The win ratio for evaluating edoxaban versus dalteparin for cancer-associated venous thromboembolism: an analysis of the randomized Hokusai VTE cancer trial.
Academic Article
Overview
abstract
BACKGROUND: The Hokusai VTE Cancer trial demonstrated that edoxaban was noninferior to dalteparin for the treatment of cancer-associated venous thromboembolism (VTE. We re-analyzed the trial using the win-ratio, an approach that evaluates a composite of outcomes in a hierarchical order. METHODS: Forty-nine thrombosis experts ranked 10 outcomes in order of clinical importance from all-cause death (most important) to clinically relevant nonmajor bleeding (least important). We performed unmatched pairwise comparisons between participants on edoxaban and dalteparin over the 6- and 12-month follow-up periods. Within each pair, edoxaban was assigned a win, loss, or tie using the hierarchy of outcomes. We calculated the win-ratio (total wins divided by total losses among edoxaban patients), with more wins than losses indicating the benefit of edoxaban, and the win difference (total wins minus total losses). RESULTS: Among 273,528 pairs (522x524 participants), edoxaban was associated with a win in 34.9%, a loss in 38.5%, and a tie in 26.6%. The win-ratio was 0.91 (95%-CI, 0.76 to 1.08) with a win difference of -3.55% (95%-CI, -9.9 to 2.9) at 12 months. The win-ratio remained unchanged at 6 months (0.91, 95%-CI; 0.75-1.11). Findings were consistent with a hierarchy of only death, recurrent VTE, and major bleeding (win-ratio, 0.92; 95%-CI, 0.76 to 1.11) or when replacing all-cause death with VTE-related death or fatal bleeding (win ratio, 0.83; 95%-CI, 0.65 to 1.06). CONCLUSION: We observed no significant difference between edoxaban and dalteparin for the treatment of cancer-associated VTE when using the win-ratio approach with a hierarchy of 10 prioritized outcomes.
