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

Autor: Shoji S; Duke Clinical Research Institute, Durham, North Carolina, USA; Department of Cardiology, Keio University School of Medicine, Tokyo, Japan. Electronic address: satoshi.shoji@duke.edu., Cyr DD; Duke Clinical Research Institute, Durham, North Carolina, USA., Hernandez AF; Duke Clinical Research Institute, Durham, North Carolina, USA., Velazquez EJ; Yale School of Medicine, New Haven, USA., Ward JH; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA., Williamson KM; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA., Sarwat S; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA., Starling RC; Cleveland Clinic, Department of Cardiovascular Medicine, Cleveland, USA., Desai AS; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Zieroth S; Section of Cardiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada., Solomon SD; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Mentz RJ; Duke Clinical Research Institute, Durham, North Carolina, USA.
Jazyk: angličtina
Zdroj: American heart journal [Am Heart J] 2024 Nov 04. Date of Electronic Publication: 2024 Nov 04.
DOI: 10.1016/j.ahj.2024.10.020
Abstrakt: 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 pre-specified 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).
Competing Interests: Declaration of competing interest None
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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