Questions about Atrial Fibrillation? Get answers from our expert.

Generic Name: Ramipril
Class: Angiotensin-Converting Enzyme Inhibitors
VA Class: CV800
Chemical Name: [2S - [1[R*(R*)],2α,3aβ,6aβ]] - 1 - [2 - [[1 - (Ethoxycarbonyl) - 3 - phenylpropyl]amino] - 1 - oxopropy l]octahydrocylopenta[b]pyrrole-2-carboxylic acid
Molecular Formula: C21H28N2O5
CAS Number: 87333-19-5

Warning(s)

  • May cause fetal and neonatal morbidity and mortality if used during pregnancy.1 39 40 41 42 43 44 45 46 88 89 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • If pregnancy is detected, discontinue ramipril as soon as possible.1 89

Introduction

Nonsulfhydryl ACE inhibitor.1 2 3

Uses for Altace

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).1 2 4 500

ACE inhibitors are recommended as one of several preferred agents for the initial management of hypertension; other options include angiotensin II receptor antagonists, calcium-channel blockers, and thiazide diuretics.501 502 503 504 While there may be individual differences with respect to specific outcomes, these antihypertensive drug classes all produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.500 501 502 504 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).500 501 502 503 504 515

ACE inhibitors may be preferred in hypertensive patients with heart failure, ischemic heart disease, diabetes mellitus, chronic kidney disease, or cerebrovascular disease or post-MI.500 501 502 504 520 523 524 525 526 527 534 535 536 543

Slideshow: Seasoned Pro: Be Mindful of These Winter Health Hazards

Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to ACE inhibitors.14 67 68 86 87 500 501 504 However, diminished response to an ACE inhibitor is largely eliminated when administered concomitantly with a calcium-channel blocker or thiazide diuretic.14 16 17 500 504

The optimum BP threshold for initiating antihypertensive drug therapy is controversial.501 504 505 506 507 508 515 523 530 Further study needed to determine optimum BP thresholds/goals; individualize treatment decisions.501 503 507 515 526 530

JNC 7 recommends initiation of drug therapy in all patients with uncomplicated hypertension and BP ≥140/90 mm Hg;500 JNC 8 panel recommends SBP threshold of 150 mm Hg for patients ≥60 years of age.501 Although many experts agree that SBP goal of <150 mm Hg may be appropriate for patients ≥80 years of age,502 504 505 530 application of this goal to those ≥60 years of age is controversial, especially for those at higher cardiovascular risk.501 502 505 506 508 511 515

In the past, initial antihypertensive drug therapy was recommended for patients with diabetes mellitus or chronic kidney disease who had BP ≥130/80 mm Hg;500 503 current hypertension management guidelines generally recommend a BP threshold of 140/90 mm Hg for these individuals (same as for the general population of patients without these conditions), although a goal of <130/80 mm Hg may still be considered.501 502 503 504 520 530 535 536 541

Heart Failure after MI

Reduction of the risk of mortality in hemodynamically stable patients who have demonstrated clinical signs of congestive heart failure within a few days following acute MI.1 2 12 18 21 24 27 28 62 Also may reduce rate of heart failure-associated hospitalization and progression to severe and/or resistant heart failure.1 2 12 18 21 24 27 28 62

Prevention of Cardiovascular Events

Reduction of the risk of cardiovascular death, MI, and stroke in patients ≥55 years of age who are at high risk for cardiovascular events (e.g., those with a history of CAD, stroke, peripheral vascular disease, or diabetes mellitus in addition to ≥1 other cardiovascular risk factor [e.g., hypertension, elevated total cholesterol and/or decreased HDL-cholesterol concentrations, smoking, documented microalbuminuria]) but who are not known to have low ventricular ejection fraction or heart failure.1 47 48

Reduction in the incidence of diabetic complications and in new diagnosis of diabetes also reported.47 48

Heart Failure

Management of heart failure, usually in conjunction with cardiac glycosides, diuretics, and β-blockers.62 70 71 72 73 74

Diabetic Nephropathy

A recommended agent in the management of patients with diabetes mellitus and persistent albuminuria 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.81 82 83 84 85 520 535 536

Altace Dosage and Administration

General

BP Monitoring and Treatment Goals

  • Carefully monitor BP during initial titration or subsequent upward adjustment in dosage.500 501

  • When available, use evidence-based dosing information (i.e., dosages shown in randomized controlled trials to reduce complications of hypertension) to determine target dosages; target dosages usually can be achieved within 2–4 weeks but may take up to several months.501

  • If adequate BP response not achieved with a single antihypertensive agent, add a second drug with demonstrated benefit; if goal BP still not achieved with optimal dosages of 2 antihypertensive agents, add a third drug.501 May maximize dosage of the first drug before adding a second drug, or add a second drug before maximizing dosage of the initial drug.501

  • Consider initiating antihypertensive therapy with a combination of drugs if patient's BP exceeds goal BP by >20/10 mm Hg.500 501 503 504

  • Goal is to achieve and maintain optimal control of BP; individualize specific target BP based on consideration of multiple factors, including patient age and comorbidities, and currently available evidence from clinical studies.500 501 (See Hypertension under Uses.)

Administration

Oral Administration

Administer orally once or twice daily.1

Swallow capsules whole.1 Alternatively, open capsules and sprinkle contents on small amount (about 120 mL) of applesauce or mix in 120 mL of water or apple juice.1 Consume entire mixture to ensure that no drug is lost.1 (See Storage under Stability.)

Dosage

In patients currently receiving diuretic therapy, discontinue diuretic, reduce diuretic dosage, or increase salt intake prior to initiating ramipril.600 If such changes are not possible, initiate ramipril in adults at a reduced dosage of 1.25 mg once daily.600 (See Hypotension under Cautions and see the individual dosage sections in Dosage and Administration.)

Adults

Hypertension
Oral

Initially, 2.5 mg once daily in patients not receiving diuretic therapy.600 In patients receiving a diuretic, initiate ramipril at 1.25 mg once daily.600 Adjust subsequent dosage based on BP response.600

Usual maintenance dosage: 2.5–20 mg daily, given in 1 dose or 2 divided doses.500 600

If effectiveness diminishes toward end of dosing interval in patients treated once daily, consider increasing dosage or administering drug in 2 divided doses.600

If intolerable adverse effects occur, consider dosage reduction; if adverse effects worsen or fail to resolve, may need to discontinue and switch to another antihypertensive drug class.501

Heart Failure after MI
Oral

Initially, 2.5 mg twice daily, beginning as early as 2 days after MI.1 12 If hypotension occurs, reduce dosage to 1.25 mg twice daily.1 After 1 week at initial dosage, adjust dosage as tolerated at 3-week intervals to target dosage of 5 mg twice daily.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.1

Prevention of Cardiovascular Events
Oral

Initially, 2.5 mg once daily for 1 week, followed by 5 mg once daily for 3 weeks; subsequently increase dosage as tolerated to maintenance dosage of 10 mg once daily.1 In patients with hypertension or those with recent MI, may administer total daily dosage in divided doses.1

Special Populations

Renal Impairment

Initial dosage of 1.25 mg once daily recommended in patients with renal artery stenosis.1

In patients with Clcr <40 mL/minute, 25% of the usual doses are expected to induce full therapeutic concentrations of ramiprilat.1

Hypertension
Oral

Initially, 1.25 mg once daily in patients with Clcr <40 mL/minute.1 Titrate until BP is controlled or to maximum dosage of 5 mg daily.1

Heart Failure after MI
Oral

Initially, 1.25 mg once daily in patients with Clcr <40 mL/minute.1 May increase dosage to 1.25 mg twice daily; subsequently titrate according to clinical response and tolerance up to maximum dosage of 2.5 mg twice daily.1

Volume-and/or Salt-Depleted Patients

Correct volume and/or salt depletion prior to initiation of therapy or initiate therapy at dosage of 1.25 mg once daily.1

Cautions for Altace

Contraindications

  • Known hypersensitivity (e.g., history of angioedema) to ramipril or another ACE inhibitor.1

Warnings/Precautions

Warnings

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

Hypotension

Possible symptomatic hypotension, particularly in volume- and/or salt-depleted patients (e.g., those receiving prolonged diuretic therapy or undergoing dialysis, those with dietary salt restriction, patients with diarrhea or vomiting).1 Risk of excessive hypotension, sometimes associated with oliguria, azotemia, and, rarely, acute renal failure and death in patients with heart failure with or without associated renal insufficiency.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 circumstances.1 Correct volume and/or salt depletion (e.g., by withholding diuretic therapy, reducing diuretic dosage, increasing sodium intake) prior to initiation of ramipril or reduce initial dosage.1 600 (See Dosage and also Special Populations, under Dosage and Administration.)

In patients at risk of excessive hypotension, initiate therapy under close medical supervision; monitor closely for first 2 weeks following initiation of ramipril or any increase in ramipril or diuretic dosage.1

If hypotension occurs, place patient in supine position and, if necessary, administer IV infusion of physiological saline.1 Ramipril therapy usually can be continued following restoration of volume and BP.1

Hematologic Effects

Neutropenia and agranulocytosis reported with captopril; risk appears to depend principally on presence of renal impairment and/or presence of collagen vascular disease (e.g., systemic lupus erythematosus, scleroderma);1 also reported in patients receiving immunosuppressive therapy.5 6 Hematologic effects (e.g., agranulocytosis; pancytopenia; bone marrow depression; reductions in hemoglobin content or leukocyte, erythrocyte, or platelet counts) reported rarely with ramipril.1

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 used during pregnancy.1 88 89 (See Boxed Warning.) Such potential risks occur throughout pregnancy, especially during the second and third trimesters.89

Also may increase the risk of major congenital malformations when administered during the first trimester of pregnancy.88 89

Discontinue as soon as possible when pregnancy is detected, unless continued use is considered lifesaving.89 Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy.44 46

Sensitivity Reactions

Anaphylactoid reactions and/or head and neck angioedema possible; if associated with laryngeal edema, may be fatal.1 Immediate medical intervention (e.g., epinephrine) for involvement of tongue, glottis, or larynx.1

Intestinal angioedema possible; consider in differential diagnosis of patients who develop abdominal pain.1

Anaphylactoid reactions reported in patients receiving ACE inhibitors while undergoing LDL apheresis with dextran sulfate absorption or following initiation of hemodialysis that utilized high-flux membrane.1

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

Contraindicated in patients with a history of angioedema associated with ACE inhibitors.1 47 Patients with history of angioedema unrelated to ACE inhibitors may be at increased risk of angioedema associated with ACE inhibitor therapy.1

General Precautions

Renal Effects

Transient increases in BUN and Scr possible, especially in patients with preexisting renal impairment or those receiving concomitant diuretic therapy.1 Possible increases in BUN and Scr in patients with unilateral or bilateral renal artery stenosis; generally reversible following discontinuance of ramipril and/or diuretic therapy.1

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

Closely monitor renal function for the first few weeks of therapy in hypertensive patients with unilateral or bilateral renal-artery stenosis.1 Some patients may require dosage reduction or discontinuance of ACE inhibitor or diuretic therapy.1

Hyperkalemia

Possible hyperkalemia, especially in patients with renal impairment or diabetes mellitus and those receiving drugs that can increase serum potassium concentration (e.g., potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes).1 (See Interactions.)

Cough

Persistent and nonproductive cough; resolves after drug discontinuance.1

Specific Populations

Pregnancy

Category C (1st trimester); Category D (2nd and 3rd trimesters).1 (See Fetal/Neonatal Morbidity and Mortality under Cautions and see Boxed Warning.)

Lactation

Undetectable in human milk following single oral dose; not known whether distributed into milk following multiple doses.1 Use not recommended.1

Pediatric Use

Safety and efficacy not established in children <18 years of age.1

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.1

Hepatic Impairment

Use with caution in patients with cirrhosis and/or ascites, due to possible increased activity of renin-angiotensin-aldosterone system.1

Possible marked increase in plasma ramipril concentrations; peak plasma ramiprilat concentrations not appreciably altered. (See Absorption: Special Populations, under Pharmacokinetics.)1

Renal Impairment

Systemic exposure to ramiprilat may be increased.1 (See Pharmacokinetics.) Initial dosage adjustment may be necessary depending on degree of renal impairment.1 (See Renal Impairment under Dosage and Administration.)

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

Black Patients

BP reduction may be smaller in black patients compared with nonblack patients.1 14 15 67 68 (See Hypertension under Uses.)

Higher incidence of angioedema reported with ACE inhibitors in black patients compared with other races.1 68 500

Common Adverse Effects

Patients with hypertension: Headache, dizziness, fatigue.1

Patients with heart failure: Dizziness, cough, nausea, vomiting, angina pectoris, syncope, postural hypotension, vertigo, hypotension.1

Interactions for Altace

Specific Drugs

Drug

Interaction

Comments

Antacid

Pharmacokinetic interaction unlikely1

Antidiabetic agents (insulin, oral agents)

Possible hypoglycemia in diabetic patients1

Monitor closely for symptoms of hypoglycemia following initiation or dosage adjustment of ramipril; adjust dosage of antidiabetic agent as necessary1

Cimetidine

Pharmacokinetic interaction unlikely1

Digoxin

Pharmacokinetic interaction unlikely1

Diuretics

Increased hypotensive effect1

If possible, discontinue or decrease dosage of diuretic before initiating ramipril600 (see Dosage and also Special Populations, under Dosage and Administration)

Diuretics, potassium-sparing (amiloride, spironolactone, triamterene)

Enhanced hyperkalemic effect1

Use with caution; monitor serum potassium concentrations frequently1

Lithium

Increased serum lithium concentrations; possible toxicity1

Use with caution; monitor serum lithium concentrations frequently1

NSAIAs

Potential for reduction of renal function and increase in serum potassium1

No interaction observed with indomethacin1

Potassium supplements or potassium-containing salt substitutes

Enhanced hyperkalemic effect1

Use with caution; monitor serum potassium concentrations frequently1

Simvastatin

Pharmacokinetic interaction unlikely1

Warfarin

Pharmacologic interaction unlikely1

Altace Pharmacokinetics

Absorption

Bioavailability

Following oral administration, peak plasma concentrations of ramipril usually attained within 1 hour.1 Peak plasma concentrations of ramiprilat attained within 2–4 hours after oral dose.1 About ≥50–60% of an oral dose is absorbed.1

Onset

Following multiple oral doses (≥2 mg), >90% inhibition of plasma ACE activity achieved 4 hours after dosing.1

Duration

Following multiple oral doses (≥2 mg), inhibition of >80% of plasma ACE activity persists for about 24 hours.1

Food

Food decreases rate but not extent of absorption.1 Opening the capsules and sprinkling the contents on applesauce or mixing the contents in apple juice does not alter serum concentrations of ramiprilat.1 (See Oral Administration under Dosage and Administration.)

Special Populations

In patients with hepatic impairment, plasma concentrations of ramipril are increased; peak plasma ramiprilat concentrations are similar to those in individuals with normal hepatic function.1

In patients with renal impairment (Clcr <40 mL/minute per 1.73m2), plasma concentrations and AUC of ramiprilat are increased, and time to peak plasma ramiprilat concentrations is slightly prolonged.1

Distribution

Extent

Distributes into a large peripheral compartment.1 Crosses the placenta.1 Undetectable in human milk following single oral dose; not known whether distributed into milk following multiple doses.1

Plasma Protein Binding

Ramipril: About 73%.1

Ramiprilat: About 56%.1

Elimination

Metabolism

Metabolized mainly in the liver, principally to an active metabolite, ramiprilat.1

Elimination Route

Excreted in urine (60%) as unchanged drug and ramiprilat and in feces (approximately 40%).1

Half-life

Triphasic; apparent elimination half-life of ramiprilat: Approximately 13–17 hours.1

Special Populations

In patients with Clcr <40 mL/minute per 1.73m2, urinary excretion of ramipril, ramiprilat, and their metabolites is decreased.1

Stability

Storage

Oral

Capsules

15–30 ºC.1

Mixtures of ramipril with applesauce, water, or apple juice (see Oral Administration under Dosage and Administration) are stable for 24 hours at room temperature and 48 hours when refrigerated.1

Actions

  • Prodrug; has little pharmacologic activity until metabolized to ramiprilat.1

  • Suppresses the renin-angiotensin-aldosterone system.1

Advice to Patients

  • Risk of angioedema, anaphylactoid reactions, or other sensitivity reactions.1 47 Importance of reporting sensitivity reactions (e.g., edema of face, eyes, lips, tongue, larynx, 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 88 89 (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 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.

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

Ramipril

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

1.25 mg*

Altace

Pfizer

Ramipril Capsules

2.5 mg*

Altace

Pfizer

Ramipril Capsules

5 mg*

Altace

Pfizer

Ramipril Capsules

10 mg*

Altace

Pfizer

Ramipril Capsules

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2015. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Altace 1.25MG Capsules (MONARCH PHARMACEUTICALS): 30/$67.99 or 90/$185.97

Altace 10MG Capsules (MONARCH PHARMACEUTICALS): 30/$90.99 or 90/$250.96

Altace 2.5MG Capsules (MONARCH PHARMACEUTICALS): 30/$77.99 or 90/$213.98

Altace 5MG Capsules (MONARCH PHARMACEUTICALS): 30/$81.99 or 90/$217.98

Ramipril 1.25MG Capsules (LUPIN PHARMACEUTICALS): 100/$99.99 or 300/$275.97

Ramipril 10MG Capsules (WATSON LABS): 30/$62.99 or 90/$179.97

Ramipril 2.5MG Capsules (WATSON LABS): 30/$49.99 or 90/$139.97

Ramipril 5MG Capsules (WATSON LABS): 30/$52.99 or 90/$149.99

AHFS DI Essentials. © Copyright, 2004-2015, Selected Revisions January 6, 2015. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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

References

1. Monarch. Altace (ramipril) capsules prescribing information. Kansas City, MO; 2005 Sep.

2. Frampton JE, Peters DH. Ramipril: an updated review of its therapeutic use in essential hypertension and heart failure. Drugs. 1995;49:440-466.

3. Anon. Three new ACE inhibitors for hypertension. Med Lett Drugs Ther. 1991; 33:83-4. [PubMed 1831531]

4. McAreavey D, Robertson JI. Angiotensin converting enzyme inhibitors and moderate hypertension. Drugs. 1990; 40:326-45. [PubMed 2226219]

5. Squibb. Capoten (captopril) tablets prescribing information. In: Physician’s desk reference. 47th ed. Montvale, NJ: Medical Economics Company Inc; 1993:2356-62.

6. Reviewers’ comments on Enalaprilat/Enalapril 24:32.04 (personal observations).

8. Anon. Drugs for hypertension. Med Lett Drugs Ther. 1984; 26:107-12. [PubMed 6150424]

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

12. 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. [IDIS 320478] [PubMed 8104270]

14. Saunders E. Tailoring treatment to minority patients. Am J Med. 1990; 88(Suppl 3B):21-23S. [PubMed 2294761]

15. Chrysant SG, Danisa K, Kem DC et al. Racial differances in pressure, volume and renin interrelationships in essential hypertension. Hypertension. 1979; 1:136-41. [PubMed 399939]

16. Holland OB, Kuhnert L, Campbell WB et al. Synergistic effect of captopril with hydrochlorothiazide for the treatment of low-renin hypertensive black patients. Hypertension. 1983; 5:235-9. [PubMed 6337951]

17. Ferguson RK, Vlasses PH, Rotmesch HH. Clinical applications of angiotensin-enzyme inhibitors. Am J Med. 1984; 77:690-8. [IDIS 191617] [PubMed 6091446]

18. LeJemtel TH, Hochman JS, Sonnenblick EH. Indications for immedicate angiotensin-converting enzyme inhibition in patients with acute myocardial infarction. J Am Coll Cardiol. 1995; 25(Suppl):47-51S. [PubMed 7798525]

19. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico. GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate single and together on 6-week mortality and ventricular function after acute myocardial infarction. Lancet. 1994; 343:1115-22. [IDIS 329049] [PubMed 7910229]

20. 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. [IDIS 340649] [PubMed 7990904]

21. 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.

22. 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.

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

24. Anon. An ACE inhibitor after a myocardial infarction. Med Lett Drugs Ther. 1994; 36:69-70. [PubMed 8035753]

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

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

27. 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)

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

29. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. ISIS-4: a randomised factorial trial assesssing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58 050 patients with suspected acute myocardial infarction. Lancet. 1995; 345:669-85. [PubMed 7661937]

30. 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. [IDIS 344925] [PubMed 7885123]

31. Cohn JN. The prevention of heart failure—a new agenda. N Engl J Med. 1992; 327:725-7. [IDIS 301135] [PubMed 1495526]

32. Pfeffer MA, Braunwald E, Moyé LA et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 1992; 327:669-77. [IDIS 301129] [PubMed 1386652]

33. 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. [IDIS 301130] [PubMed 1495520]

34. 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. [IDIS 279768] [PubMed 1672967]

35. 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. [IDIS 288996] [PubMed 1892076]

36. Sharpe N, Murphy J, Smith H et al. Treatment of patients with symptomless left ventricular dysfunction after myocardial infarction. Lancet. 1988; 1:255-9. [IDIS 238337] [PubMed 2893080]

37. 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. [IDIS 243316] [PubMed 2967917]

38. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Bethesda, MD: National Institutes of Health; 1997 Nov. (NIH publication No. 98-4080.)

39. Rey E, LeLorier J, Burgess E et al. Report of the Canadian Hypertension Society consensus conference: 3. pharmacologic treatment of hypertensive disorders in pregnancy. CMAJ. 1997; 157:1245-54. [IDIS 396283] [PubMed 9361646]

40. American College of Obstetricians and Gynecologists. ACOG technical bulletin No. 219: hypertension in pregnancy. 1996 Jan.

41. Hanssens M, Keirse MJ, Van Assche FA. Fetal and neonatal effects of treatment with angiotensin-converting enzyme inhibitors in pregnancy. Obstet Gynecol. 1991; 78:128-35. [IDIS 284531] [PubMed 2047053]

42. Brent RL, Beckman D. Angiotensin-converting enzyme inhibitors, an embryopathic class of drugs with unique properties: information for clinical teratology counselors. Teratology. 1991; 43:543-6. [PubMed 1882342]

43. Piper JM, Ray WA, Rosa FW. Pregnancy outcome following exposure to angiotensin-converting enzyme inhibitors. Obstet Gynecol. 1992; 80:429-32. [IDIS 300973] [PubMed 1495700]

44. Sibai BM. Treatment of hypertension in pregnant women. N Engl J Med. 1996; 335:257-65. [IDIS 369138] [PubMed 8657243]

45. Barr M, Cohen MM. ACE inhibitor fetopathy and hypocalvaria: the kidney-skull connection. Teratology. 1991; 44:485-95. [PubMed 1771591]

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

47. Yusuf S, Sleight P, Pogue J et al for the Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on death from cardiovascular causes, myocardial infarction, and stroke in high-risk patients. N Engl J Med. (in press)

48. Kleinert S. HOPE cardiovascular disease prevention with ACE inhibitor ramipril. Lancet. 1999; 354:841. [PubMed 10485736]

49. Hansson L, Lindholm LH, Niskanen L et al. Effects of angiotensin-converting enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial. Lancet. 1999; 353:611-616. [IDIS 421531] [PubMed 10030325]

50. Lonn EM, Yusuf S, Jha P et al. Emerging role of angiotensin-converting enzyme inhibitors in cardiac and vascular protection. Circulation. 1994; 90:2056-69. [IDIS 336978] [PubMed 7923694]

52. Genuth S. United Kingdom prospective diabetes study results are in. J Farm Pract. 1998; 47(Suppl 5):S27.

53. Watkins PJ. UKPDS: a message of hope and a need for change. Diabetic Med. 1998; 15:895-6. [PubMed 9827842]

54. UK Prospective Diatetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998; 317:703-13. [IDIS 412064] [PubMed 9732337]

55. 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. [PubMed 9831300]

57. 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. [IDIS 403787] [PubMed 9571349]

58. 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.

59. UK Prospective Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. BMJ. 1998; 317:713-20. [IDIS 412065] [PubMed 9732338]

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

62. 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; 83:9-38A.

63. Izzo JL, Levy D, Black HR. Importance of systolic blood pressure in older Americans. Hypertension. 2000; 35:1021-4. [PubMed 10818056]

64. Frohlich ED. Recognition of systolic hypertension for hypertension. Hypertension. 2000; 35:1019-20. [PubMed 10818055]

65. 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. [IDIS 452007] [PubMed 10977801]

66. Associated Press (American Diabetes Association). Diabetics urged: drop blood pressure. Chicago, IL; 2000 Aug 29. Press Release from web site.

67. Appel LJ. The verdict from ALLHAT—thiazide diuretics are the preferred initial therapy for hypertension. JAMA. 2002; 288:3039-60. [IDIS 490723] [PubMed 12479770]

68. 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. [IDIS 490721] [PubMed 12479763]

70. Merck & Co. Vasotec tablets (enalapril maleate) prescribing information. Whitehouse Station, NJ; 2002 Jan.

71. Bristol-Myers Squibb. Monopril (fosinopril sodium) tablets prescribing information. Princeton, NJ; 2002 Feb.

72. Merck. Prinivil (lisinopril) tablets prescribing information. Whitehouse Station, NJ; 2002 Jan.

73. AstraZeneca. Zestril (lisinopril) tablets prescribing information. Wilmington, DE: 2002 Jan.

74. Parke Davis. Accupril (quinapril hydrochloride) tablets prescribing information. Morris Plains, NJ; 2001 Mar.

77. Novartis. Diovan (valsartan) tablets prescribing information. East Hanover, NJ; 2002 Aug.

81. Lewis EJ, Hunsicker LG, Bain RP et al. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med. 1993; 329:1456-62. [IDIS 321612] [PubMed 8413456]

82. Remuzzi G. Slowing the progression of diabetic nephropathy. N Engl J Med. 1993; 329:1496-7. [PubMed 8413463]

83. Kaplan NM. Choice of initial therapy for hypertension. JAMA. 1996; 275:1577-80. [IDIS 365188] [PubMed 8622249]

84. Viberti G, Mogensen CE, Groop LC et al. Effect of captopril on progression to clinical proteinuria in patients with insulin-dependent diabetes mellitus and microalbuminuria. JAMA. 1994; 271:275-9. [IDIS 324307] [PubMed 8295285]

85. Fournier A. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med. 1994; 330:937. [PubMed 8114873]

86. 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. [IDIS 531054] [PubMed 15811979]

87. Neaton JD, Kuller LH. Diuretics are color blind. JAMA. 2005; 293:1663-6. Editorial. [IDIS 531056] [PubMed 15811986]

88. 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. [PubMed 16760444]

89. Food and Drug Administration. FDA public health advisory: angiotensin-converting enzyme inhibitor (ACE inhibitor) drugs and pregnancy. From FDA website.

90. Bristol-Myers Squibb Co. Capoten tablets (captopril tablets) prescribing information. In: Physicians’ desk reference. 49th ed. Montvale, NJ: Medical Economics Company Inc; 1995:710-4.

91. Bristol-Myers Squibb. Monopril (fosinopril sodium) tablets prescribing information. Princeton, NJ; 2002 Feb.

92. Parke Davis. Accupril (quinapril hydrochloride) tablets prescribing information. Morris Plains, NJ; 2001 Mar.

93. Merck. Prinivil (lisinopril) tablets prescribing information. Whitehouse Station, NJ; 2002 Jan.

94. Merck & Co. Vasotec tablets (enalapril maleate) prescribing information. Whitehouse Station, NJ; 2002 Jan.

95. Ciba Pharmaceutical Company. Lotensin (benazepril hydrochloride) tablets prescribing information. In: Physicians’ desk reference. 49th ed. Montvale, NJ: Medical Economics Company Inc; 1995:887-90.

96. Schwarz Pharma. Univasc™ (moexipril hydrochloride) tablets prescribing information. Milwaukee, WI; 2003 May.

97. Cobalt Pharmaceuticals, Bristol, TN: Personal communication.

500. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC I). Bethesda, MD: National Institutes of Health; 2003 Aug. (NIH publication No. 04-5230.)

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. [PubMed 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. [PubMed 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. [PubMed 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. [PubMed 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. [PubMed 24424788]

506. Mitka M. Groups spar over new hypertension guidelines. JAMA. 2014; 311:663-4. [PubMed 24549531]

507. Peterson ED, Gaziano JM, Greenland P. Recommendations for treating hypertension: what are the right goals and purposes?. JAMA. 2014; 311:474-6. [PubMed 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. [PubMed 24352759]

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. [PubMed 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. [PubMed 24591473]

520. American Diabetes Association. Standards of medical care in diabetes--2014. Diabetes Care. 2014; 37 Suppl 1:S14-80. [PubMed 24357209]

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. [PubMed 23166211]

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. [PubMed 23741058]

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. [PubMed 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; :. [PubMed 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. [PubMed 23247304]

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. [PubMed 24641124]

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. [PubMed 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. [PubMed 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.

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. [PubMed 22555213]

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.

600. Pfizer. Altace (ramipril) capsules prescribing information. NY, NY; 2013 May.

Hide
(web4)