Analysis of the PARAGON-HF Study Results Using Win Ratio

Circ Heart Fail. 2024 Sep;17(9):e011860. doi: 10.1161/CIRCHEARTFAILURE.124.011860. Epub 2024 Aug 28.

Abstract

Background: The PARAGON-HF study (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction) investigated the effect of sacubitril-valsartan in heart failure (HF) with preserved ejection fraction. The results, which were analyzed using conventional statistical methods, did not find a significant reduction in the primary composite end point of cardiovascular death and total hospitalization for HF. Recent clinical trials used win ratio statistics that enable the incorporation of multiple outcome aspects into the primary end point and can detect positive outcomes with fewer patients. In this study, we assessed the effect of sacubitril-valsartan on outcomes using the win ratio to analyze results from patients included in the PARAGON-HF study.

Methods: In the PARAGON-HF study, 4822 patients with HF with preserved ejection fraction were randomized either to sacubitril-valsartan or valsartan groups. In the present study, the primary outcome was a hierarchical composite of time to cardiovascular death, total number of hospitalization for HF, time to first hospitalization for HF, time to renal composite outcome, and change in the Kansas City Cardiomyopathy Questionnaire total symptom score at 8 months analyzed using a win ratio statistical model.

Results: Using this approach, we found that a greater number of patients who received sacubitril-valsartan experienced clinical benefits compared with those who received valsartan (win ratio, 1.13 [95% CI, 1.04-1.23]; P=0.005). This clinical advantage was evident in patients regardless of whether the left ventricular ejection fraction was above or below the median, that is, the left ventricular ejection fraction of 57%, and regardless of sex (Pinteraction=0.76 for the left ventricular ejection fraction and 0.73 for sex).

Conclusions: Employing the innovative win ratio approach, sacubitril-valsartan demonstrated significant clinical benefits among patients with HF with preserved ejection fraction. Notably, this benefit was observed irrespective of left ventricular ejection fraction and sex.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.

Keywords: heart failure; sacubitril and valsartan sodium hydrate drug combination; therapeutics; treatment outcomes.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Aged
  • Aminobutyrates* / therapeutic use
  • Angiotensin Receptor Antagonists* / therapeutic use
  • Biphenyl Compounds* / therapeutic use
  • Drug Combinations*
  • Female
  • Heart Failure* / drug therapy
  • Heart Failure* / mortality
  • Heart Failure* / physiopathology
  • Hospitalization / statistics & numerical data
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Stroke Volume* / physiology
  • Tetrazoles / therapeutic use
  • Time Factors
  • Treatment Outcome
  • Valsartan* / therapeutic use
  • Ventricular Function, Left / drug effects
  • Ventricular Function, Left / physiology

Substances

  • Valsartan
  • Aminobutyrates
  • sacubitril and valsartan sodium hydrate drug combination
  • Biphenyl Compounds
  • Drug Combinations
  • Angiotensin Receptor Antagonists
  • Tetrazoles

Associated data

  • ClinicalTrials.gov/NCT01920711