Can people with heart disease take an angiotensin receptor blocker (ARB)?

The renin-angiotensin-aldosterone system is a key component in the development of cardiovascular disease and high blood pressure.^1-4 Heart failure (HF) management guidelines recommend the inhibition of angiotensin by an angiotensin converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB) is a key component of the treatment plan for people with hypertension and heart failure with reduced ejection fraction (HFrEF).^2,3,5 Some studies have shown ARBs may reduce HF hospitalizations and death in people with HFrEF and have less incidence of cough or angioedema side effects than ACEI.^6-11

The 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guidelines recommend:¹²

• 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)].
• 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)].
• 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)].

The 2016 ACC/AHA updated guidelines for the treatment of HF 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 systolic HF.³

Two ARBs, candesartan and valsartan, are FDA approved to treat HF with left ventricular systolic dysfunction (ejection fraction ≤ 40%).^8,13

The Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) Alternative study randomized 2,028 patients with symptomatic HF and left-ventricular ejection fraction ≤40% who were not taking ACEIs because of previous intolerance between candesartan (target dose 32 mg once daily) or matching placebo.¹⁴ Median follow-up was 33.7 months. During this time, 334 (33%) of 1,013 patients taking candesartan and 406 (40%) of 1,015 taking a placebo experienced cardiovascular death or first hospital admission for congestive HF (unadjusted hazard ratio 0.77, 95% confidence interval [CI] [0.67 – 0.89], p=0.0004; covariate adjusted 0.70 [0.60 – 0.81], p<0.0001). People discontinued the study and drug at similar rates between the candesartan (30%) and placebo (29%) groups.

However, a 2012 Cochrane review of 24 randomized trials of ARBs in patients with HF (n=25,051) found no reduction in total mortality or total hospitalizations when studies of candesartan and valsartan were pooled.⁴ It also found hospitalizations for HF were marginally reduced statistically with ARBs, but this was offset by a significantly higher risk of hospitalization for other causes for all HF patients on ARB compared to placebo (risk ratio [RR] 1.06, 95% CI [1.01 – 1.12]; absolute risk increase [ARI]=1.4%; number needed to harm [NNH]=72), irrespective of left ventricular ejection fraction. The early withdrawal from studies due to adverse events was also significantly higher in the ARB group than placebo (RR 1.19, 95% CI [1.09 – 1.30]; ARI=1.4%; NNH=72).

Manufacturers recommend monitoring renal function and potassium levels in people with heart failure taking ARBs.^15-23

^References

1. 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.
2. 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.
3. 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.
4. Heran BS, Musini VM, Bassett K, Taylor RS, Wright JM. Angiotensin receptor blockers for heart failure. Cochrane Database Syst Rev 2012; (4): Cd003040.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. Angiotensin II receptor antagonists. Drug Facts and Comparisons [online database]. Wolters Kluwer Health, Inc; 2017. Accessed May 17, 2017.
14. Granger CB, McMurray JJ, Yusuf S, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet 2003; 362 (9386): 772-776.
15. Atacand [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2016.
16. Diovan [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2017.
17. Benicar [package insert]. Parsippany, NJ: Daiichi Sankyo, Inc; 2009.
18. Micardis [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2014.
19. Teveten [package insert]. North Chicago, IL: AbbVie Inc.; 2014.
20. Cozaar [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp; 2015.
21. Avapro [package insert]. Bridgewater, NJ: Sanofi-Aventis U.S. LLC; 2016.
22. Edarbi [package insert]. Atlanta, GA: Arbor Pharmaceuticals, LLC; 2016.
23. Angiotensin II receptor antagonists. AHFS Drug Information [online database]. Gerald K. McEvoy PD, ed. 59th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2017.