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Cilostazol in patients with heart failure and preserved ejection fraction-The CLIP-HFpEF trial

Norman Aiad1,2, Jeanne du Fay de Lavallaz3, Michael J Zhang1,2

  • 1Department of Medicine, Cardiology, University of Minnesota, Minneapolis, Minnesota, USA.

ESC Heart Failure
|November 18, 2024
PubMed

Insights

Cilostazol improved health status and reduced NT-proBNP in heart failure with preserved ejection fraction (HFpEF) patients. This PDE-3 inhibitor may lower cardiac filling pressures by increasing heart rate.

Area of Science:

  • Cardiology
  • Pharmacology
  • Clinical Trials

Background:

  • Patients with heart failure with preserved ejection fraction (HFpEF) often exhibit low resting and exercise heart rates.
  • Phosphodiesterase-3 (PDE-3) inhibitors have demonstrated potential in improving heart rates, hemodynamics, and symptoms in HFpEF.
  • Cilostazol, an oral PDE-3 inhibitor, is currently used for peripheral artery disease.

Purpose of the Study:

  • To evaluate the short-term effects of cilostazol on health status in patients with HFpEF.
  • To assess the impact of cilostazol on N-terminal brain natriuretic peptide (NT-proBNP) levels.
  • To explore the mechanisms of action of cilostazol in this patient population.

Main Methods:

  • A randomized, placebo-controlled, multiple crossover trial (CLIP-HFpEF) involving 23 HFpEF patients.
  • Participants received either placebo or cilostazol for one week, with subsequent crossovers.
  • Primary endpoint: Kansas City Cardiomyopathy Questionnaire (KCCQ-12) overall summary score. Secondary endpoint: NT-proBNP levels. Exploratory analysis of pulmonary artery pressures and heart rates in five patients with implanted monitors.

Main Results:

  • Cilostazol significantly improved the KCCQ score by 4.8 points (P=0.003).
  • NT-proBNP levels decreased on cilostazol (375 pg/mL) compared to placebo (448 pg/mL) (P=0.006).
  • In patients with pressure monitors, cilostazol reduced diastolic pulmonary artery pressure (18.0 mmHg vs 20.5 mmHg), associated with increased heart rates (P<0.001).

Conclusions:

  • Short-term cilostazol treatment improves health status and lowers NT-proBNP in HFpEF patients compared to placebo.
  • The observed benefits are likely mediated by a heart rate-dependent reduction in cardiac filling pressures.
  • Cilostazol demonstrates potential as a therapeutic agent for managing HFpEF.
Abstract

Keywords:
diastolic functionheart failurepharmacotherapypreserved ejection fraction

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