GALACTIC-HF: zooming in on efficacy data and subgroups

Omecamtiv mecarbil reduced the composite of heart-failure event or death from cardiovascular causes compared to placebo among patients with heart failure (HF) in an exploratory analysis of the GALACTIC-HF trial. The analysis examined a hierarchical outcome including clinical, patient-reported, and biomarker measures. Patients with a lower left ventricular ejection fraction (LVEF) and patients with sinus rhythm appeared to benefit more from the agent than others.

The cardiac myosin activator omecamtiv mecarbil reduced the risk of time to first worsening HF event or cardiovascular death among patients with HFrEF in the GALACTIC-HF study [1]. The trial had randomised 8,256 patients 1:1 to omecamtiv mecarbil or placebo. Dr Kieran Docherty (University of Glasgow, UK) and colleagues explored the effect of this drug using a 5-tier hierarchical win ratio method; the 5 tiers being cardiovascular death, number of worsening HF events, a 5-point (outpatients) or 20-point improvement in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) at week 24, a 25% decrease in NT-proBNP, and the relative change in NT-proBNP [2].

There was no difference in win ratio between omecamtiv mecarbil and placebo for cardiovascular death (HR 1.01; 95% CI 0.92–1.11). On the other hand, there was an advantage for the total number of worsening HF events (RR 0.90; 95% CI 0.81–0.99). Next, there was no difference between the study arms regarding 5-point improvement in KCCQ-TSS among outpatients (OR 1.02; 95% CI 0.90–1.15), but there was a difference for the 20-point improvement measure among inpatients in favour of omecamtiv mecarbil (OR 1.35; 95% CI 1.07–1.71). Finally, a reduction of at least 25% in NT-proBNP was more frequently observed in participants in the intervention group (OR 1.25; 95% CI 1.14–1.37). “The overall win ratio was 1.07 (95% CI 1.01–1.13) and the net benefit was 3.3% (95% CI 0.6–6.0),” added Dr Docherty. A subgroup analysis displayed that omecamtiv mecarbil may be more beneficial for patients with an LVEF ≤28% (win ratio 1.16) than for those with an LVEF >28% (win ratio 0.97; P_interaction=0.001). Similarly, the win ratio of omecamtiv mecarbil was higher in patients with sinus rhythm at baseline than in patients with atrial fibrillation or flutter at baseline (1.13 vs 0.91; P_interaction<0.001).

“This data supports ongoing research with omecamtiv mecarbil in the COMET-HF trial (NT06736574), which is recruiting patients with the characteristics that were associated with the largest benefits in GALACTIC-HF,” concluded Dr Docherty.

1. Teerlink JR, et al. N Engl J Med 2021;384(2):105-116.
2. Docherty KF, et al. The effect of omecamtiv mecarbil on outcomes analysed using the win ratio: an exploratory analysis of GALACTIC-HF. Clinical trials updates in medical therapy, Heart Failure 2025, 17–20 May, Belgrade, Serbia.

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Posted on 17 July 202521 July 2025