Spironolactone may not reduce CV mortality and hospitalizations in patients with HFpEF or HFmrEF: SPIRIT-HF Trial

These findings from the SPIRIT-HF trial were presented at the American College of Cardiology’s Annual Scientific Session (ACC.26) in March 2026

Heart failure with preserved ejection fraction (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF) present complex management challenges involving impaired cardiac relaxation and pumping; although spironolactone—a diuretic that blocks aldosterone and modifies heart tissue—is effective in cases of heart failure with reduced ejection fraction (HFrEF), prior findings from the TOPCAT trial remained inconclusive due to regional variations, leading Frank Edelmann, MD, chair of cardiovascular prevention at the Heart Center of Charité University Medicine, Berlin, to investigate whether this therapy could truly address the clinical gap in outcomes for these patients.

The SPIRIT-HF trial utilized a randomized, placebo-controlled design involving 730 symptomatic patients with a median age of 78 years across 56 European centers to evaluate the impact of spironolactone over a 24-month period. This study aimed to determine the efficacy of the drug against a placebo by measuring a primary composite endpoint of cardiovascular-related death and heart failure hospitalizations, while secondary assessments included monitoring for renal dysfunction, hypotension, and hyperkalemia to identify potential safety risks in this elderly population.

Key Clinical Findings of the Study Include:

• Primary Outcome: The SPIRIT-HF trial found no statistical difference in the primary composite endpoint, recording 12.7 events per 100 patient-years for spironolactone versus 10.8 for the placebo.

• Safety Profile: Clinicians noted a significant increase in adverse renal events, low blood pressure, and elevated potassium levels among participants receiving the active treatment.

• Hospitalization Trends: Unexpectedly, the study recorded a higher rate of total hospitalizations and a trend toward more cardiovascular-related hospital stays in the spironolactone arm.

• Subgroup Analysis: Results remained consistently negative across all demographics, showing no benefit regardless of the patient’s age, gender, or specific ejection fraction.

• Pandemic Influence: The investigation faced significant hurdles as over half of the treatment group stopped their medication due to the logistical constraints of the COVID-19 pandemic.

The results suggest that spironolactone does not provide a significant reduction in the composite of cardiovascular death and heart failure hospitalizations, as the treatment group ultimately surpassed the event rates of the placebo group with 12.7 versus 10.8 events per 100 patient-years by the end of the 24-month follow-up period.

Thus, the study concludes physicians should exercise caution and prioritize the monitoring of renal function and electrolyte levels when managing patients with these specific heart failure phenotypes.

Although the high rate of drug discontinuation during the pandemic potentially limited the trial’s ability to show definitive differences, further evidence from ongoing registry studies is required to fully understand the long-term safety and efficacy of this treatment.

Reference

American College of Cardiology. Study Finds No Significant Benefit of Spironolactone in HFpEF or HFmrEF. Presented at: American College of Cardiology’s Annual Scientific Session (ACC.26); March 29, 2026; New Orleans, LA.