Key result
Adding aldosterone antagonists to conventional heart failure therapy reduced the rate of death (RR 0.79; 95% CrI 0.66-0.98) compared with placebo, whereas ARBs and DRIs showed no significant reduction.
Why the study?
Does the addition of ARBs, DRIs, or aldosterone antagonists improve outcomes in patients with heart failure on conventional therapy including ACE inhibitors?
Meta-Analysis (n=31,429)
Does the addition of ARBs, DRIs, or aldosterone antagonists improve outcomes in patients with heart failure on conventional therapy including ACE inhibitors?
Effect estimate: RR 0.79 (95% CI 0.66-0.98)
In patients with HFrEF on conventional therapy, adding an aldosterone antagonist provides superior mortality and morbidity benefits compared to adding an ARB or DRI.
Clinicians should favor aldosterone antagonists over ARBs or DRIs when intensifying ACE inhibitor-based HFrEF therapy; confirms selective mortality benefit.
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.
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Bangalore et al. (2012) conducted a meta-analysis in Heart failure (n=31,429). Aldosterone antagonists, ARBs, or DRIs vs. Placebo was evaluated on Death (RR 0.79, 95% CI 0.66-0.98). Adding aldosterone antagonists to conventional heart failure therapy reduced the rate of death (RR 0.79; 95% CrI 0.66-0.98) compared with placebo, whereas ARBs and DRIs showed no significant reduction.
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