MRAs appear effective for heart failure across the range of ejection fractions
Steroidal mineralocorticoid receptor antagonists (MRAs) (e.g., spironolactone and eplerenone) reduced risk for cardiovascular death or heart failure hospitalization in patients with heart failure and reduced ejection fraction (EF), while nonsteroidal MRAs (e.g., finerenone) seemed beneficial in those with mildly reduced or preserved EF, an individual-patient level meta-analysis found.
Mineralocorticoid receptor antagonists (MRAs) are associated with improved outcomes in heart failure with preserved, reduced, and mildly reduced ejection fraction, a recent study found.
Researchers performed an individual-patient level meta-analysis of four trials that evaluated steroidal and nonsteroidal MRAs in patients with heart failure and differing ejection fractions. Two trials enrolled patients with reduced ejection fraction, and two trials enrolled patients with preserved or mildly reduced ejection fraction. Two trials evaluated spironolactone, one evaluated eplerenone, and one evaluated finerenone. The primary outcome of the meta-analysis was a composite of time to first hospitalization for heart failure or cardiovascular death. Safety outcomes included serum creatinine level, estimated glomerular filtration rate, serum potassium level, and systolic blood pressure. Results were published Sept. 1 by The Lancet.
The four trials included 13,846 patients. Overall, MRAs were associated with reduced risk of cardiovascular death or heart failure hospitalization (hazard ratio [HR], 0.77 [95% CI, 0.72 to 0.83]). Efficacy of MRAs was greater in heart failure with reduced ejection fraction (HFrEF) versus mildly reduced ejection fraction (HFmrEF) or preserved ejection fraction (HFpEF), with hazard ratios (HRs) of 0.66 (95% CI, 0.59 to 0.73) versus 0.87 (95% CI, 0.79 to 0.95). Both the trials that enrolled patients with HFrEF and those that enrolled patients with HFmrEF or HFpEF indicated significant reductions in heart failure hospitalization with MRAs (HRs, 0.63 [95% CI, 0.55 to 0.72] and 0.82 [95% CI, 0.74 to 0.91], respectively).
A reduction in cardiovascular death was seen in the HFrEF trials (HR, 0.72 [95% CI, 0.63 to 0.82]) but not the HFmrEF or HFpEF trials (HR, 0.92 [95% CI, 0.80 to 1.05]); this was also the case for all-cause death (HRs, 0.73 [95% CI, 0.65 to 0.83] and 0.94 [95% CI, 0.85 to 1.03], respectively). Risk of hyperkalemia increased substantially with an MRA versus placebo (odds ratio, 2.27 [95% CI, 2.02 to 2.56]), but rates of serious hyperkalemia, defined as a serum potassium level above 6.0 mmol/L, were low (2.9% vs. 1.4%). Risk for hypokalemia, defined as a serum potassium level below 3.5 mmol/L, was much lower with an MRA than with placebo (odds ratio, 0.51 [95% CI, 0.45 to 0.57]).
The researchers noted that their analysis was restricted to larger trials, that they could not directly compare steroidal and nonsteroidal MRAs, and that Black and Asian patients were underrepresented, among other limitations. “In conclusion, this meta-analysis of almost 14 000 patients across four large clinical trials provides comprehensive evidence that steroidal MRAs reduce the risk of cardiovascular death or heart failure hospitalization in patients with HFrEF and non-steroidal MRAs reduce this risk in HFmrEF or HFpEF,” they concluded. “These benefits were consistent across patient subgroups. Treatment with an MRA should be considered in all patients with heart failure who do not have a contraindication to this treatment.”