All angiotensin receptor blockers (ARBs) are approved by the Food and Drug Administration (FDA) to treat hypertension.1 Candesartan and valsartan are FDA approved to treat heart failure with left ventricular systolic dysfunction (ejection fraction ≤ 40%).1,2 Irbesartan and losartan are FDA approved to treat diabetic nephropathy in people with type 2 diabetes and hypertension.1
Hypertension
ARBs are listed in national and international guidelines as one of several classes of antihypertensive medications for the first-line management of hypertension.3-6 In the 2017 hypertension guidelines from the American College of Cardiology and American Heart Association (ACC/AHA), ARBs are listed along with calcium channel blockers (CCBs), angiotensin-converting-enzyme inhibitors (ACEIs), or thiazide-type diuretics as initial antihypertensive treatments in the general non-black population [Strong Recommendation (Level A-SR)].6
A 2016 meta-analysis was done of placebo-controlled trials (a meta-regression analysis restricted these trials after 2000), active controlled trials, and head-to-head randomized trials comparing two first-line antihypertensive monotherapies, ACEIs and ARBs, in patients without heart failure.7 This analysis looked at 106 randomized trials with 254,301 patients. It found that each significantly reduce the outcomes of all-cause mortality, cardiovascular death, and myocardial infarction (MI). The only difference found was that ARBs had a lower risk of drug withdrawal due to adverse side effects than ACEIs.
Heart Disease
The renin-angiotensin-aldosterone system (RAAS) is a key component in the development of cardiovascular disease and high blood pressure.5,8,9 Heart failure management guidelines recommend the inhibition of angiotensin by an ACEI or ARB is a key component of the treatment plan for people with hypertension and heart failure with reduced ejection fraction (HFrEF).5,9,10 Studies have shown ARBs may reduce heart failure hospitalizations and death in people with HFrEF and have less incidence of cough or angioedema side effects than ACEI.2,11-15
The 2017 ACC/AHA hypertension guidelines recommend:6
- Adults with stable ischemic heart disease and hypertension (BP ≥ 130/80 mm Hg) use ACEIs, ARBs, or beta blockers as first-line pharmacological therapy [Strong recommendation (Level B-R)].6
- Adults with HFrEF and hypertension should be prescribed ACEIs, ARBs, or beta blockers titrated to attain a BP of less than 130/80 mm Hg [Strong recommendation (Level C-EO)].6
- Adults with heart failure with preserved ejection fraction and persistent hypertension after management of volume overload should be prescribed ACEIs, ARBs, or beta blockers titrated to attain a systolic BP of less than 130 mm Hg [Strong recommendation (Level C-LD)].6
The 2016 ACC/AHA update to the 2013 guidelines find ARBs an acceptable alternative for people who are intolerant of ACEI due to cough or angioedema which are the primary choice for renin-angiotensin system inhibition for patients with heart failure with reduced ejection fraction [Strong recommendation (Level A)].9
Kidney Disease
Studies have shown the progression of kidney disease may be slowed by ARBs.16 The Kidney Disease: Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD) recommends that an ARB or ACEI be used in both diabetic and non-diabetic adults with CKD and urine albumin excretion >300 mg/24 hours.17 The guideline also suggests an ARB or ACEI be used in diabetic adults with CKD and urine albumin excretion 30 to 300 mg/24 hours.
The 2017 ACC/AHA hypertension guideline also recommends that adults with chronic kidney disease should include an ACEI as part of their antihypertensive treatment to improve kidney outcomes [Moderate Recommendation (Level B-R)] or an ARB if an ACEI is not tolerated [Weak Recommendation (Level C-EO)].6
A 2015 network meta-analysis found ARB monotherapy significantly reduced progression to end-stage renal disease in people with diabetes compared to placebo (odds ratio [OR] 0.77, 95% confidence interval [CI] [0.65 – 0.92]).16 Combination therapy with ARB and ACEI was superior (OR 0.62, 95% CI [0.43 – 0.90]), but this combination has some risk of increased hyperkalemia and acute kidney injury.
References
- Angiotensin II receptor antagonists. Drug Facts and Comparisons [online database]. Wolters Kluwer Health, Inc; 2017. Accessed May 17, 2017.
- 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 (9386): 759-766.
- James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults. JAMA 2014; 311 (5): 507-520.
- Qaseem A, Wilt TJ, Rich R, Humphrey LL, Frost J, Forciea MA. 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 (6): 430-430.
- Rosendorff C, Lackland DT, Allison M, et al. 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. Circulation 2015; 131 (19): e435-470.
- 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: executive summary: a reportof the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension 2017.
- Bangalore S, Fakheri R, Toklu B, Ogedegbe G, Weintraub H, Messerli FH. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in patients without heart failure? Insights from 254,301 patients from randomized trials. Mayo Clin Proc 2016; 91 (1): 51-60.
- Unger T. The role of the renin-angiotensin system in the development of cardiovascular disease. Am J Cardiol 2002; 89 (2a): 3A-9A; discussion 10A.
- 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. J Am Coll Cardiol 2016; 68 (13): 1476-1488.
- Yancy CW, Jessup M, Bozkurt B, 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. J Am Coll Cardiol 2013; 62 (16): e147-239.
- Cohn JN, Tognoni G. A Randomized Trial of the Angiotensin-Receptor Blocker Valsartan in Chronic Heart Failure. N Engl J Med 2001; 345 (23): 1667-1675.
- Pfeffer MA, McMurray JJV, Velazquez EJ, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003; 349 (20): 1893-1906.
- Konstam MA, Neaton JD, Dickstein K, et al. Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial. Lancet; 374 (9704): 1840-1848.
- Yusuf S, Teo K, Anderson C, et al. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. Lancet 2008; 372 (9644): 1174-1183.
- Yusuf S, Teo KK, Pogue J, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008; 358 (15): 1547-1559.
- 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 (9982): 2047-2056.
- KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl (2011) 2013; 3 (1): i-150.
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