For a study, researchers sought to evaluate the ability of omecamtiv mecarbil, a new direct myosin activator that enhances cardiac function and lowers the risk of cardiovascular mortality or the first HF event in heart failure with reduced ejection fraction (HFrEF), to increase peak exercise capacity in people with chronic HFrEF.

Patients with HFrEF (left ventricular ejection fraction ≤35%), symptoms class II–III according to the New York Heart Association, an N-terminal pro-B-type natriuretic peptide level of 200 pg/mL or higher, and a baseline peak oxygen uptake (Vo2) of less than or equal to 75% of predicted are included in this phase 3 double-blind, placebo-controlled trial. At 63 locations across North America and Europe, patients were randomized in a 2:1 ratio (omecamtiv mecarbil vs. placebo) between March 2019 and May 2021, with the final patient visit taking place on November 29, 2021. Omecamtiv mecarbil (n=185) or a matched placebo (n=91) were administered orally twice daily for 20 weeks at doses of 25, 37, or 50 mg, depending on the desired plasma levels. Changes in exercise capacity (peak Vo2) between baseline and week 20 served as the study’s primary endpoint. Total workload, ventilatory effectiveness, and daily physical activity as measured by accelerometry were considered secondary endpoints.

In the study, 249 (90%) of the 276 patients who were randomly assigned (median age, 64 years; interquartile range, 55–70 years; 42 women, 15%) finished it. The median left ventricular ejection fraction was 28% (IQR, 21-33), and the median baseline peak Vo2 was 14.2 mL/kg/min in the omecamtiv mecarbil group and 15.0 mL/kg/min (IQR, 12.0-17.2) in the placebo group. The mean difference in peak Vo2 between the omecamtiv mecarbil and placebo groups was not significant (mean, -0.24 mL/kg/min versus 0.21 mL/kg/min; least square mean difference, -0.45 mL/kg/min [95% CI, -1.02 to 0.13]; P=.13). Adverse events included dizziness (4.9% vs. 5.5% for placebo), fatigue (4.9% vs. 4.4% for placebo), heart failure events (4.9% vs. 4.4% for placebo), death (1.6% vs. 1.1% for placebo), stroke (0.5% vs. 1.1% for placebo), and myocardial infarction (0.5% vs. 1.1% for placebo), and myocardial infraction (omecamtiv mecarbil: 0% , placebo: 1.1%).

Omecamtiv mecarbil did not substantially enhance exercise capacity in patients with chronic HFrEF over 20 weeks as compared to placebo. The results did not support the use of omecamtiv mecarbil for the treatment of HFrEF in order to increase exercise capacity.

Reference: jamanetwork.com/journals/jama/article-abstract/2794362