Heart failure & cardiomyopathiesSecondary analysis
Spironolactone, early acute estimated glomerular filtration rate (eGFR) changes, and clinical outcomes in patients with heart failure with preserved ejection fraction: insights from TOPCAT Americas
- Post-hoc analysis of the TOPCAT randomised trial (Americas)
- landmark analyses
Authors' conclusion
Early acute eGFR changes were common and adversely prognostic in patients with HFpEF. Spironolactone treatment was beneficial in improving cardiovascular outcomes, despite a modest increase in the likelihood of acute eGFR decrease.
Study context
- Population
- Patients with heart failure with preserved ejection fraction (HFpEF) enrolled in TOPCAT (Americas regional subgroup)
- Participants
- 1,648 patients
- Comparison
- Spironolactone vs placebo, by early eGFR dip
- Primary endpoint
- Early eGFR dip (≥15% decrease in eGFR, baseline to week 4) and its association with treatment and the primary composite endpoint (CV death, HF hospitalization or aborted cardiac arrest)
- Follow-up
- Week 4
Primary result
Early acute eGFR decrease (≥15%) · within 4 weeks
Odds ratio
1.97
95% CI 1.58–2.47
Events by treatment group
Spironolactone vs Placebo
OR 1.97 (95% CI 1.58–2.47)
As reported in the abstract
- Overall early acute eGFR decrease
- 431 (26%)
Further findings
| Outcome | HR (CI) | |
|---|---|---|
| Primary composite CV outcome, by early eGFR decrease (subgroup) — Spironolactone vs Placebo · with early eGFR decrease | 0.75 (0.53–1.08) | |
| Primary composite CV outcome, by early eGFR decrease (subgroup) — Spironolactone vs Placebo · without early eGFR decrease | 0.80 (0.64–1.00) | |
| 0.512Hazard ratio (log scale) |
- Primary composite CV outcome, by early eGFR decrease (subgroup): interaction P=.81
Prognosis of acute eGFR decrease
- Independently associated with higher risk of subsequent CV outcomes, irrespective of treatment arm
Primary endpoint across magnitude of eGFR decline
- Risk consistently lower with spironolactone vs placebo at any magnitude of eGFR decline
- P for interaction = 0.64
- interaction P=.64
Original publication
Spironolactone, early acute eGFR changes, and clinical outcomes in patients with heart failure with preserved ejection fraction: insights from TOPCAT Americas. Eur J Heart Fail. Published 8 April 2026. doi:10.1093/ejhf/xuag099
Summarised from the published abstract; every number is checked against it