Spironolactone in Heart Failure
Spironolactone in Heart Failure With Preserved or Mildly Reduced Ejection Fraction (SPIRIT-HF)
Presented by Frank Edelmann — Charite - Universitatsmedizin Berlin
Subspecialty: Heart Failure
Published in ACC.26 Late-Breaking
Key Result
Spironolactone did NOT significantly reduce HF hospitalizations or CV death in HFpEF/HFmrEF (12.7 vs 10.8 events per 100 patient-years). Unexpected increase in total hospitalizations, hypotension, and renal dysfunction in the spironolactone group.
What did this trial find?
The SPIRIT-HF trial randomized 730 patients with HFpEF or HFmrEF to spironolactone vs placebo and found no significant reduction in HF hospitalizations or CV death at 24 months. Unexpectedly, spironolactone was associated with increased total hospitalizations, hypotension, and renal dysfunction. The trial enrolled only half its planned patients due to COVID-19 disruptions, leaving it underpowered. Coverage reflects genuine interpretive debate about whether the results are truly negative or merely inconclusive, with safety signals drawing particular attention.
Why does this trial matter?
There is genuine interpretive debate here. The trial's underpowered status creates real uncertainty about whether the null result reflects true lack of efficacy or insufficient power. The unexpected safety signal of increased total hospitalizations adds a meaningful wrinkle. Bozkurt's outside commentary directly challenges the ability to draw any efficacy conclusions. However, quote supply is limited to essentially two named experts — the lead author and one outside commentator.
Study Design
Double-blind, placebo-controlled, randomized trial across 56 centers in 4 European countries (N=730)
Clinical Implications
Spironolactone's benefit in HFpEF/HFmrEF remains uncertain. The unexpected increase in hospitalizations and renal events warrants caution. Trial was underpowered due to COVID-related enrollment challenges.
Abstract
The SPIRIT-HF trial was a double-blind, placebo-controlled trial that randomized 730 patients across 56 centers in 4 European countries from 2018-2024. About 80% had HFpEF and 20% had HFmrEF, with median age nearly 78 years and approximately half women. At 24 months, the primary composite endpoint (HF hospitalization and CV death) showed no significant difference: 12.7 events per 100 patient-years with spironolactone vs 10.8 with placebo. The spironolactone group showed significantly higher rates of total hospitalizations, hypotension, renal dysfunction, and elevated potassium levels, with a trend toward increased CV hospitalizations. The trial enrolled only about half its planned patients due to high discontinuation from COVID-19, making it underpowered.