Introduction:
Several clinical phenotypes have been described in patients with heart failure with preserved ejection fraction (HFpEF). This heterogeneity may explain why no therapies have improved outcomes in clinical trials of HFpEF patients. In a secondary analysis of TOPCAT, the authors discovered improved mortality in female HFpEF patients treated with spironolactone. The objective of this study was to determine if outcomes for spironolactone in women with HFpEF varied by female-specific phenotypes.
Methods:
Using 10 clinical variables, a latent class analysis (LCA) of 5196 female patients from 7 clinical trials (BEST, IPRESERVE, MOCHA, NEAT-HFpEF, RELAX, TOPCAT, and SOLVD) was used to identify phenotypes across the LVEF spectrum, which included 3 distinct phenotypes of HFpEF patients. A post-hoc analysis of TOPCAT was completed to analyze the outcomes of spironolactone versus placebo by female phenotype. The outcomes were cardiovascular (CV) mortality, heart failure (HF) hospitalizations, all-cause mortality, and CV hospitalizations.
Results:
Table 1 shows characteristics of 3 female HFpEF phenotypes: phenotype 1 “aging hypertensive”, phenotype 2 “younger hypertensive”, and phenotype 3 “obesity phenotype”. 887 female patients from the TOPCAT trial were analyzed according to these phenotypes. Of these, only phenotype 1 showed a benefit of spironolactone therapy compared to placebo with regards to the primary outcome of CV mortality and HF hospitalizations (20.8% vs 30.2%, p<0.05) as well as the composite of all-cause mortality and CV hospitalizations (41.1% vs 51.3%, p<0.05).
Conclusion:
Older, hypertensive women with HFpEF show a significant reduction in CV mortality and HF hospitalizations when treated with spironolactone vs. placebo, whereas other women did not. Prior studies show that this phenotype is often associated with a higher mortality, thus spironolactone may be particularly important in this patient population.
Serum potassium and outcomes in heart failure with preserved ejection fraction: a post‐hoc analysis of the
PARAGON‐HF
trial
