GALACTIC-HF: Benefit of omecamtiv mecarbil strongest at lowest EF
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The treatment effect of omecamtiv mecarbil in patients with HF rose as left ventricular ejection fraction declined, according to new data from the GALACTIC-HF trial presented at the American College of Cardiology Scientific Session.
As Healio previously reported, in the main results of GALACTIC-HF, for patients with symptomatic chronic HF with EF 35% or less already taking standard HF therapies, omecamtiv mecarbil (Cytokinetics), a novel selective cardiac myosin activator, was superior to placebo for prevention of CV death or first HF event. John R. Teerlink, MD, FACC, FAHA, FESC, FHFA, FHFSA, FRCP, professor of medicine at the University of California, San Francisco, and director of heart failure and the echocardiography laboratory at the San Francisco Veterans Affairs Medical Center, presented a secondary analysis of the treatment effect of omecamtiv mecarbil according to EF.
“Given its mechanism of increasing cardiac function, and based on prespecified subgroup analyses, we assessed the modifying effect of the baseline ejection fraction on the beneficial treatment effect of omecamtiv mecarbil,” Teerlink said during his presentation.
For the analysis, the 8,256 patients were stratified into quartiles based on EF: 33% or greater, 29% to 32%; 23% to 28%, and 22% or less. Compared with patients in the highest quartile, those in the lowest were younger, less likely to be women and less likely to be white, according to the researchers.
The risk for the primary composite endpoint in the placebo group was 1.8-fold higher in the lowest quartile of EF compared with the highest quartile, and the strongest modifier of the treatment effect of omecamtiv mecarbil on the primary endpoint was EF (P for interaction as continuous variable = .004), the researchers found.
In the lowest quartile of EF, omecamtiv mecarbil was associated with a 17% reduced risk for the primary endpoint (HR = 0.83; 95% CI, 0.73-0.95), but in the highest quartile, there was no difference between the omecamtiv mecarbil and placebo groups (HR = 0.99; 95% CI, 0.84-1.16; P for interaction = .013), according to the researchers.
In the lowest quartile, there was an absolute risk reduction of 7.4 events per 100 patient-years (number needed to treat for 3 years to prevent one primary outcome event, 11.8) for those assigned omecamtiv mecarbil, but in the highest quartile, there was no absolute risk reduction, Teerlink and colleagues found.
“The treatment effect of omecamtiv mecarbil increased with decreasing ejection fraction, such that in the lowest quartile, fewer than 12 patients would need to be treated to prevent one heart failure event or cardiovascular death,” Teerlink said during the presentation. “Omecamtiv mecarbil appears to be safe; there were no differences in adverse ischemic or arrhythmic events or serious adverse events across the range of ejection fractions between the omecamtiv mecarbil and placebo groups. Importantly, there was no adverse effect on blood pressure, heart rate, potassium homeostasis or renal function, even in the lowest EF quartile, suggesting that omecamtiv mecarbil can be readily initiated in the context of contemporary guideline-directed medical therapy.”
Reference:
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Mary Norine Walsh, MD, MACC
This secondary analysis of the primary trial analyzed the treatment effect of omecamtiv mecarbil by baseline ejection fraction at study entry. The treatment effect increased with decreasing ejection fraction. This may ultimately be a therapy for our sickest patients with advanced HF who are not candidates for mechanical circulatory support or cardiac transplantation.
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Teerlink JR, et al. Late-Breaking Clinical Trials IV. Presented at: American College of Cardiology Scientific Session; May 15-17, 2021 (virtual meeting).
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