At this year’s congress of the American College of Cardiology (ACC.26) in March 2026 in New Orleans, the results of the SPIRIT-HF study were presented in the Late-Breaking Clinical Trials session. The study, funded by the German Centre for Cardiovascular Research (DZHK), investigated whether spironolactone provides clinical benefit in patients with heart failure with preserved (HFpEF) or mildly reduced ejection fraction (HFmrEF).
Evidence gap in the treatment of HFpEF
The background of the study is a long-standing evidence gap: while mineralocorticoid receptor antagonists (MRAs) such as spironolactone are well established in heart failure with reduced ejection fraction, their benefit for the large and growing group of HFpEF and HFmrEF patients has remained unclear. The largest prior study, TOPCAT trial, produced conflicting results. SPIRIT-HF aimed to provide a robust answer to this question for the first time in a European, randomized, double-blind design.
Between 2018 and 2024, the study enrolled a total of 730 patients at 56 centers in Germany, the Netherlands, Austria, and France. The median age of participants was 76 years, about half were women, around 80% had HFpEF and 20% HFmrEF. The primary endpoint—a composite of cardiovascular death and heart failure hospitalizations within 24 months after starting therapy—was not significantly affected by spironolactone compared with placebo.
“SPIRIT-HF was unable to definitively test its primary hypothesis due to insufficient sample size and the low number of events resulting from the premature termination of the trial. Nevertheless, the data provide insights into the efficacy and safety of spironolactone in this patient group that the medical community must discuss,” said study lead Frank Edelmann (German Heart Center of the Charité); co-lead investigator was Burkert Pieske (University Medicine Rostock).
The limited interpretability of the study is largely attributable to the COVID-19 pandemic, during which recruitment was not possible and study visits were canceled. Resulting financial difficulties—particularly for manufacturing new study medication—ultimately led to early termination of the trial, meaning only about half of the originally planned patient number was reached. SPIRIT-HF is therefore statistically underpowered.
The study was overseen by an international steering committee, which included Stefan Anker as a leading member; statistical design and analysis were conducted under the direction of Tim Friede (University Medicine Göttingen).
Positive signals from TOPCAT not confirmed
A pre-specified meta-analysis combining SPIRIT-HF data with the TOPCAT Americas cohort also showed no significant effect. Thus, the positive signals observed in the TOPCAT Americas cohort could not be confirmed by the new data. However, an increased rate of hospitalizations was observed in the spironolactone group.
The full study results will be published soon in an international peer-reviewed journal. Further insights into the role of spironolactone in HFpEF are expected from the ongoing registry-based SPIRRIT-HFpEF study in Sweden and the United States.
Study:
SPIRonolactone In the Treatment for Heart Failure (SPIRIT-HF-DZHK8)
