Safety and efficacy of early initiation of mineralocorticoid receptor antagonist after an acute decompensated heart failure event or acute myocardial infarction with cardiac dysfunction: a meta-analysis of randomized clinical trials

Abstract

Background and aims: To conduct a meta-analysis of randomized controlled trials (RCTs) to evaluate the impact of mineralocorticoid receptor antagonists (MRAs) initiation in patients with heart failure (HF) within a few weeks after a decompensation event or acute myocardial infarction with cardiac dysfunction.

Methods: Four electronic databases were screened for eligible studies. Randomized controlled trials were included if they assessed MRA initiation either during an index hospitalization for HF or within 60 days following a first episode of HF decompensation or acute myocardial infarction with newly documented left ventricular dysfunction (i.e. <50%). When RCTs did not fulfil the eligibility criteria, subgroup analyses were examined and included if eligible. Efficacy endpoints were all-cause death, worsening HF, and length of hospital stay. Safety endpoints included worsening renal failure, hypokalaemia, and hyperkalaemia. A pre-specified subgroup analysis for efficacy endpoints was planned by clinical setting (acute ischaemic vs non-ischaemic HF). Six RCTs with 9770 patients were included.

Results: Early MRA use was associated with a significantly lower risk of hypokalaemia [risk ratio (RR) 0.39, 95% confidence interval (CI) 0.26-0.58], without increasing the risk of worsening renal failure or hypotension, but with a modest increase in hyperkalaemia risk. Mineralocorticoid receptor antagonist initiation within 60 days after decompensation significantly reduced the risk of all-cause death (RR 0.87, 95% CI 0.79-0.95) and worsening HF (RR 0.81, 95% CI 0.72-0.91), with no effect on hospital length, when compared with usual care. These benefits were consistent in acute ischaemic vs non-ischaemic HF.

Conclusions: Early MRA initiation was associated with improved prognosis when compared with usual care, though accompanied by an increased risk of hyperkalaemia, warranting close follow-up after initiation.

Prospero registration number: CRD42025649719.

Keywords: Acute heart failure; Early initiation; Mineralocorticoid receptor antagonist.