Designing Future Clinical Trials in Heart Failure With Preserved Ejection Fraction: Lessons From TOPCAT

Ravi B. Patel, Sanjiv J. Shah, Gregg C. Fonarow, Javed Butler, Muthiah Vaduganathan*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

13 Scopus citations


Purpose of Review: Spironolactone did not demonstrate benefit with respect to the primary composite endpoint in the global TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial in patients with chronic heart failure with preserved ejection fraction (HFpEF). We identify key lessons from the TOPCAT experience that can be applied to future HFpEF trials. Recent Findings: Subsequent analyses of TOPCAT have revealed marked regional heterogeneity in patient profiles, event rates, drug adherence, and treatment effects. Significant regional variation may impact the success of global HFpEF trials. Given potential benefits in the Americas subgroup in TOPCAT, mineralocorticoid receptor antagonists can be considered in appropriately selected patients with HFpEF to reduce risk of heart failure hospitalization. A planned registry-based trial should provide additional evidence regarding the role of spironolactone in HFpEF. Summary: The overall design, execution, and study oversight of TOPCAT have provided key insights into the conduct of future HFpEF trials.

Original languageEnglish (US)
Pages (from-to)217-222
Number of pages6
JournalCurrent heart failure reports
Issue number4
StatePublished - Aug 1 2017


  • Clinical trials
  • Heart failure with preserved ejection fraction
  • International variation
  • Mineralocorticoid receptor antagonists
  • Spironolactone
  • Study design

ASJC Scopus subject areas

  • Emergency Medicine
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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