In patients with heart failure with reduced ejection fraction (HFrEF), treatment with the selective cardiac myosin-activator omecamtiv mecarbil resulted in a lower risk of a composite of heart failure and cardiovascular events, according to results from the placebo-controlled GALACTIC-HF trial .
Prof. John Teerlink (University of California, San Francisco, USA) presented the results of the GALACTIC-HF (NCT02929329) trial, which were simultaneously published in the New England Journal of Medicine . GALACTIC-HF is the first trial to test the hypothesis that selectively improving cardiac function with omecamtiv mecarbil improves outcomes in patients with HFrEF, meaning a decrease in the risk of cardiovascular death, prevention of clinical heart failure events, and improvement of symptoms. Participants were aged 18–85 years with New York Heart Association class II, III, or IV symptoms of chronic heart failure, left ventricular ejection fraction (LVEF) ≤35%, N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≥400 pg/ml, and BNP ≥125 pg/ml. The primary outcome was cardiovascular death or a first heart failure event. Median age was 65 years, 79% of patients were male, and median follow-up was 21.8 months. Comorbidities were highly prevalent: 61% had coronary artery disease, 70% hypertension, 55% hypercholesterolaemia, and 40% type 2 diabetes.
Of the 8,256 participants with HFrEF, 4,120 were randomised to omecamtiv mecarbil and 4,112 to placebo, 24 were excluded because of Good Clinical Practice violations. Based on plasma levels of the drug, patients in the omecamtiv mecarbil group received 25 mg, 37.5 mg, or 50 mg twice daily. The primary outcome occurred in 37.0% of the omecamtiv mecarbil group and in 39.1% of the placebo group (HR 0.92; 95% CI 0.86–0.99; P=0.03). There was possibly a greater treatment effect with omecamtiv mecarbil among patients with LVEF ≤28% (HR 0.84; 95% CI 0.77–0.92). Serious adverse events were similar between treatment groups.
There was no benefit from omecamtiv mecarbil on any of the secondary outcomes. In the omecamtiv mecarbil and the placebo group, respectively:
- the rates of cardiovascular death were 19.6% versus 19.4% (HR 1.01; 95% CI 0.92–1.11;P=0.86);
- the rates of all-cause death were 25.9% versus 25.9%;
- the rates of first hospitalisation for heart failure were 27.7 versus 28.7 (HR 0.95; 95% CI 0.87–1.03); and
- the change in Kansas City Cardiomyopathy Questionnaire (KCCQ) total symptom score at week 24 was 23.7% and 21.2%.
- Teerlink JR, et al. Omecamtiv Mecarbil in Chronic Heart Failure With Reduced Ejection Fraction: The Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) Trial. LBS.01, AHA Scientific Sessions 2020, 13–17 Nov.
- Teerlink JR, et al. on behalf of the GALACTIC-HF Investigators. N Engl J Med 2021; 384:105-116.
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