FPIN's Clinical Inquiries
Angiotensin-Converting Enzyme Inhibitors vs. Angiotensin Receptor Blockers
Am Fam Physician. 2015 Feb 1;91(3):193-194.
In which clinical situations are angiotensin receptor blockers (ARBs) preferred over angiotensin-converting enzyme (ACE) inhibitors?
ACE inhibitors should be used in patients with hypertension because they reduce all-cause mortality, whereas ARBs do not. (Strength of Recommendation [SOR]: A, based on a meta-analysis.) ARBs are preferred for patients who have adverse reactions to ACE inhibitors. (SOR: A, based on a meta-analysis.) ARBs cause less cough than ACE inhibitors, and patients are less likely to discontinue ARBs because of adverse effects. ACE inhibitors and ARBs may be used in patients with vascular disease or diabetes mellitus with end-organ damage because they produce equal reductions in mortality and hospital admissions. (SOR: B, based on a randomized controlled trial [RCT].)
A 2012 meta-analysis of 20 clinical trials involving 158,998 patients examined the effect of ACE inhibitors and ARBs in patients with hypertension.1 ACE inhibitors reduced all-cause mortality (hazard ratio [HR] = 0.90; 95% confidence interval [CI], 0.84 to 0.97; P = .004), whereas ARBs did not (HR = 0.99; 95% CI, 0.94 to 1.04; P = .683).
A 2012 meta-analysis of 12 RCTs evaluated the tolerability of ARBs in patients with previous ACE inhibitor intolerance due to cough, angioedema/anaphylaxis, hypotension, renal dysfunction, and hyperkalemia.2 Patients receiving ARBs were less likely to have cough (relative risk [RR] = 0.37; 95% CI, 0.28 to 0.48) compared with those receiving ACE inhibitors. The risks of hypotension (RR = 2.63; 95% CI, 1.77 to 3.92), renal dysfunction (RR = 2.07; 95% CI, 1.45 to 2.95), and hyperkalemia (RR = 3.37; 95% CI, 1.60 to 7.11) were higher among those receiving ARBs compared with placebo, but were not reported for those receiving ACE inhibitors.
Two RCTs and a meta-analysis assessed the safety of ARBs in patients with ACE inhibitor–induced angioedema.3–5 The first RCT included 75 patients who discontinued ACE inhibitors because of angioedema or anaphylaxis.3 Patients were randomized to 80 mg of telmisartan (Micardis) or placebo. One patient who was receiving placebo developed recurrence of angioedema. The second RCT included 39 patients who had heart failure and angioedema with ACE inhibitor use; they were randomized to 32 mg of candesartan (Atacand) per day or placebo.4 Three patients receiving candesartan (7.7%) developed angioedema. The meta-analysis included three studies that evaluated the risk of angioedema recurrence with the use of ARBs in 71 patients with prior ACE inhibitor–induced angioedema.5 Eight patients receiving ARBs (11.2%) developed recurrence of angioedema.
A double-blind RCT involving 25,620 patients with vascular disease or diabetes with end-organ damage compared three groups: patients receiving ramipril (Altace) alone, telmisartan alone, or a combination of both.6 The composite primary outcomes were equivalent in the telmisartan and the ramipril groups (RR = 1.01; 95% CI, 0.94 to 1.09), but the combination therapy resulted in higher mortality rates. Outcomes included death from cardiovascular disease, myocardial infarction, or stroke, and hospitalization for congestive heart failure. Patients receiving telmisartan had less cough (1.1% vs. 4.2%; P < .001) and angioedema (0.1% vs. 0.3%; P = .01), but more hypotension (2.6% vs. 1.7%; P < .001) compared with those receiving ramipril. Rates of renal impairment (RR = 1.04; 95% CI, 0.96 to 1.14) and syncope (RR = 1.27; P = .49) were equivalent in those treated with telmisartan or ramipril.
Recommendations from Others
The Eighth Joint National Committee recommends ACE inhibitors as an option for initial management of hypertension in patients who are not black, and recommends either an ACE inhibitor or an ARB in patients with chronic kidney disease.7 The National Institute for Health and Care Excellence recommends ACE inhibitors as first-line therapy for reducing blood pressure in patients with type 2 diabetes, but clinicians may substitute an ARB if the patient cannot tolerate ACE inhibitors (except if there is hyperkalemia or renal dysfunction).8
REFERENCESshow all references
1. Van Vark L, Bertrand M, Akkerhuis KM, et al. Angiotensin-converting enzyme inhibitors reduce mortality in hypertension: a meta-analysis of randomized clinical trials of renin-angiotensin-aldosterone system inhibitors involving 158,998 patients. Eur Heart J. 2012;33(16):2088–2097....
2. Caldeira D, David C, Sampaio C. Tolerability of angiotensin-receptor blockers in patients with intolerance to angiotensin-converting enzyme inhibitors: a systematic review and meta-analysis. Am J Cardiovasc Drugs. 2012;12(4):263–277.
3. 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 [published correction appears in Lancet. 2008;372(9647):1384]. Lancet. 2008;372(9644):1174–1183.
4. 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.
5. Haymore BR, Yoon J, Mikita CP, et al. Risk of angioedema with angiotensin receptor blockers in patients with prior angioedema associated with angiotensin-converting enzyme inhibitors: a meta-analysis. Ann Allergy Asthma Immunol. 2008;101(5):495–499.
6. 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.
7. 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) [published correction appears in JAMA. 2014;311(17):1809]. JAMA. 2014;311(5):507–520.
8. National Institute for Health and Care Excellence. Type 2 diabetes: the management of type 2 diabetes. NICE clinical guideline 87. http://www.nice.org.uk/guidance/cg87/resources/guidance-type-2-diabetes-pdf. Accessed September 15, 2014.
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Clinical Inquiries provides answers to questions submitted by practicing family physicians to the Family Physicians Inquiries Network (FPIN). Members of the network select questions based on their relevance to family medicine. Answers are drawn from an approved set of evidence-based resources and undergo peer review. The strength of recommendations and the level of evidence for individual studies are rated using criteria developed by the Evidence-Based Medicine Working Group (http://www.cebm.net/?o=1025).
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