1. Cardiovascular death and first heart failure hospitalization was reduced among HFrEF patients compared to HFmrEF and HFpEF patients.

2. Total heart failure hospitalizations were reduced in HFrEF compared to the other groups.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Mineralocorticoid receptor antagonists (MRAs) reduce hospitalizations and mortality in patients with heart failure with reduced ejection fraction (HFrEF). However, their effect in those with mildly reduced or preserved ejection fraction (HFmrEF and HFpEF, respectively) is debatable. This meta-analysis aimed to evaluate the effect of MRAs on cardiovascular death and heart failure hospitalizations in patients with HFrEF, HFmrEF, and HFpEF. The primary outcome was time to first heart failure hospitalization or death, while key secondary outcomes were total heart failure hospitalizations and all-cause mortality. According to study results, MRAs significantly reduced cardiovascular death and hospitalizations in HFrEF patients. MRAs also reduced the rate of hospitalizations in patients with HFmrEF and HFpEF. Although this study was well done, it was limited by a higher risk of hyperkalemia associated with MRA.

Click to read the study in The Lancet

Relevant Reading: Empagliflozin in Heart Failure with a Preserved Ejection Fraction

In-depth [randomized-controlled trial]: 13,846 patients were included across 4 trials (RALES, EMPHASIS-HF, TOPCAT, and FINEARTS-HF). Included were heart failure patients with a range of ejection fractions, from HFrEF to HFmrEF and HFpEF. The primary outcome of cardiovascular death or first heart failure hospitalization showed a significant reduction with MRAs, particularly in HFrEF patients (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.59-0.73], with a smaller but still beneficial effect in HFmrEF and HFpEF patients (HR 0.87, 95% CI 0.79-0.95). The secondary outcome of total heart failure hospitalizations also showed reductions in both HFrEF (HR 0.73, 95% CI 0.65-0.83) and HFmrEF/HFpEF groups (HR 0.92, 95% CI 0.80-1.05). However, cardiovascular death was not significantly reduced in the latter group. Findings from this study suggest that MRAs effectively reduce cardiovascular risk across the spectrum of heart failure, with the greatest benefit seen in those with reduced ejection fraction.

Image: PD

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