Win Ratio Analyses Using a Modified Hierarchical Composite Outcome: Insights From PARAGLIDE-HF - 08/12/24
, Derek D. Cyr, PhD a, Adrian F. Hernandez, MD, MHS a, Eric J. Velazquez, MD c, Jonathan H. Ward, PharmD d, Kristin M. Williamson, PharmD d, Samiha Sarwat, PhD d, Randall C. Starling, MD, MPH e, Akshay S. Desai, MD, MPH f, Shelley Zieroth, MD g, Scott D. Solomon, MD f, Robert J. Mentz, MD aABSTRACT |
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 (NCT03988634).
Le texte complet de cet article est disponible en PDF.Plan
Vol 280
P. 70-78 - février 2025 Retour au numéro
Article précédent
- Effect of apixaban versus vitamin K antagonist and aspirin versus placebo on days alive and out of hospital: An analysis from AUGUSTUS
- Alexander C. Fanaroff, Amit N. Vora, Daniel M. Wojdyla, Roxana Mehran, Christopher B. Granger, Shaun G. Goodman, Ronald Aronson, Stephan Windecker, John H. Alexander, Renato D. Lopes
- Impact of moderate or severe mitral and tricuspid valves regurgitation after transcatheter aortic valve replacement
- Bishoy Abraham, Mustafa Suppah, Juan Farina, Michael Botros, Ayman Fath, Sara Kaldas, Michael Megaly, Chieh-Ju Chao, Reza Arsanjani, Chadi Ayoub, F. David Fortuin, John Sweeney, Patricia Pellikka, Vuyisile Nkomo, Mohamad Alkhouli, David Holmes, Amr Badr, Said Alsidawi
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?