed.ncbi.nlm.nih.gov/2893080

311. Pfeffer MA, Lamas GA, Vaughan DE et al. Effect of captopril on progressive ventricular dilatation after anterior myocardial infarction. N Engl J Med. 1988; 319:80-6. https://pubmed.ncbi.nlm.nih.gov/2967917

313. Weber MA, Laragh JH. Hypertension: steps forward and steps backward: the Joint National Committee fifth report. Arch Intern Med. 1993; 153:149-52. https://pubmed.ncbi.nlm.nih.gov/8422205

314. Alderman MH. Which antihypertensive drugs first—and why! JAMA. 1992; 267:2786-7. Editorial.

315. Baker DW, Konstam MA, Bottorff M. Management of heart failure. JAMA. 1994; 272:1361-6. https://pubmed.ncbi.nlm.nih.gov/7933398

316. Young JB. Angiotensin-converting enzyme inhibitors in heart failure: new strategies justified by recent clinical trials. Int J Cardiol. 1994; 43:151-63. https://pubmed.ncbi.nlm.nih.gov/8181869

317. Sharpe N. ACE inhibitors versus diuretics: when to choose which drug? Cardiovasc Drugs Ther. 1993; 7:877-9. Abstract.

318. Riegger GAJ. The effects of ACE inhibitors on exercise capacity in the treatment of congestive heart failure. J Cardiovasc Pharmacol. 1990; 15(Suppl 2):S41-6.

319. Agishi T. Anion-blood contact reaction (ABC reaction) in patients treated by LDL apheresis with dextran sulfate–cellulose column while receiving ACE inhibitors. JAMA. 1994; 271:195-6. https://pubmed.ncbi.nlm.nih.gov/7695665

320. Olbricht CJ, Schaumann D, Fischer D. Anaphylactoid reactions, LDL apheresis with dextran sulphate, and ACE inhibitors. Lancet. 1992; 340:908-9. https://pubmed.ncbi.nlm.nih.gov/1357312

321. Keller C, Grützmacher P, Bahr F et al. LDL-apheresis with dextran sulphate and anaphylactoid reactions to ACE inhibitors. Lancet. 1993; 341:60-1. https://pubmed.ncbi.nlm.nih.gov/8093314

322. McNeil. Motrin (ibuprofen suspension, chewable tablets, caplets) prescribing information. Fort Washington, PA; 1994 Dec.

323. Abe K, Ito T, Sato M et al. Role of prostaglandin in the antihypertensive mechanism of captopril in low renin hypertension. Clin Sci. 1980; 59:141-4s.

324. Angiotensin-converting enzyme inhibitor interactions: nonsteroidal anti-inflammatory drugs (NSAIDSs). In Hansten PD, Horn JR. Drug interactions and updates. Vancouver, WA: Applied Therapeutics, Inc; 1993:131-2.

325. ACE inhibitors/indomethacin. In: Tatro DS, Olin BR, Hebel SK et al. Drug interaction facts. St. Louis: JB Lippincott Co; 1992(April):28.

326. Salvetti A, Abdel-Haq B, Magagna A et al. Indomethacin reduces the antihypertensive action of enalapril. Clin Exp Hypertens. 1987; 9:559-67.

327. Fujita T, Yamashita N, Yamashita K. Effect of indomethacin on antihypertensive action of captopril in hypertensive patients. Clin Exp Hypertens. 1981; 3:939-52. https://pubmed.ncbi.nlm.nih.gov/7026199

328. Moore TJ, Crantz FR, Hollenberg NK et al. Contribution of prostaglandins to the antihypertensive action of captopril in essential hypertension. Hypertension. 1981; 3:168-73. https://pubmed.ncbi.nlm.nih.gov/6260645

329. Silberbauer K, Stanek B, Templ H. Acute hypotensive effect of captopril in man modified by prostaglandin synthesis inhibition. Br J Clin Pharmacol. 1982; 14(Suppl 2):87-93S.

330. Seelig CB, Maloley PA, Campbell JR. Nephrotoxicity associated with concomitant ACE inhibitor and NSAID therapy. South Med J. 1990; 83:1144-8. https://pubmed.ncbi.nlm.nih.gov/2218652

331. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico. GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Lancet. 1994; 343:1115-22. https://pubmed.ncbi.nlm.nih.gov/7910229

332. Ambrosioni E, Borghi C, Magnani B for the Survival of Myocardial Infarction Long-Term Evaluation (SMILE) Study Investigators. The effect of the angiotensin-converting-enzyme inhibitor zofenopril on mortality and morbidity after anterior myocardial infarction. N Engl J Med. 1995; 332:80-5. https://pubmed.ncbi.nlm.nih.gov/7990904

333. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet. 1993; 342:821-8. https://pubmed.ncbi.nlm.nih.gov/8104270

334. Ball SG, Hall AS, Murray GD. Angiotensin-converting enzyme inhibitors after myocardial infarction: indications and timing. J Am Coll Cardiol. 1995; 25(Suppl):42-6S.

335. ISIS-4 Collaborative Group. Fourth international study of infarct survival: protocol for a large simple study of the effects of oral mononitrate, of oral captopril, and of intravenous magnesium. Am J Cardiol. 1991; 68:87-100D.

336. Simoons ML. Myocardial infarction: ACE inhibitors for all? for ever? Lancet. 1994; 344:279-81. Editorial.

337. Anon. An ACE inhibitor after a myocardial infarction. Med Lett Drugs Ther. 1994; 36:69-70. https://pubmed.ncbi.nlm.nih.gov/8035753

338. Ertl G, Jugdutt B. ACE inhibition after myocardial infarction: can megatrials provide answers? Lancet. 1994; 344:1068-9.

339. Ertl G. Angiotensin converting enzyme inhibitors in angina and myocardial infarction: what role will they play in the 1990s? Drugs. 1993; 46:209-18.

340. Purcell H, Coats A, Fox K et al. Improving outcome after acute myocardial infarction: what is the role of ACE inhibitors? Br J Clin Pract. 1995; 49:195-9. (IDIS 349780)

341. Ball SG, Hall AS. What to expect from ACE inhibitors after myocardial infarction. Br Heart J. 1994; 72(Suppl):S70-4.

342. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58 050 patients with suspected acute myocardial infarction. Lancet. 1995; 345:669-85. https://pubmed.ncbi.nlm.nih.gov/7661937

343. Chinese Cardiac Study Collaborative Group. Oral captopril versus placebo among 13 634 patients with suspected acute myocardial infarction: interim report from the Chinese Cardiac Study (CCS-1). Lancet. 1995; 345:686-7. https://pubmed.ncbi.nlm.nih.gov/7885123

344. National Heart, Lung, and Blood Institute. NHLBI panel reviews safety of calcium channel blockers. Rockville, MD; 1995 Aug 31. Press release.

345. National Heart, Lung, and Blood Institute. New analysis regarding the safety of calcium-channel blockers: a statement for health professionals from the National Heart, Lung, and Blood Institute. Rockville, MD; 1995 Sep 1.

346. Psaty BM, Heckbert SR, Koepsell TD et al. The risk of myocardial infarction associated with antihypertensive drug therapies. JAMA. 1995; 274:620-5. https://pubmed.ncbi.nlm.nih.gov/7637142

347. Yusuf S. Calcium antagonists in coronary artery disease and hypertension: time for reevaluation? Circulation. 1995; 92:1079-82. Editorial.

348. Vaseretic (enalapril maleate–hydrochlorothiazide) tablets prescribing information. In: Physicians’ desk reference. 50th ed. Montvale, NJ: Medical Economics Company Inc; 1996 (Suppl A):A121-2.

349. Merck & Co. Vasotec I.V. (enalaprilat) prescribing information. In: Physicians; desk reference. 50th ed. Montvale, NJ: Medical Economics Company Inc; 1996 (Suppl A):A122.

350. Hoechst Marion Roussel, Inc. Teczem (enalapril maleate/diltiazem malate) extended release tablets prescribing information. Kansas City, MO; 1996 July.

352. Kaplan NM. Choice of initial therapy for hypertension. JAMA. 1996; 275:1577-80. https://pubmed.ncbi.nlm.nih.gov/8622249

353. Psaty BM, Smith NL, Siscovich DS et al. Health outcomes associated with antihypertensive therapies used as first-line agents: a systematic review and meta-analysis. JAMA. 1997; 277:739-45. https://pubmed.ncbi.nlm.nih.gov/9042847

355. Garg R, Yusuf S for the Collaborative Group on ACE Inhibitor Trials. Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. JAMA. 1995; 273:1450-6. https://pubmed.ncbi.nlm.nih.gov/7654275

356. Lewis EJ, Hunsicker LG, Bain RP et al for the Collaborative Study Group. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med. 1993; 329:1456-62. https://pubmed.ncbi.nlm.nih.gov/8413456

357. Klahr S, Levey AS, Beck GJ et al for the Modification of Diet in Renal Disease Study Group. The effects of dietary protein restriction and blood pressure control on the progression of chronic renal disease. N Engl J Med. 1994; 330:877-84. https://pubmed.ncbi.nlm.nih.gov/8114857

358. Maschio G, Alberti D, Jannin G et al for the Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group. Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. N Engl J Med. 1996; 334:939-45. https://pubmed.ncbi.nlm.nih.gov/8596594

359. Giatras I, Lau J, Levey AS et al for the Angiotensin-Converting Enzyme Inhibition in Progressive Renal Insufficiency Study Group. Effect of angiotensin-converting enzyme inhibitors on the progression of nondiabetic renal disease: a meta-analysis of randomized trials. Ann Intern Med. 1997; 127:337-45. https://pubmed.ncbi.nlm.nih.gov/9273824

360. American College of Cardiology and American Heart Association. ACC/AHA guidelines for the evaluation and management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Evaluation and Management of Heart Failure). Circulation. 1995; 92:2764-84. https://pubmed.ncbi.nlm.nih.gov/7586389

361. Bristol-Myers Squibb Company. Capoten (captopril) tablets prescribing information (J4-458F). In: Physicians’ desk reference. 51st ed. Montvale, NJ: Medical Economics Company Inc; 1997:740-4.

362. Jenkins AC, Dreslinski GR, Tadros SS et al. Captopril in hypertension: seven years later. J Cardiovasc Pharmacol. 1985; 7(Suppl 1):S96-101. https://pubmed.ncbi.nlm.nih.gov/2580185

363. Hommel E, Parving HH, Mathiesen E et al. Effect of captopril on kidney function in insulin-dependent diabetic patients with nephropathy. BMJ. 1986; 293:467-70. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1341107/ https://pubmed.ncbi.nlm.nih.gov/3091164

364. Bjorck S, Nyberg G, Mulec H et al. Beneficial effects of angiotensin converting enzyme inhibition on renal function in patients with diabetic nephropathy. BMJ. 1986; 293:471-4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1341108/ https://pubmed.ncbi.nlm.nih.gov/3017501

365. O’Hare JA. Captopril and diabetic proteinuria: a correction. N Engl J Med. 1987; 316:52. https://pubmed.ncbi.nlm.nih.gov/3785349

366. Remuzzi G, Ruggenenti P. Slowing the progression of diabetic nephropathy. N Engl J Med. 1993; 329:1496-7. https://pubmed.ncbi.nlm.nih.gov/8413463

367. Bakris GL. Angiotensin-converting enzyme inhibitors and progression of diabetic nephropathy. Ann Intern Med. 1993; 118:643-4. https://pubmed.ncbi.nlm.nih.gov/8452332

368. Fournier A, Lalau JD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med. 1994; 330:937. https://pubmed.ncbi.nlm.nih.gov/8114873

369. Björck S, Mulec H, Johnsen SA et al. Renal protective effect of enalapril in diabetic nephropathy. BMJ. 1992; 304:339-43. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1881212/ https://pubmed.ncbi.nlm.nih.gov/1540729

370. Whelton PK, Appel LJ, Espeland MA et al. for the TONE Collaborative Research Group. Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomized controlled trial of nonpharmacologic interventions in the elderly (TONE). JAMA. 1998; 279:839-46. https://pubmed.ncbi.nlm.nih.gov/9515998

371. Hoechst Marion Roussel, Inc. Teczem (enalapril maleast/diltiazem malate) extended release tablets prescribing information. Kansas City, MO; 1996 July.

373. Gradman AH, Cutler NR, Davis PJ et al. Combined enalapril and felodipine extended release (ER) for systemic hypertension. Am J Cardiol. 1997; 9:431-5.

374. Hoechst Marion Roussel, Kansas City, MO: Personal communication on diltiazem 24:28.92.

375. Pitt B, Zannad F, Remme WJ et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med. 1999; 341(10):709-17. https://pubmed.ncbi.nlm.nih.gov/10471456

376. The RALES Investigators. Effectiveness of spironolactone added to an angiotensin-converting enzyme inhibitor and a loop diuretic for severe chronic congestive heart failure (the randomized aldosterone evaluation study [RALES]). Am J Cardiol. 1996; 78:902-7. https://pubmed.ncbi.nlm.nih.gov/8888663

377. Zannad F. Angiotensin-converting enzyme inhibitor and spironolactone combination therapy: new objectives in congestive heart failure treatment. Am J Cardiol. 1993; 71:34A-9A. https://pubmed.ncbi.nlm.nih.gov/8422003

378. Dahlstrom U, Karlsson E. Captopril and spironolactone therapy for refractory congestive heart failure. Am J Cardiol. 1993; 71:29A-33A. https://pubmed.ncbi.nlm.nih.gov/8422001

379. Anon. Consensus recommendations for the management of chronic heart failure. On behalf of the membership of the advisory council to improve outcomes nationwide in heart failure. Part II. Management of heart failure: approaches to the prevention of heart failure. Am J Cardiol. 1999; 83:9A-38A.

380. American Diabetes Association. Clinical Practice Recommendations 2003. Position Statement. Diabetic nephropathy. Diabetes Care. 2003; 26(Suppl 1):S94-8.

381. Weber KT. Aldosterone and spironolactone in heart failure. N Engl J Med. 1999; 341:753-4. https://pubmed.ncbi.nlm.nih.gov/10471464

382. Genuth P. United Kingdom prospective diabetes study results are in. J Fam Pract. 1998; 47:(Suppl 5):S27.

383. Watkins PJ. UKPDS: a message of hope and a need for change. Diabet Med. 1998; 15:895-6. https://pubmed.ncbi.nlm.nih.gov/9827842

384. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998; 317:703-13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC28659/ https://pubmed.ncbi.nlm.nih.gov/9732337

385. Bretzel RG, Voit K, Schatz H et al. The United Kingdom Prospective Diabetes Study (UKPDS): implications for the pharmacotherapy of type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes. 1998; 106:369-72. https://pubmed.ncbi.nlm.nih.gov/9831300

386. Struthers AD. Aldosterone excape during angiotensin-convering enzyme inhibitor therapy in chronic heart failure. J Card Fail. 1996; 2:47-54. https://pubmed.ncbi.nlm.nih.gov/8798105

387. Tatti P, Pahor M, Byington RP et al. Outcome results of the fosinopril versus amlodipine cardiovascular events randomized trial (FACET) in patients with hypertension and NIDDM. Diabetes Care. 1998; 21:597-603. https://pubmed.ncbi.nlm.nih.gov/9571349

388. Staessen J, Lijnen P, Fagard R et al. Rise in plasma concentration of aldosterone during long-term angiotensin II suppression. J Endocr. 1981; 91:457-65. https://pubmed.ncbi.nlm.nih.gov/7035596

389. MacFadyen RJ, Lee AF, Morton JJ et al. How often are angiotensin II and aldosterone concentrations raised during chronic ACE inhibitor treatment in cardiac failure? Heart. 1999; 82:57-61.

390. Struthers AD. Why does spironolactone improve mortality over and above and ACE inhibitor in congestive heart failure? Br J Clin Pharmacol. 1999; 47:479-82.

391. Anon. Spironolactone for heart failure. Med Lett Drugs Ther. 1999; 41:81-2. https://pubmed.ncbi.nlm.nih.gov/10505071

392. Weiner B, Braus DM, Clifton GD et al. ASHP therapeutic guidelines on angiotensin-converting-enzyme inhibitors in patients with left ventricular dysfunction. Am J Health-Syst Pharm. 1997; 54:299-313. https://pubmed.ncbi.nlm.nih.gov/9028424

393. UK Prospective Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of marcrovascular and microvascular complications in type 2 diabetes: UKPDS 39. BMJ. 1998; 317:713-20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC28660/ https://pubmed.ncbi.nlm.nih.gov/9732338

394. Davis TM. United Kingdom Prospective Diabetes Study: the end of the beginning? Med J Aust. 1998; 169:511-2.

397. Pitt B. “Escape” of aldosterone production in patients with left ventricular dysfunction treated with angiotensin converting enzyme inhibitor: implications for therapy. Cardiovasc Drugs Ther. 1995; 9:145-9. https://pubmed.ncbi.nlm.nih.gov/7786835

398. Aspirin interactions: captopril. In: Hansten PD, Horn JR. Drug interactions and updates. Vancouver, WA: Applied Therapeutics, Inc; 1997:62-3.

399. Packer M, Poole-Wilson PA, Armstrong PW et al. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. Circulation. 1999; 100:2312-8. https://pubmed.ncbi.nlm.nih.gov/10587334

400. American Diabetes Association. The United Kingdom Prospective Diabetes Study (UKPDS) for type 2 diabetes: what you need to know about the results of a long-term study. Washington, DC; 1998 Sep 15 from American Diabetes Association web site. http://www.diabetes.org

401. Izzo JL, Levy D, Black HR. Importance of systolic blood pressure in older Americans. Hypertension. 2000; 35:1021-4. https://pubmed.ncbi.nlm.nih.gov/10818056

402. Frohlich ED. Recognition of systolic hypertension for hypertension. Hypertension. 2000; 35:1019-20. https://pubmed.ncbi.nlm.nih.gov/10818055

403. Latini R, Tognoni G, Maggioni AP et al. Clinical effects of early angiotensin-converting enzyme inhibitor treatment for acute myocardial infarction are similar in the presence and absence of aspirin. J Am Coll Cardiol. 2000; 35:1801-7. https://pubmed.ncbi.nlm.nih.gov/10841227

404. Hall D. The aspirin-angiotensin-converting enzyme inhibitor tradeoff: to halve and halve not. J Am Coll Cardiol. 2000; 35:1808-12. https://pubmed.ncbi.nlm.nih.gov/10841228

405. Bakris GL, Williams M, Dworkin L et al. Preserving renal function in adults with hypertension and diabetes: A consensus approach. Am J Kidney Dis. 2000; 36:646-61. https://pubmed.ncbi.nlm.nih.gov/10977801

406. Hansson L, Zanchetti A, Carruthers SG et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet. 1998; 351:1755-62. https://pubmed.ncbi.nlm.nih.gov/9635947

407. Food and Drug Administration. Lexxel (enalapril maleate/felodipine ER) tablets [July 18, 2000: AstraZeneca]. MedWatch drug labeling changes. Rockville, MD; July 2000. From FDA web site. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts

408. Paddock Laboratories. Ora-Sweet SF oral syrup material safety data sheet. Minneapolis, MN; 1992 Jan 31.

409. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 2003; 26(Suppl 1):S33-50.

410. Schoolwerth AC, Sica DA, Ballermann BJ et al. Renal considerations in angiotensin converting enzyme inhibitor therapy: a statement for healthcare professionals from the Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association. Circulation. 2001; 104:1985-91. https://pubmed.ncbi.nlm.nih.gov/11602506

411. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care. 2003; 26(Suppl. 1):S80-2.

412. Heart Outcomes Prevention Evaluation (HOPE) Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet. 2000; 355: 253-9.

413. Niskanen L, Hender T, Hansson L et al. Reduced cardiovascular morbidity and mortality in hypertensive diabetic patients on first-line therapy with an ACE inhibitor compared with a diuretic/β-blocker-based treatment regimen. Diabetes Care. 2001; 24:2091-6. https://pubmed.ncbi.nlm.nih.gov/11723089

414. Williams MA, Fleg JL, Ades PA et al. Secondary prevention of coronary heart disease in the elderly (with emphasis on patients ≥ 75 years of age). An American Heart Association Scientific Statement from the Council on Clinical Cardiology Subcommittee on Exercise, Cardiac Rehabilitation, and Prevention. Circulation. 2002; 105:1735-43. https://pubmed.ncbi.nlm.nih.gov/11940556

415. Williams CL, Hayman LL, Daniels SR et al. Cardiovascular health in childhood: a statement for health professional from the Committee on Atherosclerosis, Hypertension, and Obesity in the Young (AHOY) of the Council on Cardiovascular Disease in the Young, American Heart Association. Circulation. 2002; 106:143-60. https://pubmed.ncbi.nlm.nih.gov/12093785

416. Hunt SA, Baker DW, Chin MH et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). 2001. Available from website. Accessed July 25, 2002. http://www.cardiosource.org/Science-And-Quality/Practice-Guidelines-and-Quality-Standards.aspx

419. Appel LJ. The verdict from ALLHAT—thiazide diuretics are the preferred initial therapy for hypertension. JAMA. 2002; 288:3039-60. https://pubmed.ncbi.nlm.nih.gov/12479770

420. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002; 288:2981-97. https://pubmed.ncbi.nlm.nih.gov/12479763

422. Douglas JG, Bakris GL, Epstein M et al. Management of high blood pressure in African Americans: Consensus statement of the Hypertension in African Americans Working Group of the International Society on Hypertension in Blacks. Arch Intern Med. 2003; 163:525-41.

424. The Guidelines Subcommitee of the WHO/ISH Mild Hypertension Liaison Committee. 1999 guidelines for the management of hypertension. J Hypertension. 1999; 17:392-403.

425. Bauer JH, Reams GP. Antihypertensive treatment in patients with renal disease: control of glomerular hypertension. Kidney. (in press)

426. MacGregor GA, Markandu ND, Banks RA et al. Captopril in essential hypertension; contrasting effects of adding hydrochlorothiazide or propranolol. BMJ. 1982; 284:693-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1496699/ https://pubmed.ncbi.nlm.nih.gov/6802291

427. Hricik DE. Captopril-induced renal insufficiency. Ann Intern Med. 1986; 104:126. https://pubmed.ncbi.nlm.nih.gov/3510053

428. The Captopril-Digoxin Multicenter Research Group. Comparative effects of therapy with captopril and digoxin in patients with mild to moderate heart failure. JAMA. 1988; 259:539-44. https://pubmed.ncbi.nlm.nih.gov/2447297

429. Neal B, MacMahon S, Chapman N. Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs. Lancet. 2000;356:1955-64.

430. Cushman WC, Ford CE, Cutler JA, et al. Success and predictors of blood pressure control in diverse North American settings: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). J Clin Hypertens (Greenwich). 2002;4:393-404.

431. Black HR, Elliott WJ, Neaton JD et al. Baseline characteristics and elderly blood pressure control in the CONVINCE trial. Hypertension. 2001; 37:12-18. https://pubmed.ncbi.nlm.nih.gov/11208750

432. Black HR, Elliott WJ, Grandits G, et al. Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial. JAMA. 2003;289:2073-2082.

433. Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint Reduction in Hypertension Study (LIFE). Lancet. 2002;359:995-1003.

434. The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000;342:145-153.

435. PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack. Lancet. 2001;358:1033-41.

436. Wing LMH, Reid CM, Ryan P, et al, for Second Australian National Blood Pressure Study Group. A comparison of outcomes with angiotensin-converting-enzyme inhibitors and diuretics for hypertension in the elderly. N Engl J Med. 2003;348:583-92.

437. Packer M, Coats AJ, Fowler MB, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001;344:1651-58.

438. CIBIS Investigators and Committees. A randomized trial of beta-blockade in heart failure: the Cardiac Insufficiency Bisoprolol Study (CIBIS). Circulation. 1994;90:1765-1773.

439. Kober L, Torp-Pedersen C, Carlsen JE, et al, for Trandolapril Cardiac Evaluation (TRACE) Study Group. A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 1995;333:1670-6.

440. Hager WD, Davis BR, Riba A, et al, for the Survival and Ventricular Enlargement (SAVE) Investigators. Absence of a deleterious effect of calcium channel blockers in patients with left ventricular dysfunction after myocardial infarction: the SAVE Study Experience. Am Heart J. 1998;135:406-13.

441. Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348:1309-1321.

443. Tepper D. Frontiers in congestive heart failure: effect of metoprolol CR/XL in chronic heart failure: MetoprololCR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF). Congest Heart Fail. 1999;5:184-5.

444. β-Blocker Heart Attack Trial Research Group. A randomized trial of propranolol in patients with acute myocardial infarction: I. Mortality results. JAMA. 1982; 247:1707-14. https://pubmed.ncbi.nlm.nih.gov/7038157

445. The Capricorn Investigators. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the Capricorn randomized trial. Lancet. 2001; 357:1385-90. https://pubmed.ncbi.nlm.nih.gov/11356434

446. Cohn JN, Tognoni GA. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001; 345:1667-75. https://pubmed.ncbi.nlm.nih.gov/11759645

447. Reviewers’ comments (personal observations) on the Thiazides General Statement 40:28.

448. Exner DV, Dries DL, Domanski MJ et al. Lesser response to angiotensin-converting-enzyme inhibitor therapy in black as compared with white patients with left ventricular dysfunction. N Engl J Med. 2001; 344:1351-7. https://pubmed.ncbi.nlm.nih.gov/11333991

450. Wright JT, Dunn JK, Cutler JA et al. Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril. JAMA. 2005; 293:1595-607 https://pubmed.ncbi.nlm.nih.gov/15811979

451. Neaton JD, Kuller LH. Diuretics are color blind. JAMA. 2005; 293:1663-6. https://pubmed.ncbi.nlm.nih.gov/15811986

452. Parke Davis. Accupril (quinapril hydrochloride) tablets prescribing information. New York, NY; 2003 Feb.

453. Cooper WO, Hernandez-Diaz S, Arbogast PG et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med. 2006; 354:2443-51. https://pubmed.ncbi.nlm.nih.gov/16760444

454. Food and Drug Administration. FDA public health advisory: angiotensin-converting enzyme inhibitor (ACE inhibitor) drugs and pregnancy. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/PublicHealthAdvisories/ucm053113.htm

455. Biovail Pharmaceutics. Vaseretic (enalapril maleate and hydrochlorothiazide) tablets prescribing information. Bridgewater, NJ; 2008 Mar. From the DailyMed website. Accessed Oct 3, 2008. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=8353

456. National Kidney Foundation Guideline. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Kidney Disease Outcome Quality Initiative. Am J Kidney Dis. 2002; 39(Suppl 2):S1-246.

501. James PA, Oparil S, Carter BL et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014; 311:507-20. https://pubmed.ncbi.nlm.nih.gov/24352797

502. Mancia G, Fagard R, Narkiewicz K et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013; 31:1281-357. https://pubmed.ncbi.nlm.nih.gov/23817082

503. Go AS, Bauman MA, Coleman King SM et al. An effective approach to high blood pressure control: a science advisory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention. Hypertension. 2014; 63:878-85. https://pubmed.ncbi.nlm.nih.gov/24243703

504. Weber MA, Schiffrin EL, White WB et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens (Greenwich). 2014; 16:14-26. https://pubmed.ncbi.nlm.nih.gov/24341872

505. Wright JT, Fine LJ, Lackland DT et al. Evidence supporting a systolic blood pressure goal of less than 150 mm Hg in patients aged 60 years or older: the minority view. Ann Intern Med. 2014; 160:499-503. https://pubmed.ncbi.nlm.nih.gov/24424788

506. Mitka M. Groups spar over new hypertension guidelines. JAMA. 2014; 311:663-4. https://pubmed.ncbi.nlm.nih.gov/24549531

507. Peterson ED, Gaziano JM, Greenland P. Recommendations for treating hypertension: what are the right goals and purposes?. JAMA. 2014; 311:474-6. https://pubmed.ncbi.nlm.nih.gov/24352710

508. Bauchner H, Fontanarosa PB, Golub RM. Updated guidelines for management of high blood pressure: recommendations, review, and responsibility. JAMA. 2014; 311:477-8. https://pubmed.ncbi.nlm.nih.gov/24352759

510. Staessen JA, Fagard R, Thijs L et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet. 1997; 350:757-64. https://pubmed.ncbi.nlm.nih.gov/9297994

511. JATOS Study Group. Principal results of the Japanese trial to assess optimal systolic blood pressure in elderly hypertensive patients (JATOS). Hypertens Res. 2008; 31:2115-27. https://pubmed.ncbi.nlm.nih.gov/19139601

515. Thomas G, Shishehbor M, Brill D et al. New hypertension guidelines: one size fits most?. Cleve Clin J Med. 2014; 81:178-88. https://pubmed.ncbi.nlm.nih.gov/24591473

518. SPS3 Study Group, Benavente OR, Coffey CS et al. Blood-pressure targets in patients with recent lacunar stroke: the SPS3 randomised trial. Lancet. 2013; 382:507-15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3979302/ https://pubmed.ncbi.nlm.nih.gov/23726159

520. American Diabetes Association. Standards of medical care in diabetes--2014. Diabetes Care. 2014; 37 Suppl 1:S14-80.

521. ACCORD Study Group, Cushman WC, Evans GW et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010; 362:1575-85. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123215/ https://pubmed.ncbi.nlm.nih.gov/20228401

522. Patel A, ADVANCE Collaborative Group, MacMahon S et al. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet. 2007; 370:829-40. https://pubmed.ncbi.nlm.nih.gov/17765963

523. Fihn SD, Gardin JM, Abrams J et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2012; 126:e354-471.

524. WRITING COMMITTEE MEMBERS, Yancy CW, Jessup M et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013; 128:e240-327.

525. Smith SC, Benjamin EJ, Bonow RO et al. AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients with Coronary and other Atherosclerotic Vascular Disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation. Circulation. 2011; 124:2458-73. https://pubmed.ncbi.nlm.nih.gov/22052934

526. Kernan WN, Ovbiagele B, Black HR et al. Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2014; :. https://pubmed.ncbi.nlm.nih.gov/24788967

527. O'Gara PT, Kushner FG, Ascheim DD et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013; 127:e362-425. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3695607/

528. Pfeffer MA, Swedberg K, Granger CB et al. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet. 2003; 362:759-66. https://pubmed.ncbi.nlm.nih.gov/13678868

530. Myers MG, Tobe SW. A Canadian perspective on the Eighth Joint National Committee (JNC 8) hypertension guidelines. J Clin Hypertens (Greenwich). 2014; 16:246-8. https://pubmed.ncbi.nlm.nih.gov/24641124

531. . Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators. Lancet. 2000; 355:253-9. https://pubmed.ncbi.nlm.nih.gov/10675071

534. Qaseem A, Hopkins RH, Sweet DE et al. Screening, monitoring, and treatment of stage 1 to 3 chronic kidney disease: A clinical practice guideline from the American College of Physicians. Ann Intern Med. 2013; 159:835-47. https://pubmed.ncbi.nlm.nih.gov/24145991

535. Taler SJ, Agarwal R, Bakris GL et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for management of blood pressure in CKD. Am J Kidney Dis. 2013; 62:201-13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929429/ https://pubmed.ncbi.nlm.nih.gov/23684145

536. Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int Suppl. 2012: 2: 337-414.

537. Levey AS, de Jong PE, Coresh J et al. The definition, classification, and prognosis of chronic kidney disease: a KDIGO Controversies Conference report. Kidney Int. 2011; 80:17-28. https://pubmed.ncbi.nlm.nih.gov/21150873

541. Perk J, De Backer G, Gohlke H et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J. 2012; 33:1635-701. https://pubmed.ncbi.nlm.nih.gov/22555213

542. Marik PE, Varon J. Hypertensive crises: challenges and management. Chest. 2007; 131:1949-62. https://pubmed.ncbi.nlm.nih.gov/17565029

543. National Kidney Foundation Kidney Disease Outcomes Quality Initiative. K/DOQI Clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease (2002). From National Kidney Foundation website. http://www.kidney.org/professionals/kdoqi/guidelines_commentaries.cfm

600. Valeant. Vasotec (enalapril maleate) tablets prescribing information. Bridgewater, NJ; 2012 Sep.

601. Hospira. Enalaprilat injection prescribing information. Lake Forest, IL; 2010 Mar.

700. Yancy CW, Jessup M, Bozkurt B et al. 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2016; 134:e282-93.

701. Ponikowski P, Voors AA, Anker SD et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016; 37:2129-200. https://pubmed.ncbi.nlm.nih.gov/27206819

702. McMurray JJ, Packer M, Desai AS et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014; 371:993-1004. https://pubmed.ncbi.nlm.nih.gov/25176015

703. Ansara AJ, Kolanczyk DM, Koehler JM. Neprilysin inhibition with sacubitril/valsartan in the treatment of heart failure: mortality bang for your buck. J Clin Pharm Ther. 2016; 41:119-27. https://pubmed.ncbi.nlm.nih.gov/26992459

704. Jong P, Yusuf S, Rousseau MF et al. Effect of enalapril on 12-year survival and life expectancy in patients with left ventricular systolic dysfunction: a follow-up study. Lancet. 2003; 361:1843-8. https://pubmed.ncbi.nlm.nih.gov/12788569

705. Reed BN, Sueta CA. Stage B: what is the evidence for treatment of asymptomatic left ventricular dysfunction?. Curr Cardiol Rev. 2015; 11:18-22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4347204/ https://pubmed.ncbi.nlm.nih.gov/24251458

706. Massie BM. Aspirin use in chronic heart failure: what should we recommend to the practitioner?. J Am Coll Cardiol. 2005; 46:963-6. https://pubmed.ncbi.nlm.nih.gov/16168276

803. Lamas GA, Escolar E, Faxon DP. Examining treatment of ST-elevation myocardial infarction: the importance of early intervention. J Cardiovasc Pharmacol Ther. 2010; 15:6-16. https://pubmed.ncbi.nlm.nih.gov/20061507

805. Reed GW, Rossi JE, Cannon CP. Acute myocardial infarction. Lancet. 2017; 389:197-210. https://pubmed.ncbi.nlm.nih.gov/27502078

1100. Amsterdam EA, Wenger NK, Brindis RG et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014; 130:e344-426. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4676081/

1150. Flynn JT, Kaelber DC, Baker-Smith CM et al. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics. 2017; 140 https://pubmed.ncbi.nlm.nih.gov/28827377

1200. Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018; 71:el13-e115. https://pubmed.ncbi.nlm.nih.gov/29133356

1201. Bakris G, Sorrentino M. Redefining hypertension - assessing the new blood-pressure guidelines. N Engl J Med. 2018; 378:497-499. https://pubmed.ncbi.nlm.nih.gov/29341841

1202. Carey RM, Whelton PK, 2017 ACC/AHA Hypertension Guideline Writing Committee. Prevention, detection, evaluation, and management of high blood pressure in adults: synopsis of the 2017 American College of Cardiology/American Heart Association hypertension guideline. Ann Intern Med. 2018; 168:351-358. https://pubmed.ncbi.nlm.nih.gov/29357392

1207. Burnier M, Oparil S, Narkiewicz K et al. New 2017 American Heart Association and American College of Cardiology guideline for hypertension in the adults: major paradigm shifts, but will they help to fight against the hypertension disease burden?. Blood Press. 2018; 27:62-65. https://pubmed.ncbi.nlm.nih.gov/29447001

1209. Qaseem A, Wilt TJ, Rich R et al. Pharmacologic treatment of hypertension in adults aged 60 years or older to higher versus lower blood pressure targets: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2017; 166:430-437. https://pubmed.ncbi.nlm.nih.gov/28135725

1210. SPRINT Research Group, Wright JT, Williamson JD et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015; 373:2103-16. https://pubmed.ncbi.nlm.nih.gov/26551272

1213. Reboussin DM, Allen NB, Griswold ME et al. Systematic review for the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018; 71:2176-2198. https://pubmed.ncbi.nlm.nih.gov/29146534

1214. American Diabetes Association. 9. Cardiovascular disease and risk management: standards of medical care in diabetes 2018. Diabetes Care. 2018; 41:S86-S104. https://pubmed.ncbi.nlm.nih.gov/29222380

1215. de Boer IH, Bangalore S, Benetos A et al. Diabetes and hypertension: a position statement by the American Diabetes Association. Diabetes Care. 2017; 40:1273-1284. https://pubmed.ncbi.nlm.nih.gov/28830958

1216. Taler SJ. Initial treatment of hypertension. N Engl J Med. 2018; 378:636-644. https://pubmed.ncbi.nlm.nih.gov/29443671

1217. Perkovic V, Rodgers A. Redefining Blood-Pressure Targets--SPRINT Starts the Marathon. N Engl J Med. 2015; 373:2175-8. https://pubmed.ncbi.nlm.nih.gov/26551394

1218. Messerli FH, Bangalore S, Bavishi C et al. Angiotensin-converting enzyme inhibitors in hypertension: to use or not to use?. J Am Coll Cardiol. 2018; 71:1474-1482. https://pubmed.ncbi.nlm.nih.gov/29598869

1219. Karmali KN, Lloyd-Jones DM. Global risk assessment to guide blood pressure management in cardiovascular disease prevention. Hypertension. 2017; 69:e2-e9. https://pubmed.ncbi.nlm.nih.gov/28115516

1220. Cifu AS, Davis AM. Prevention, detection, evaluation, and management of high blood pressure in adults. JAMA. 2017; 318:2132-2134. https://pubmed.ncbi.nlm.nih.gov/29159416

1222. Bell KJL, Doust J, Glasziou P. Incremental benefits and harms of the 2017 American College of Cardiology/American Heart Association high blood pressure guideline. JAMA Intern Med. 2018; 178:755-7. https://pubmed.ncbi.nlm.nih.gov/29710197

1223. LeFevre M. ACC/AHA hypertension guideline: what is new? what do we do?. Am Fam Physician. 2018; 97(6):372-3. https://pubmed.ncbi.nlm.nih.gov/29671534

1224. Brett AS. New hypertension guideline is released. From NEJM Journal Watch website. Accessed 2018 Jun 18. https://www.jwatch.org/na45778/2017/12/28/nejm-journal-watch-general-medicine-year-review-2017

1229. Ioannidis JPA. Diagnosis and treatment of hypertension in the 2017 ACC/AHA guidelines and in the real world. JAMA. 2018; 319(2):115-6. https://pubmed.ncbi.nlm.nih.gov/29242891

1230. Vasan RS, Larson MG, Leip EP et al. Impact of high-normal blood pressure on the risk of cardiovascular disease. N Engl J Med. 2001; 345(18):1291-7. https://pubmed.ncbi.nlm.nih.gov/11794147

1232. American Diabetes Association. 10. Microvascular complications and foot care: standards of medical care in diabetes 2018. Diabetes Care. 2018; 41:S86-S104. https://pubmed.ncbi.nlm.nih.gov/29222381

1235. Ogden LG, He J, Lydick E, Whelton PK. Long-term absolute benefit of lowering blood pressure in hypertensive patients according to the JNC VI risk stratification. Hypertension. 2000;35:539-543. https://pubmed.ncbi.nlm.nih.gov/10679494

1236. Leenen FHH, Nwachuku CE, Black HR et al. Clinical events in high-risk hypertensive patients randomly assigned to calcium-channel blocker versus angiotensin-converting enzyme inhibitor in the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial. Hypertension. 2006; 48:374-84. https://pubmed.ncbi.nlm.nih.gov/16864749

1237. Messerli FH, Staessen JA. Amlodipine better than lisinopril: how one randomized clinical trial ended fallacies from observational studies. Hypertension. 2006; 48:359-61. https://pubmed.ncbi.nlm.nih.gov/16894055

1238. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. Age-specific relevance of usual blood pressure to vascular mortality. Lancet. 2002;360:1903-13. https://pubmed.ncbi.nlm.nih.gov/12493255

b. Exner DV, Dries DL, Domanski MJ et al. Lesser response to angiotensin-converting-enzyme inhibitor therapy in black as compared with white patients with left ventricular dysfunction. N Engl J Med. 2001; 344:1351-7. https://pubmed.ncbi.nlm.nih.gov/11333991

d. BedfordLaboratories. Enalaprilat injection prescribing information. Bedford, OH; 2000 Sep.

e. Biovail. Vaseretic tablets (enalapril maleate and hydrochlorothiazide) prescribing information. Morrisville, NC; 2002 Aug.

HID. Trissel LA. Handbook on injectable drugs. 17th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2013:434-8.