Cardiac contractility modulation significantly improved a hierarchical composite of clinical and functional outcomes compared to OMT in HFrEF patients (win ratio 2.48; 95% CI 1.76-3.64; p<0.001).
RCT (n=160)
Yes
Does cardiac contractility modulation (CCM) therapy improve a hierarchical composite of cardiovascular mortality, heart failure hospitalization, and patient-centered outcomes in patients with HFrEF compared to optimal medical therapy?
A win-ratio re-analysis of the FIX-HF-5C trial demonstrates that cardiac contractility modulation provides comprehensive clinical benefit over optimal medical therapy in HFrEF patients, driven by both clinical events and patient-centered outcomes.
Effect estimate: Win ratio 2.48 (95% CI 1.76-3.64)
p-value: p=< 0.001
BACKGROUND: FIX-HF-5C multicenter, randomized study demonstrated cardiac contractility modulation (CCMTM) improved patient-centered outcomes, including functional capacity, symptom burden, and health-related quality of life. Reductions in cardiovascular death and heart failure hospitalization (HFH) were observed. These event-driven outcomes were not prespecified efficacy endpoints and were not incorporated into overall assessment of treatment benefit. Comprehensive clinical benefit of CCM therapy was re-analyzed by a win-ratio method that integrated event-driven clinical endpoints with patient-centered outcomes. METHODS: The hierarchical win-ratio prioritized cardiovascular mortality, HFH, and patient-centered outcomes comprising equally weighted components of peak oxygen consumption, Minnesota Living with Heart Failure Questionnaire score, 6-minute walk distance, and NYHA functional class. Sub-group analyses were performed in patients with NYHA Class III versus IV. RESULTS: In the primary analysis of 160 randomized patients (6,364 patient pairs), the overall win ratio was 2.48 (95% CI 1.76 to 3.64; p < 0.001), corresponding to a 71% pairwise comparative probability of clinical benefit with CCM versus OMT. Event-driven clinical endpoints accounted for 22% of total wins while 56.2% came from patient-centric endpoints. CCM consistently outperformed OMT across all hierarchies. Sensitivity analyses yielded similar findings with win ratios favoring CCM (range: 1.52 to 2.42). Treatment effects were consistent across NYHA class III and IV subgroups. CONCLUSIONS: The win-ratio re-analysis supports and extends the original study results demonstrating a consistent clinical benefit of CCM therapy over OMT across a hierarchical framework integrating event-driven clinical endpoints with patient-centered functional outcomes. The findings, while clinically highly encouraging, are hypothesis-generating and warrant validation in future confirmatory study.
Kahwash et al. (Tue,) conducted a rct in Heart Failure with Reduced Ejection Fraction (HFrEF) (n=160). Cardiac contractility modulation (CCM) vs. Optimal medical therapy (OMT) was evaluated on Hierarchical win-ratio prioritizing cardiovascular mortality, heart failure hospitalization, and patient-centered functional outcomes (Win ratio 2.48, 95% CI 1.76-3.64, p=< 0.001). Cardiac contractility modulation significantly improved a hierarchical composite of clinical and functional outcomes compared to OMT in HFrEF patients (win ratio 2.48; 95% CI 1.76-3.64; p<0.001).