By Wilbert S. Aronow, MD, FACC and Julio A. Panza, MD, FACC*
Although lifestyle measures are an essential part of the treatment of hypertension, antihypertensive drugs are required in the vast majority of patients in order to achieve their blood pressure goals.1-4 This article reviews the most current recommendations for pharmacotherapy in essential hypertension, with a focus on the suggested drugs for the most common associated conditions.
According to the most recent guideline, patients with clinical cardiovascular disease (coronary heart disease, heart failure, and stroke) should have their blood pressure reduced to less than 130/80 mm Hg for secondary prevention of recurrent events.4 Similarly, blood pressure should be lowered below 130/80 mm Hg for primary prevention of cardiovascular disease in persons with an estimated 10-year risk of atherosclerotic cardiovascular disease ≥10%.4,5 In contrast, blood pressure should be lowered below 140/90 mm Hg for primary prevention when the estimated 10-year risk of atherosclerotic cardiovascular disease is <10%.4,5 Antihypertensive drug therapy should be initiated with 2 first-line drugs from different classes either as separate drugs or in a fixed-dose combination in persons with a blood pressure of 140/90 mm Hg and higher or with a blood pressure 20/10 mm and higher Hg above their blood pressure target.4
The first antihypertensive drug used to treat white and other non-black adults younger than 60 years of age with primary hypertension, should be an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB).4 The second drug used should be a thiazide diuretic (preferably chlorthalidone) or a calcium channel blocker (CCB). If a third antihypertensive drug is needed to control the hypertension, an ACE inhibitor or ARB plus a thiazide diuretic plus a CCB should be used.4 The first antihypertensive drug used to treat white and other non-black adults aged 60 years of age and older with primary hypertension should be a thiazide diuretic (preferably chlorthalidone) or a CCB.4 If a third antihypertensive drug is needed to control the hypertension, a thiazide diuretic plus a CCB plus an ACE inhibitor or ARB should be used.4 The first antihypertensive drug used to treat black adults with primary hypertension should be a thiazide diuretic (preferably chlorthalidone) or a CCB.4 If a third antihypertensive drug is needed to control the hypertension, a thiazide diuretic plus a CCB plus an ACE inhibitor or ARB should be used.4
Persons with hypertension and stable coronary heart disease should be treated with a beta blocker plus an ACE inhibitor or ARB.1,3,4,6-8 If a third antihypertensive drug is needed to control the hypertension, a beta blocker plus an ACE inhibitor or ARB plus a thiazide diuretic or a CCB should be used.4 If a fourth antihypertensive drug is needed to adequately control hypertension, an aldosterone antagonist should be given.4 In persons with stable ischemic heart disease who have angina pectoris despite beta blocker therapy and persistent uncontrolled hypertension, a dihydropyridine CCB should be added.1,3,4,7 The beta blockers that should be used for treatment of hypertension in patients with coronary heart disease include carvedilol, metoprolol tartrate, metoprolol succinate, bisoprolol, nadolol, propranolol, and timolol.4 Atenolol should not be used.1,3.4,8,9 The nondihydropyridine CCBs verapamil and diltiazem are contraindicated if left ventricular systolic dysfunction is present.1,3,4 Carvedilol, metoprolol succinate, or bisoprolol are the beta blockers to be used if left ventricular systolic dysfunction is present.1,3,4,7, 8
If patients with an acute coronary syndrome have hypertension after treatment with a beta blocker plus an ACE inhibitor or ARB, a long-acting dihydropyridine CCB such as amlodipine or felodipine should be added.1,3 Aldosterone antagonists should be given to patients treated with beta blockers plus ACE inhibitors or ARBs after myocardial infarction with left ventricular systolic dysfunction and heart failure or diabetes mellitus if their serum potassium is less than 5.0 meq/L and if their serum creatinine is ≤2.5 mg/dL in men and ≤ 2.0 mg/dL in women.1,3,4,10
Patients with hypertension and heart failure with a decreased left ventricular ejection fraction (HFrEF) should be treated with carvedilol, metoprolol succinate, or bisoprolol plus an ACE inhibitor or ARB or preferably an angiotensin receptor -neprilysin inhibitor plus a diuretic and if necessary with an aldosterone antagonist.1,3,4,10,11 Nondihydropyridine CCBs are contraindicated in patients with HFrEF).1,3,4,11
Patients with hypertension and heart failure with a preserved left ventricular ejection fraction should have their volume overload treated with diuretics, their comorbidities treated, and their hypertension treated with a beta blocker plus an ACE inhibitor or ARB plus an aldosterone antagonist.3,4,11-13
Hypertensive adults with chronic kidney disease stage 3 or higher or stage 1 or 2 chronic kidney disease with albuminuria ≥300 mg per day should be given an ACE inhibitor to slow progression of their chronic kidney disease.4, 14 If an ACE inhibitor is not tolerated, an ARB should be used.4 Patients with stage 1 or 2 chronic kidney disease without albuminuria may be given usual first-line antihypertensive drugs.4 If 3 antihypertensive drugs are necessary, an ACE inhibitor or ARB plus a thiazide diuretic plus a CCB4 are the preferred choices. After kidney transplantation, hypertension should be treated with a CCB to improve glomerular filtration rate and kidney survival.4,15
Hypertensive patients with a prior stroke or transient ischemic attack should be treated with a thiazide diuretic or ACE inhibitor or ARB.4, 16 If a third antihypertensive drug is needed , they should be receive a thiazide diuretic plus an ACE inhibitor or ARB plus a CCB.4
Thiazide diuretics, ACE inhibitors, ARBs, and CCBs may be used as initial treatment in hypertensive diabetics.4, 17-19 ACE inhibitors or ARBs should be given to hypertensive diabetics with persistent albuminuria.4,20
Beta blockers are the preferred antihypertensive drugs in hypertensive patients with a thoracic aortic aneurysm.4,21 Beta blockers also improve survival in patients with type A and with type B acute and chronic thoracic aortic dissection.4,22,23 Pregnant women with hypertension should be treated with methyldopa, nifedipine, and/or labetalol.4,24
Wilbert S. Aronow, MD, FACC and Julio A. Panza, MD, FACC
Division of Cardiology, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
- Aronow WS, Fleg JL, Pepine CJ, et al. ACCF/AHA 2011 expert consensus document on hypertension in the elderly: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. Developed in collaboration with the American Academy of Neurology, American Geriatrics Society, American Society for Preventive Cardiology, American Society of Hypertension, American Society of Nephrology, Association of Black Cardiologists, and European Society of Hypertension. J Am Coll Cardiol. 2011; 57: 2037-2114.
- Aronow WS. Lifestyle measures for treating hypertension. Arch Med Sci 2017; 13: 1241-1243.
- Rosendorff C, Lackland DT, Allison M, Aronow WS, et al. AHA/ACC/ASH scientific statement. Treatment of hypertension in patients with coronary artery disease: a scientific statement from the American Heart Association, American College of Cardiology, and American Society of Hypertension. J Am Coll Cardiol 2015; 65:1998-2038.
- 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; 70: xxx-xxx PMID 29146535
- Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014; 63: 2935-2959.
- Law MR, Morris JK, Wald NJ. Use of BP lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ 2009; 338:b1665.doi.10.1136/bmj.b1665.
- Smith SC Jr, 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. Endorsed by the World Heart Federation and the Preventive Cardiovascular Nurses Association. J Am Coll Cardiol 2011; 58: 2432-2446.
- Aronow WS. Current role of beta blockers in the treatment of hypertension. Expert Opin Pharmacotherap 2010; 11:2599-2607.
- Carlberg B, Samuelson O, Lindholm LH. Atenolol in hypertension: is it a wise choice? Lancet 2004; 364: 1684-1689.
- Pitt B, White H, Nicolau J, et al. Eplerenone reduces mortality 30 days after randomization following acute myocardial infarction in patients with left ventricular systolic dysfunction and heart failure. J Am Coll Cardiol 2005; 46:425-431.
- Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused 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. Developed in collaboration with the American Academy of Family Physicians, the American College of Chest Physicians, and International Society for Heart and Lung Transplantation. J Am Coll Cardiol 2017; 70: 776-803.
- Aronow WS, Ahn C, Kronzon I. Effect of propranolol versus no propranolol on total mortality plus nonfatal myocardial infarction in older patients with prior myocardial infarction, congestive heart failure, and left ventricular ejection fraction > or = 40% treated with diuretics plus angiotensin-converting enzyme inhibitors. Am J Cardiol 1997; 80: 207-209.
- Pfeffer MA, Claggett B, Assmann SF, et al. Regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. Circulation 2015; 131: 34-42.
- Wright JT Jr, Bakris G, Greene T, et al. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. JAMA 2002; 288: 2421-2431.
- Cross NB, Webster AC, Masson P, et al. Antihypertensives for kidney transplant recipients: systematic review and meta-analysis of randomized controlled trials. Transplantation 2009; 88: 7-18.
- PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358: 1033-1041.
- Turnbull F, Neal B, Algert C, et al. Effects of different blood pressure-lowering regimens on major cardiovascular events in individuals with and without diabetes mellitus: results of prospectively designed overviews of randomized trials. Arch Intern Med 2005; 165: 1410-1419.
- Emdin CA, Rahimi K, Neal B, et al. Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis. JAMA 2015; 313: 603-615.
- Whelton PK, Barzilay J, Cushman WC, et al. Clinical outcomes in antihypertensive treatment of type 2 diabetes, impaired fasting glucose concentration, and normoglycemia: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Arch Intern Med 2005; 165: 1401-1409.
- Palmer SC, Mavridis D, Navarese E, et al. Comparative efficacy and safety of blood pressure-lowering agents in adults with diabetes and kidney disease: a network meta-analysis. Lancet 2015; 385: 2047-2056.
- Hiratzka LF, Bakris GL, Beckman JA, et al. ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with thoracic aortic disease. J Am Coll Cardiol 2010; 55: e27-e129
- Genoni M, Paul M, Jenni R, et al. Chronic beta-blocker therapy improves outcome and treatment costs in chronic type B aortic dissection. Eur J Cardiothorac Surg 2001; 19: 606-610.
- Suzuki T, Isselbacher EM, Nienaber CA, et al. Type-selective benefits of medications in treatment of acute aortic dissection (from the International Registry of Acute Aortic Dissection (IRAD). Am J Cardiol 2012; 109: 122-127.
- James PR, Nelson-Piercy C. Management of hypertension before, during, and after pregnancy. Heart 2004; 90: 1499-1504.