Ivabradine significantly improved the hierarchical endpoint of cardiovascular death and heart failure hospitalizations compared to placebo in HFrEF patients (WR 1.23; 95% CI 1.10-1.37; p<0.001).
RCT (n=6,505)
Does ivabradine improve the hierarchical composite of cardiovascular death and heart failure hospitalizations in patients with HFrEF (LVEF ≤35%) and resting heart rate ≥70 bpm?
Win-ratio analysis confirms the clinical benefit of ivabradine over placebo in reducing cardiovascular death and heart failure hospitalizations in patients with HFrEF.
Effect estimate: WR 1.23 (95% CI 1.10-1.37)
p-value: p=<0.001
Abstract Aim To understand how the win-ratio (WR) compares to conventional time-to-first-event and total events analyses, we conducted this study to evaluate WR alongside hazard ratios (HRs) within the SHIFT trial. Methods The SHIFT trial enrolled 6,505 patients with left ventricular ejection fraction (LVEF) ≤35% and a resting heart rate ≥70 beats per minute. Patients were randomized to receive ivabradine or placebo in addition to guideline-based standard care. In the present anaylsis, the clinical benefit was assessed using the WR with a hierarchical endpoint of CV death and number of HFH. This produced one risk score per patient. There were 3,241 patients on ivabradine and 3,264 on placebo, so we removed 23 from the placebo group to equalize the groups. Results Ivabradine showed a statistically significant benefit over placebo for the primary endpoint, with a WR of 1.23 (95% CI: 1.10–1.37; p 0.001), consistent across both CV deaths (53.47% vs. 46.53%, p 0.05) and number of HFH (56.97% vs. 43.03%, p 0.001) (figure 1). No difference was observed between the matched and unmatched analyses, with win ratios of 1.23 (95% CI: 1.11–1.37; p 0.001) and 1.22 (95% CI: 1.11–1.35; p 0.001), respectively. Conclusion These analyses offered a detailed set of win statistics, showcasing their flexibility in evaluating treatment effects. Ivabradine consistently showed clinical benefits across various statistical methods. With recent advancements in win statistics and visualization tools, these approaches provide an alternative to traditional clinical trial analysis methods.
Abdin et al. (Sat,) conducted a rct in HFrEF (n=6,505). Ivabradine vs. Placebo was evaluated on Hierarchical endpoint of CV death and number of HFH (WR 1.23, 95% CI 1.10-1.37, p=<0.001). Ivabradine significantly improved the hierarchical endpoint of cardiovascular death and heart failure hospitalizations compared to placebo in HFrEF patients (WR 1.23; 95% CI 1.10-1.37; p<0.001).