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Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers in Patients Without Heart Failure? Insights From 254,301 Patients From Randomized Trials



      To compare the efficacy and safety of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) in patients without heart failure.

      Patients and Methods

      Meta-analysis of randomized trials identified using PubMed, Embase, and Cochrane Central Register of Controlled Trials searches from January 1, 1980, through April 13, 2015, of ACEis and ARBs compared with placebo or active controls and corroborated with head-to-head trials of ARBs vs ACEis. Outcomes were all-cause mortality, cardiovascular death, myocardial infarction (MI), angina, stroke, heart failure, revascularization, and new-onset diabetes.


      Our search yielded 106 randomized trials that enrolled 254,301 patients. Compared with placebo, ACEis but not ARBs reduced the outcomes of all-cause mortality (ACEis vs placebo: relative risk [RR], 0.89; 95% CI, 0.80-1.00; ARBs vs placebo: RR, 1.01; 95% CI, 0.96-1.06; Pinteraction=.04), cardiovascular death (RR, 0.83; 95% CI, 0.70-0.99 and RR, 1.02; 95% CI, 0.92-1.14; Pinteraction=.05), and MI (RR, 0.83; 95% CI, 0.78-0.90 and RR, 0.93; 95% CI, 0.85-1.03; Pinteraction=.06). The meta-regression analysis revealed that the difference between ACEis and ARBs compared with placebo was due to a higher placebo event rate in the ACEis trials (most of these trials were conducted a decade earlier than the ARB trials) for the outcome of all-cause mortality (P=.001), cardiovascular death (P<.001), and MI (P=.02). Sensitivity analyses restricted to trials published after 2000 revealed similar outcomes with ACEis vs placebo and ARBs vs placebo (Pinteraction>.05). Head-to-head comparison trials of ARBs vs ACEis exhibited no difference in outcomes except for a lower risk of drug withdrawal due to adverse effects with ARBs (RR, 0.72; 95% CI, 0.65-0.81).


      In patients without heart failure, evidence from placebo-controlled trials (restricted to trials after 2000), active controlled trials, and head-to-head randomized trials all suggest ARBs to be as efficacious and safe as ACEis, with the added advantage of better tolerability.

      Abbreviations and Acronyms:

      ACEi (angiotensin-converting enzyme inhibitor), ARB (angiotensin receptor blocker), CKD (chronic kidney disease), CVD (cardiovascular disease), ESRD (end-stage renal disease), MI (myocardial infarction), RAS (renin-angiotensin system), RR (relative risk)
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      Linked Article

      • The Different Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on Mortality
        Mayo Clinic ProceedingsVol. 91Issue 7
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          The article by Bangalore et al1 published in the January 2016 issue of Mayo Clinic Proceedings deals with the important topic of cardiovascular protection. In this regard, several recent studies have compared the 2 classes of cardioprotective drugs, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). As highlighted by Bangalore et al, these studies have often reported mortality reduction with ACE inhibitors vs placebo or comparators, while ARBs were not associated with significant effect.
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