The novel selective cardiac myosin activator omecamtiv mecarbil produced a greater reduction in heart failure (HF) events in at-risk patients with lower baseline ejection fractions (EF), according to results of a new analysis from the GALACTIC-HF trial presented May 17 during ACC.21 and simultaneously published in the Journal of the American College of Cardiology.

The primary results from GALACTIC-HF showed that in 8,256 patients with HF and reduced EF (<35%) (HFrEF), omecamtiv mecarbil (25 mg, 37.5 mg or 50 mg twice daily) vs. placebo in addition to guideline-directed medical therapy reduced the primary composite endpoint of time to first HF event or cardiovascular death (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.86-0.99; p=0.025). A significant interaction for the effect of the study drug on the primary outcome was seen in patients with an EF ≤28% vs. >28%.

For this prespecified analysis, John R. Teerlink, MD, FACC, et al., examined the effect on the primary outcome of the baseline EF across quartiles (≤22%; 23-28%; 29-32%; ≥33%).

Results showed that EF was the strongest modifier of the effect of omecamtiv mecarbil on the primary outcome (interaction as continuous variable, p=0.004).

As baseline EF decreased, there was a progressively greater relative and absolute treatment effect: in the lowest quartile (n=2,246) there was a 17% relative risk reduction (HR, 0.83; 95% CI, 0.73-0.95) compared with the highest quartile (n=1,750) (HR, 0.99; 95% CI, 0.84-1.16; interaction as EF by quartiles, p=0.013). The absolute risk reduction in the lowest quartile was 7.4 events per 100 patient-years, vs. no reduction in the highest quartile. The number needed to treat for three years was 11.8 in the lowest quartile.

Compared with placebo, with omecamtiv mecarbil there was no significant difference in systolic blood pressure, serum potassium or creatinine. In every quartile, there was a significant, but similar and minimal, reduction in heart rate, and troponin was increased minimally. There was a progressive decrease in NT-proBNP as EF decreased. No differences were seen in serious adverse events or in adjudicated arrhythmic and ischemic events.

"The GALACTIC-HF trial provided the first opportunity to evaluate the effect of improving cardiac function on outcomes in patients with HFrEF. Given its mechanism of action, there is biological plausibility to the hypothesis that patients with greater systolic dysfunction would derive greater benefit," write the investigators.

In a related editorial comment, João Pedro Ferreira, MD, PhD, explains, "In an era where adding more treatments to the therapeutic armamentarium of patients with HFrEF is increasingly difficult, personalized treatment approaches are necessary to cover unmet needs, benefit patients who need the most, and also to be cost-effective and generate return of investment." He adds, that EF and atrial rhythm "are probably the best means to stratify and identify patients responsive to omecamtiv mecarbil in a manner that is completely aligned with the biological mechanisms of the drug and using widely available and inexpensive biomarkers (an echo- and electrocardiogram)."

Clinical Topics: Heart Failure and Cardiomyopathies, Noninvasive Imaging, Acute Heart Failure

Keywords: ACC Annual Scientific Session, ACC21, Heart Failure, Diagnostic Imaging, Stroke Volume, Ventricular Dysfunction, Left

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