Heart failure & cardiomyopathiesSecondary analysis
An Individual Treatment Effect Approach to Predict Response to Mineralocorticoid Receptor Antagonists in Patients with Heart Failure and Reduced Ejection Fraction
- Secondary analysis of the RALES, EMPHASIS-HF and EPHESUS randomised trials (prediction model development and validation)
- counterfactual random forest
- linear regression individual treatment effect (ITE) prediction model
- external validation in EPHESUS
Authors' conclusion
In HFrEF across various clinical settings, our simple ITE model predicted individual responses to MRA therapy.
Study context
- Population
- Patients with HFrEF (derivation: RALES and EMPHASIS-HF); validation: LV systolic dysfunction and/or heart failure (HF) after MI (EPHESUS)derivation
- Participants
- 3,887 patients
- Comparison
- MRA vs placebo
- Primary endpoint
- CV death or HF hospitalization
- Follow-up
- 2-year period
Primary result
As reported in the abstract
CV death or HF hospitalization: MRA treatment effect by ITE score (RALES and EMPHASIS-HF, n = 3887) · 2 years
Each group vs placeboHazard ratio (95% CI)
ITE score 5
0.82(0.67–1.02)
ITE score 20
0.47(0.35–0.63)
Further findings
Validation in EPHESUS
- Similar pattern: greater treatment effects with higher ITE scores
- p for interaction = 0.007
Original publication
An Individual Treatment Effect Approach to Predict Response to Mineralocorticoid Receptor Antagonists in Patients with Heart Failure and Reduced Ejection Fraction. Eur J Heart Fail. Published 16 September 2025. doi:10.1002/ejhf.70047
Summarised from the published abstract; every number is checked against it