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Guanfacine

Class: Central alpha-Agonists
VA Class: CV490
Chemical Name: N-Amidino-2-(2,6-dichlorophenyl) acetamide monohydrochloride
Molecular Formula: C9H9Cl2N3O
CAS Number: 29110-47-2

Medically reviewed by Drugs.com. Last updated on Mar 18, 2019.

Introduction

Phenylacetyl-guanidine derivative hypotensive agent; selective α2-adrenergic agonist.1 2

Uses for Guanfacine

Hypertension

Used alone or in combination with other classes of antihypertensive agents in the management of hypertension.1 3 4 5 1200

Not considered a preferred agent for initial management of hypertension according to current guidelines for the management of hypertension in adults, but may be used as add-on therapy if BP not adequately controlled with the recommended antihypertensive drug classes (i.e., ACE inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, thiazide diuretics).501 502 503 504 1200

Generally reserved as a last-line treatment option because of guanfacine's ability to cause substantial adverse CNS effects, especially in geriatric patients.1200

Has been used in conjunction with diuretics (e.g., thiazides), producing a greater reduction in BP than is obtained with either drug alone.1 5 16

Use of a diuretic or other antihypertensive agents may aid in overcoming tolerance to guanfacine and permit reduction of guanfacine dosage.2

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 patients501 504 compared with 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 2017 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 1229

For decisions regarding when to initiate drug therapy (BP threshold), the 2017 ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors.1200 1207 ASCVD risk assessment is 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 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 Consider initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes in adults with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.1200

Guanfacine 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.1200 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., ACE inhibitor, angiotensin II receptor antagonist, calcium-channel blocker, thiazide diuretic).1200 1216 Many patients will require ≥2 drugs from different pharmacologic classes to achieve BP goal; if goal BP still not achieved with 2 antihypertensive agents, add a third drug.1200 1216

Administration

Oral Administration

Minimize adverse effects (e.g., somnolence) by administering guanfacine initially at bedtime.1

Dosage

Available as guanfacine hydrochloride; dosage expressed in terms of guanfacine.1

Pediatric Patients

Hypertension
Oral

Children ≥12 years of age: Initially, 1 mg daily (as conventional tablets).1

If a satisfactory response is not obtained after 3–4 weeks of therapy, may increase dosage to 2 mg once daily at bedtime; however, most antihypertensive effect observed at dosage of 1 mg daily.1 5

Although higher dosages (i.e., >2 mg daily) have been used, dosages >3 mg daily (as conventional tablets) associated with a substantially increased incidence of adverse effects.1 2

Adults

Hypertension
Oral

Initially, 1 mg daily (as conventional tablets).1

If a satisfactory response is not obtained after 3–4 weeks of therapy, may increase dosage to 2 mg once daily at bedtime; however, most antihypertensive effect observed at dosage of 1 mg daily.1 5

Although higher dosages (i.e., >2 mg daily) have been used, dosages >3 mg daily (as conventional tablets) associated with substantially increased incidence of adverse effects.1 2

Some experts state usual dosage range is 0.5–2 mg once daily.1200

Prescribing Limits

Pediatric Patients

Hypertension
Oral

Children ≥12 years of age: Dosages >3 mg (as conventional tablets) daily were associated with a substantially increased incidence of adverse effects.1 2 5

Adults

Hypertension
Oral

Dosages >3 mg daily (as conventional tablets) were associated with a substantially increased incidence of adverse effects.1 2 5

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.1

Renal Impairment

Administer dosages at the low end of the dosing range in patients with renal impairment.1 16

May administer usual doses (possibly at low end of dosing range) in patients undergoing dialysis, because limited amounts of the drug are removed by dialysis.1

Geriatric Patients

Select dosage with caution (usually starting at the low end of the dosing range) because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.1

Cautions for Guanfacine

Contraindications

  • Known hypersensitivity to the drug.1

Warnings/Precautions

Sensitivity Reactions

Rash

Skin rash with exfoliation reported.1 Although causal relationship to guanfacine not established, discontinue drug if rash occurs and appropriately monitor patient.1

General Precautions

Withdrawal Effects

Risk of symptoms of nervousness and anxiety and, less commonly, rebound hypertension, if drug is stopped abruptly.1 Occurs less commonly than with clonidine;1 2 3 incidence may be about 3%.2

Following abrupt discontinuance of guanfacine, BP usually returns to pretreatment levels slowly (within 2–4 days) without ill effects.1 3 When rebound hypertension occurs, onset typically is 2–4 days after discontinuance of the drug (which is later than observed with clonidine hydrochloride).1

Cardiovascular Effects

Like other antihypertensive agents, use with caution in patients with severe coronary insufficiency, recent acute MI, or cerebrovascular disease.1

Nervous System Effects

Risk of dose-related sedation/drowsiness, especially during initial therapy.1 Performance of activities requiring mental alertness and physical coordination (operating machinery, driving a motor vehicle) may be impaired.1

Specific Populations

Pregnancy

Category B.1

Not recommended for the treatment of acute hypertension associated with toxemia of pregnancy.1

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 Use caution.1

Pediatric Use

Safety and efficacy for management of hypertension not established in children <12 years of age; use not recommended.1

Mania and aggressive behavioral changes reported in pediatric patients with attention deficit hyperactivity disorder (ADHD) receiving guanfacine (as conventional tablets);1 all patients had medical or family risk factors for bipolar disorder.1 All patients recovered following discontinuance of the drug.1

Geriatric Use

Clinical trial data for patients ≥65 years of age insufficient to determine whether geriatric patients respond differently than younger adults. 1 Other experience suggests that response is similar to that in younger adults.1

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.1

Hepatic Impairment

Like other antihypertensive agents, use guanfacine with caution in patients with chronic hepatic failure.1

Renal Impairment

Like other antihypertensive agents, use with caution in patients with chronic renal failure.1

Common Adverse Effects

Dry mouth,1 4 5 somnolence,1 3 4 5 dizziness,1 4 5 constipation,1 fatigue,1 4 5 asthenia,1 5 impotence,1 4 5 headache.1 4 5

Interactions for Guanfacine

Drugs Affecting Hepatic Microsomal Enzymes

In a limited number of patients with renal impairment, concomitant administration of guanfacine with a known microsomal enzyme inducer (phenobarbital or phenytoin) resulted in decreased elimination half-life and plasma concentrations of guanfacine.1 More frequent dosing of guanfacine may be required in patients receiving such concomitant therapy.1 (See Specific Drugs under Interactions.) Taper dosage of guanfacine when the drug is to be discontinued in patients receiving microsomal enzyme inducers; may avoid rebound hypertension or other symptoms.1

Specific Drugs

Drug

Interaction

Comments

Anticoagulants

Pharmacokinetic interaction unlikely1

Antigout drugs

Pharmacokinetic interaction unlikely1

Antilipemic agents

Pharmacokinetic interaction unlikely1

β-Adrenergic blocking agents

Pharmacokinetic interaction unlikely1

Bronchodilators

Pharmacokinetic interaction unlikely1

Cardiac drugs (glycosides, coronary vasodilators)

Pharmacokinetic interaction unlikely1

CNS depressants (barbiturates, benzodiazepines, phenothiazines)

May potentiate CNS depression1

Use concomitantly with caution1

Contraceptives, oral

Pharmacokinetic interaction unlikely1

Cough and cold preparations

Pharmacokinetic interaction unlikely1

Diuretics

Additive/potentiated hypotensive effect1

Pharmacokinetic interaction unlikely1

Usually used to therapeutic advantage in antihypertensive therapy1

Hypoglycemic agents (oral or insulin)

Pharmacokinetic interaction unlikely1

NSAIAs

Pharmacokinetic interaction unlikely1

Phenobarbital

Decreased elimination half-life and plasma concentration of guanfacine in patients with renal failure; 1 withdrawal reaction may occur1 2

In patients receiving phenobarbital, carefully taper guanfacine dosage when drug is to be discontinued1

Phenytoin

Decreased elimination half-life and plasma concentration of guanfacine in patients with renal failure; 1 withdrawal reaction may occur1

In patients receiving phenytoin, carefully taper guanfacine dosage when drug is to be discontinued 1

Guanfacine Pharmacokinetics

Absorption

Bioavailability

Absolute oral bioavailability (as conventional tablets) is about 80%.1 Peak plasma concentrations usually attained within 1–4 hours (average: 2.6 hours).1

Duration

BP response persists ≤24 hours following single oral dose (as conventional tablets).1

Distribution

Extent

Extensively distributed to tissues.1 2 Highest concentrations in highly perfused organs (e.g., kidney, liver); lower concentrations in the brain, testis, and plasma.2

Crosses the placenta in rats; not known whether crosses placenta in humans.1

Distributed into milk in rats; not known whether distributed into human milk.1

Plasma Protein Binding

Approximately 70%.1

Elimination

Metabolism

Approximately 50–70% of a dose (as conventional tablets) is metabolized rapidly in the liver,1 2 mainly by oxidative metabolism of the aromatic ring to form the inactive 3-hydroxy derivative (major metabolite),1 2 which undergoes conjugation.2

Elimination Route

It appears that the drug is excreted by tubular secretion.1

In patients with normal renal function, guanfacine (as conventional tablets) eliminated principally in the urine as unchanged drug (about 50%; range: 40–75%),1 with remainder eliminated mostly as glucuronide (30–40%) or sulfate (8%).2

Half-life

In patients with normal renal function (guanfacine conventional tablets): about 17 hours (range: 10–30 hours).1 2

Special Populations

Clearance reduced in patients with renal impairment; however, plasma concentrations of drug only slightly increased.1

Within the reported range of elimination half-lives (10–30 hours), elimination half-life of guanfacine (conventional tablets) tends to be shorter (13–14 hours) in younger patients and longer (in the upper end of the range) in older patients.1

Stability

Storage

Oral

Conventional Tablets

Tight, light-resistant containers at 15–30°C.1

Actions

  • Appears to stimulate α2-adrenergic receptors in the CNS, causing inhibition of sympathetic vasomotor centers.1 2 Contributes predominantly to hypotensive effects.1 2

  • Central effects result in reduced peripheral sympathetic nerve impulses from the vasomotor center to the heart and blood vessels, resulting in a decrease in peripheral vascular resistance and a reduction in heart rate.1

  • Under conditions of rest or exercise, cardiac output is not altered.1

  • Reduces BP in both supine and standing positions;1 hypotensive effects may be somewhat greater in the standing position.2

  • Peripheral effects (stimulation of peripheral α2-adrenergic receptors) also may contribute to hypotensive effects.2

  • Lowers elevated plasma renin activity and plasma catecholamine concentrations in patients with hypertension, although these effects do not correlate with individual hypotensive responses.1 2

  • Acute administration stimulates release of growth hormone, but the drug does not produce sustained elevation of growth hormone during chronic administration.1 2

  • Does not affect plasma aldosterone, mean body weight, or electrolytes; slight but insignificant increase in plasma volume observed after 1 month of therapy.1

  • Reduces serum prolactin concentrations in hypertensive patients with elevated serum prolactin concentrations.2

  • Enhances neurologic activity in the prefrontal cortex, an area of the brain involved in planning, impulse control, and organization.10 Shown in nonhuman primates to improve prefrontal cortical function through direct action on postsynaptic α2A-adrenergic receptors located in the prefrontal cortex.9

  • Sedative effects, which are less severe than those seen with clonidine,3 9 are the result of inhibitory effects on noradrenergic locus ceruleus neurons and direct effects on the thalamus.9

Advice to Patients

  • Importance of advising patients not to discontinue therapy abruptly because of the risk of withdrawal symptoms (e.g., nervousness, anxiety) and, less commonly, rebound hypertension.1 (See Withdrawal Effects under Cautions.)

  • Importance of advising patients to exercise caution when operating dangerous machinery or driving motor vehicles until it is known that the drug is not causing untoward dizziness or drowsiness.1

  • Importance of advising patients of the potential for decreased tolerance for alcohol and other CNS depressants.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing 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

guanFACINE Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

1 mg (of guanfacine)*

Guanfacine Hydrochloride Tablets

2 mg (of guanfacine)*

Guanfacine Hydrochloride Tablets

AHFS DI Essentials™. © Copyright 2019, Selected Revisions March 18, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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

References

1. Watson Laboratories, Inc. Guanfacine hydrochloride tablets prescribing information. Corona, CA; 2003 Apr.

2. Cornish LA. Guanfacine hydrochloride: a centrally acting antihypertensive agent. Clin Pharm. 1988; 7:187-97. http://www.ncbi.nlm.nih.gov/pubmed/3281788?dopt=AbstractPlus

3. Wilson MF, Haring G, Lewin A et al. Comparison of guanfacine versus clonidine for efficacy, safety, and occurrence of withdrawal syndrome in step-2 treatment of mild to moderate essential hypertension. Am J Cardiol. 1986; 57:E43-49.

4. Wilson MF, Blackshear J, Parsons OA et al. Antihypertensive efficacy of guanfacine and methyldopa in patients with mild to moderate essential hypertension. J Clin Pharmacol. 1991; 31:318-26. http://www.ncbi.nlm.nih.gov/pubmed/2037703?dopt=AbstractPlus

5. Materson BJ, Kessler WB, Alderman MH et al. A multicenter, randomized, double-blind dose-response evaluation of step-2 guanfacine versus placebo in mild to moderate hypertension. Am J Cardiol. 1986; 57:E32-37.

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

9. Scahill L, Chappell PB, Kim YS et al. A placebo-controlled study of guanfacine in the treatment of children with tic disorders and attention deficit hyperactivity disorder. Am J Psychiatry. 2001; 158:1067-74. http://www.ncbi.nlm.nih.gov/pubmed/11431228?dopt=AbstractPlus

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16. Reviewers' comments (personal observations.)

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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. http://www.ncbi.nlm.nih.gov/pubmed/23817082?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/24243703?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/24341872?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/24424788?dopt=AbstractPlus

506. Mitka M. Groups spar over new hypertension guidelines. JAMA. 2014; 311:663-4. http://www.ncbi.nlm.nih.gov/pubmed/24549531?dopt=AbstractPlus

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

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

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

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.

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; :. http://www.ncbi.nlm.nih.gov/pubmed/24788967?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/24641124?dopt=AbstractPlus

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.

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. J Am Coll Cardiol. 2017; http://www.ncbi.nlm.nih.gov/pubmed/29146535?dopt=AbstractPlus

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

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. http://www.ncbi.nlm.nih.gov/pubmed/29357392?dopt=AbstractPlus

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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. http://www.ncbi.nlm.nih.gov/pubmed/28135725?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/26551272?dopt=AbstractPlus

1216. Taler SJ. Initial treatment of hypertension. N Engl J Med. 2018; 378:636-644. http://www.ncbi.nlm.nih.gov/pubmed/29443671?dopt=AbstractPlus

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

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. http://www.ncbi.nlm.nih.gov/pubmed/29710197?dopt=AbstractPlus

1223. LeFevre M. ACC/AHA hypertension guideline: what is new? what do we do?. Am Fam Physician. 2018; 97(6):372-3. http://www.ncbi.nlm.nih.gov/pubmed/29671534%20?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/29242891?dopt=AbstractPlus

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