ARBs may offer same efficacy, better tolerability than ACE inhibitors

Angiotensin-receptor blockers (ARBs) may be as efficacious and safe as angiotensin-converting enzyme (ACE) inhibitors in patients without heart failure, with the added advantage of better tolerability, a meta-analysis found.

Researchers reviewed randomized trials done from January 1980 through April 2015 of ACE inhibitors and ARBs compared with placebo or active controls, then corroborated outcomes with head-to-head trials of ARBs versus ACE inhibitors. Outcomes were all-cause mortality, cardiovascular death, myocardial infarction, angina, stroke, heart failure, revascularization, new-onset diabetes, end-stage renal disease, doubling of serum creatinine level, hyperkalemia, and drug withdrawal due to adverse events.

Results appeared in the January 2016 Mayo Clinic Proceedings.

The meta-analysis included 106 randomized trials that enrolled 254,301 patients. Compared with placebo, ACE inhibitors but not ARBs reduced the outcomes of all-cause mortality (ACE inhibitors vs. placebo: relative risk [RR], 0.89, 95% CI, 0.80 to 1.00; ARBs vs. placebo: RR, 1.01, 95% CI, 0.96 to 1.06; P=0.04 for the interaction), cardiovascular death (ACE inhibitors vs. placebo: RR, 0.83, 95% CI, 0.70 to 0.99; ARBs vs. placebo: RR, 1.02, 95% CI, 0.92 to 1.14; P=0.05 for the interaction), and myocardial infarction (ACE inhibitors vs. placebo: RR, 0.83, 95% CI, 0.78 to 0.90; ARBs vs. placebo: RR, 0.93, 95% CI, 0.85 to 1.03; P=0.06 for the interaction).

Meta-regression analysis showed that the difference between ACE inhibitors and ARBs compared with placebo was due to a higher placebo event rate in the ACE inhibitor trials for the outcome of all-cause mortality (P=0.001), cardiovascular death (P<0.001), and myocardial infarction (P=0.02). Researchers noted that most of the ACE inhibitor trials were conducted a decade earlier than the ARB trials. Sensitivity analyses restricted to trials published after 2000 revealed similar outcomes with ACE inhibitors versus placebo and ARBs versus placebo (P>0.05 for the interaction). Head-to-head comparison trials of ARBs and ACE inhibitors 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 to 0.81).

The researchers noted that treatment of cardiovascular disease changed considerably during the decade between ACE trials, which were conducted before 2000, and ARB trials, which were conducted after 2000, with the majority after 2005.Today, there is more aggressive use of statins and antihypertensives and aggressive cardiovascular risk factor control, including lower rates of smoking in trials conducted after 2000 than in trials conducted before 2000.

“The results of this study have significant clinical implications, in that it widens the choice of RAS [renin-angiotensin system] blockade from an ACE [inhibitor]-first approach to either ACE [inhibitors] or ARBs in patients without heart failure,” the authors wrote. “This is especially important given that most of the ARBs are also generic (and hence reducing cost) and, as a class, are better tolerated than ACE [inhibitors].”