Spironolactone failed to reduce major adverse cardiac effects in patients with CKD on haemodialysis

Spironolactone did not reduce the rate of major adverse cardiac events (MACE) for patients with chronic kidney disease (CKD) undergoing haemodialysis. An analysis of the individual components of the primary endpoint did show a significant reduction in the incidence of hospitalisation for heart failure.

Overactivation of the mineralocorticoid system plays a role in the pathology of cardiac disease and subsequent epidemiology of cardiac death in patients with CKD. “We, therefore, investigated the effects of the steroidal mineralocorticoid receptor antagonist spironolactone on cardiovascular outcomes in a high-risk haemodialysis population,” Prof. Patrick Rossignol (University Hospital of Nancy, France) described the overarching goals of the double-blind, randomised, placebo-controlled, phase 3 ALCHEMIST trial (NCT01848639) [1].

ALCHEMIST assessed the efficacy of spironolactone on MACE (defined as non-fatal myocardial infarction and acute coronary syndrome, hospitalisation for heart failure, non-fatal stroke, or cardiovascular-induced death) in haemodialysis patients with pre-existing cardiovascular risk. The primary endpoint was time to first event. The 644 participants recruited from 64 sites in 3 countries were randomised 1:1 to spironolactone or placebo for 4 weeks and had a follow-up period of 2–4 years. Doses were titrated up to 25 mg per day.

The primary endpoint was not met:  spironolactone did not reduce the time to first cardiac event (HR 0.996; 95% CI 0.729–1.362; P=0.982). An additional analysis showed that time to hospitalisation for heart failure was the only cardiac outcome that significantly favoured the spironolactone group compared with placebo (HR 0.412; 95% CI 0.171–0.995; P=0.049). A subgroup analysis of the primary outcome revealed a significant age effect, with individuals >75 years showing an increased likelihood of MACE compared with those ≤75 years (HR 1.50; 95% CI 0.93–2.41). Hyperkalaemia was slightly more prevalent in the spironolactone group compared with the placebo group (12.0% vs 9.8%).

1. Rossignol P, et al. ALdosterone Antagonist Chronic HEModialysis Interventional Survival Trial (ALCHEMIST): Primary Results. FR-OR113, ASN Kidney Week 2023, 2–5 November, Philadelphia, PA, USA.

 

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Posted on 28 November 202317 May 2024