SPIRIT‑HF: Spironolactone Falls Short in HFpEF and HFmrEF

The SPIRIT‑HF trial, presented at ACC.26, found that spironolactone, an aldosterone blocker, did not reduce heart failure hospitalizations or cardiovascular death at 24 months in patients with HFpEF or HFmrEF, compared with placebo. 

The double‑blind, European study randomized 730 patients with symptomatic HFpEF or HFmrEF (median age ~78, half women, ~80% HFpEF) across 56 centers from 2018 to 2024.

The primary endpoint—a composite of HF hospitalization and cardiovascular death—showed 10.8 events per 100 patient‑years with placebo versus 12.7 with spironolactone, with no meaningful difference across subgroups by age, sex, ejection fraction, or comorbidities. 

Instead, the spironolactone arm had significantly more total hospitalizations, hypotension, renal events, and elevated potassium, and a trend toward more cardiovascular hospitalizations.

The trial was also limited by a high rate of drug discontinuation during the COVID‑19 pandemic, which reduced its power and makes the efficacy signal “negative or slightly inconclusive.” 

A meta‑analysis combining SPIRIT‑HF with the TOPCAT Americas cohort similarly showed no benefit from spironolactone.

 For clinicians, these data suggest that in routine HFpEF/HFmrEF management, spironolactone should be used cautiously, with close monitoring of renal function and potassium, and that other mechanisms and agents deserve focus in this population.