August 8, 2021Open Access
A Composite Metric for Predicting Benefit from Spironolactone in Heart Failure with Preserved Ejection Fraction
Key Result
In patients with heart failure with preserved ejection fraction, a higher Trial Score (≥1.14) predicted significant clinical benefit from spironolactone (βinteraction = -0.28, P < 0.01).
Study Design
Type
Observational (n=3,820)
Multicenter
Yes
Structured PICO
Does a composite Trial Score predict clinical benefit from spironolactone in patients with heart failure with preserved ejection fraction?
P
Population
3,820 patients with heart failure with preserved ejection fraction (HFpEF), including 3,443 participants from the TOPCAT trial (1,766 from the Americas, 1,677 from Eastern Europe) and 377 patients from a real-world US registry.
I
Intervention
Spironolactone (evaluated via a novel 9-component Trial Score to predict likelihood of benefit)
C
Comparator
Placebo (in the TOPCAT trial cohort)
O
Outcome
Composite of cardiovascular mortality, aborted cardiac arrest, or heart failure hospitalizationcomposite
A novel composite Trial Score based on 9 routine clinical variables can identify patients with HFpEF who are most likely to derive clinical benefit from spironolactone therapy.
Main Result
Effect estimate: βinteraction -0.28
p-value: p=<0.01
Limitations
- Retrospective analysis of the TOPCAT trial
- Trial Score is limited to baseline characteristics that are continuous variables
- Categorical variables like sex and race are not included
- Has not yet been prospectively studied in a trial
Abstract
AIMS: The TOPCAT trial showed no benefit for spironolactone in heart failure patients with preserved ejection fraction (HFpEF). Post-hoc, spironolactone helped participants from the Americas, but not Eastern Europe. Determining which patients with HFpEF could respond like TOPCAT's responders should help guide their care. We aimed to develop a TOPCAT Trial Score (TS) as a composite metric to identify such patients. METHODS AND RESULTS: FPEF scores (≥3). The cohort of real-world patients with HFpEF had even higher TS than American TOPCAT participants. CONCLUSIONS: Patients with HFpEF can be quantified by the TS to capture the likelihood of benefit from spironolactone.