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Win Ratio Analyses Using a Modified Hierarchical Composite Outcome: Insights From PARAGLIDE-HF.

Publication ,  Journal Article
Shoji, S; Cyr, DD; Hernandez, AF; Velazquez, EJ; Ward, JH; Williamson, KM; Sarwat, S; Starling, RC; Desai, AS; Zieroth, S; Solomon, SD; Mentz, RJ
Published in: Am Heart J
February 2025

BACKGROUND: The win ratio (WR) is an emerging alternative for reporting composite outcomes, prioritizing clinically significant events such as mortality while incorporating surrogate measures. However, its benefits should be weighed against limitations, particularly the influence of lower hierarchical outcomes. This secondary analysis of the PARAGLIDE-HF trial performed a WR sensitivity analysis using a modified hierarchical composite outcome to assess the utility of WR sensitivity analysis and the efficacy of sacubitril/valsartan versus valsartan. METHODS: PARAGLIDE-HF compared sacubitril/valsartan with valsartan in heart failure (HF) patients with ejection fraction >40% (N = 466). A hierarchical outcome in the primary analysis included cardiovascular death, HF hospitalizations, urgent HF visits, and change in N-terminal pro-B-type natriuretic peptide (NT-proBNP), with a 25% decrease considered a win. In the prespecified subgroup with ejection fraction ≤60% (N = 357), sacubitril/valsartan showed a treatment effect on the hierarchical outcome (WR, 1.46; 95% CI, 1.08-1.97). Sensitivity analyses for this subgroup included: (1) excluding NT-proBNP change, (2) substituting the 25% proportion change of NT-proBNP with 10% or 50%, and (3) including renal outcomes within the hierarchical outcome. In addition to the WR, the win odds (WO), in which 50% of the ties are allocated to both the numerator and denominator of the WR-a potentially more suitable modification of the WR that accounts for the presence of ties-were presented. RESULTS: Excluding NT-proBNP (WR, 1.49; 95% CI, 1.00-2.22; WO, 1.12; 95% CI, 1.00-1.26), adjusting the NT-proBNP threshold from 25% to 10% or 50% (WR, 1.41; 95% CI, 1.06-1.89; WO, 1.27; 95% CI, 1.04-1.56 for 10%; and WR, 1.54; 95% CI, 1.11-2.12; WO, 1.25; 95% CI, 1.06-1.48 for 50%), and incorporating renal outcomes (WR, 1.44; 95% CI, 1.07-1.94; WO, 1.28; 95% CI, 1.05-1.56) consistently favored sacubitril/valsartan. CONCLUSIONS: Multiple WR sensitivity analyses support a consistent treatment benefit of sacubitril/valsartan versus valsartan in patients with ejection fraction >40% to 60%. Future studies could consider prespecifying WR sensitivity analysis for comprehensive assessment of treatment effects. TRIAL REGISTRATION: PARAGLIDE-HF; ClinicalTrials.gov ID, NCT03988634 (https://clinicaltrials.gov/study/NCT03988634).

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Published In

Am Heart J

DOI

EISSN

1097-6744

Publication Date

February 2025

Volume

280

Start / End Page

70 / 78

Location

United States

Related Subject Headings

  • Valsartan
  • Treatment Outcome
  • Tetrazoles
  • Stroke Volume
  • Peptide Fragments
  • Natriuretic Peptide, Brain
  • Middle Aged
  • Male
  • Humans
  • Hospitalization
 

Citation

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Shoji, S., Cyr, D. D., Hernandez, A. F., Velazquez, E. J., Ward, J. H., Williamson, K. M., … Mentz, R. J. (2025). Win Ratio Analyses Using a Modified Hierarchical Composite Outcome: Insights From PARAGLIDE-HF. Am Heart J, 280, 70–78. https://doi.org/10.1016/j.ahj.2024.10.020
Shoji, Satoshi, Derek D. Cyr, Adrian F. Hernandez, Eric J. Velazquez, Jonathan H. Ward, Kristin M. Williamson, Samiha Sarwat, et al. “Win Ratio Analyses Using a Modified Hierarchical Composite Outcome: Insights From PARAGLIDE-HF.Am Heart J 280 (February 2025): 70–78. https://doi.org/10.1016/j.ahj.2024.10.020.
Shoji S, Cyr DD, Hernandez AF, Velazquez EJ, Ward JH, Williamson KM, et al. Win Ratio Analyses Using a Modified Hierarchical Composite Outcome: Insights From PARAGLIDE-HF. Am Heart J. 2025 Feb;280:70–8.
Shoji, Satoshi, et al. “Win Ratio Analyses Using a Modified Hierarchical Composite Outcome: Insights From PARAGLIDE-HF.Am Heart J, vol. 280, Feb. 2025, pp. 70–78. Pubmed, doi:10.1016/j.ahj.2024.10.020.
Shoji S, Cyr DD, Hernandez AF, Velazquez EJ, Ward JH, Williamson KM, Sarwat S, Starling RC, Desai AS, Zieroth S, Solomon SD, Mentz RJ. Win Ratio Analyses Using a Modified Hierarchical Composite Outcome: Insights From PARAGLIDE-HF. Am Heart J. 2025 Feb;280:70–78.
Journal cover image

Published In

Am Heart J

DOI

EISSN

1097-6744

Publication Date

February 2025

Volume

280

Start / End Page

70 / 78

Location

United States

Related Subject Headings

  • Valsartan
  • Treatment Outcome
  • Tetrazoles
  • Stroke Volume
  • Peptide Fragments
  • Natriuretic Peptide, Brain
  • Middle Aged
  • Male
  • Humans
  • Hospitalization