Satoshi Shoji, Derek D Cyr, Adrian F Hernandez, Eric J Velazquez, Jonathan H Ward, Kristin M Williamson, Samiha Sarwat, Randall C Starling, Akshay S Desai, Shelley Zieroth, Scott D Solomon, Robert J Mentz
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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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Trial registration: </strong>PARAGLIDE-HF; ClinicalTrials.gov ID, NCT03988634 (https://clinicaltrials.gov/study/NCT03988634).</p>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":" ","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Win Ratio Analyses Using a Modified Hierarchical Composite Outcome: Insights from PARAGLIDE-HF.\",\"authors\":\"Satoshi Shoji, Derek D Cyr, Adrian F Hernandez, Eric J Velazquez, Jonathan H Ward, Kristin M Williamson, Samiha Sarwat, Randall C Starling, Akshay S Desai, Shelley Zieroth, Scott D Solomon, Robert J Mentz\",\"doi\":\"10.1016/j.ahj.2024.10.020\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>Multiple WR sensitivity analyses support a consistent treatment benefit of sacubitril/valsartan versus valsartan in patients with ejection fraction >40% to 60%. 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Win Ratio Analyses Using a Modified Hierarchical Composite Outcome: Insights from PARAGLIDE-HF.
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.
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The American Heart Journal will consider for publication suitable articles on topics pertaining to the broad discipline of cardiovascular disease. Our goal is to provide the reader primary investigation, scholarly review, and opinion concerning the practice of cardiovascular medicine. We especially encourage submission of 3 types of reports that are not frequently seen in cardiovascular journals: negative clinical studies, reports on study designs, and studies involving the organization of medical care. The Journal does not accept individual case reports or original articles involving bench laboratory or animal research.
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