Omecamtiv mecarbil fails to improve exercise capacity in HFrEF patients: JAMA

Exercise restriction is a key symptom of heart failure with decreased ejection fraction, however, none of the available medical treatments that follow current guidelines consistently improve this symptom.

According to Gregory D. Lewis, MD, the study's lead researcher, earlier studies on patients with HFrEF showed that omecamtiv mecarbil offered substantial benefits of shortening the time to cardiovascular mortality or the first heart failure event. The researchers also added that there were no signs of any safety concerns at maximum exertion or at any other time during the study and that omecamtiv mecarbil appeared to be well tolerated.

In order to find out if individuals with chronic HFrEF can increase their peak exercise capacity, researchers tested the potential of omecamtiv mecarbil, a novel direct myosin activator that enhances cardiac function and lowers the risk of cardiovascular mortality or the first HF event in HFrEF.

For this purpose, a multicenter, randomized clinical trial with 276 patients with HFrEF was conducted by researchers. At 63 locations across North America and Europe, patients were randomized in a 2:1 ratio between March 2019 and May 2021, with the final patient visit taking place on November 29, 2021. Before the trial and after 20 weeks, researchers evaluated participants' ability to exercise through a range of assessments.

Key findings of the study :

· Among 276 patients who were randomized, 249 (90%) completed the trial.

· The median left ventricular ejection fraction was 28% and the median baseline peak V̇o 2 was 14.2 mL/kg/min in the omecamtiv mecarbil group and 15.0 mL/kg/min in the placebo group.

· Mean change in peak V̇o 2 did not differ significantly between the omecamtiv mecarbil and placebo groups (mean, −0.24 mL/kg/min vs 0.21 mL/kg/min).

· Adverse events included dizziness (omecamtiv mecarbil: 4.9%, placebo:5.5%), fatigue (omecamtiv mecarbil: 4.9%, placebo: 4.4%), heart failure events (omecamtiv mecarbil: 4.9%, placebo: 4.4%), death (omecamtiv mecarbil: 1.6%, placebo: 1.1%), stroke (omecamtiv mecarbil: 0.5%, placebo: 1.1%), and myocardial infarction (omecamtiv mecarbil: 0%, placebo: 1.1%).

The researchers conclude that the medication may not help patients deal with the functional limitations that are a defining feature of the disease.

"Our findings do not support omecamtiv mecarbil use for the treatment of HFrEF for improvement of exercise capacity," the researchers wrote in their study.