In patients on conventional
heart failure therapy including
angiotensin-converting enzyme (
ACE) inhibitors, the addition of
angiotensin receptor blockers (ARBs),
direct renin inhibitors (DRIs), or
aldosterone antagonists are therapeutic options to further reduce the risk of cardiovascular events. However, whether one is preferable over the other is not known. PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched for randomized clinical trials (RCTs), until March 2011, of trials testing either an ARB, DRI, or an
aldosterone antagonist in patients with
heart failure who were on conventional
heart failure therapy with follow-up of at least 3 months. Efficacy (death, cardiovascular death, nonfatal
myocardial infarction,
heart failure hospitalization and composite of cardiovascular death or
heart failure hospitalization) and safety (
hyperkalemia,
hypotension,
renal failure) outcomes were compared. The authors identified 16 RCTs involving 31,429 participants that satisfied the inclusion criteria. When compared with placebo (reference rate ratio [RR] of 1),
aldosterone antagonists reduced the rate of death (RR, 0.79; 95% credibility interval [CrI], 0.66-0.98), cardiovascular death (RR, 0.78; 95% CrI, 0.65-0.93),
heart failure hospitalization (RR, 0.74; 95% CrI, 0.55-0.94), and the composite of cardiovascular death or
heart failure hospitalization (RR, 0.73; 95% CrI, 0.55-0.90) with no difference for other efficacy outcomes. However, ARBs and DRIs did not result in any significant reduction in the rate of any of the efficacy outcomes when compared with placebo. When compared with placebo (RR=1), ARBs increased the rate of
hyperkalemia (138% increase),
renal failure (126% increase), and
hypotension (63% increase). Similarly,
aldosterone antagonists resulted in a 110% increase in
hyperkalemia and DRIs with a 98% increase in
hypotension. In patients with
heart failure and reduced systolic function on conventional
heart failure medications, the risk benefit ratio favors the addition of
aldosterone antagonists over ARBs or DRIs.