METEORIC-HF: Omecamtiv Mecarbil Fails to Improve Exercise Capacity in HFrEF

Omecamtiv mecarbil does not improve exercise capacity among patients with heart failure with reduced ejection fraction, according to results of the METEORIC-HF study.

Presented at the American College of Cardiology’s 71st Annual Scientific Sessions, results of the study indicate use of the first-in-class cardiac myosin activator failed to improve exercise capacity and did not result in increases in perceived functional ability among patients in the trial.

“When added to excellent background therapy, we found no significant improvement in exercise capacity,” said Gregory D. Lewis, MD, section head of heart failure and medical director of heart transplantation at Massachusetts General Hospital and the study’s lead author, in a statement. “This is unfortunately not the first time that there has been a medication that improves outcomes but doesn’t improve exercise capacity. There is a persistent frontier in heart failure to help patients improve their functional capacity, and it seems like we may need to look beyond our current and expanding pharmacotherapy regimen to address this need.”

A randomized, placebo-controlled, double-blind, multicenter study, METEORIC-HF was designed with the intent of assessing the impact of omecamtiv mecarbil use on exercise capacity in patented with symptomatic HFrEF who are already receiving maximally tolerated GDMT. Patients in the trial were randomized in a 2:1 ratio to receive either omecamtiv mecarbil or placebo therapy for a 20-week treatment period.

For inclusion in the trial, patients needed to be between the ages of 18-85 years, have chronic NYHA class 2-3 heart failure, an LVEF at or above 35% within 12 months, be on maximally tolerated heart failure therapies, have an NT-proBNP level of 200 pg/mL or greater, and a peak VO2 at or below 75% of the age-predicted normal value. In total, 276 patients were randomized in the trial, with 91 randomized to placebo and 185 randomized to omecamtiv mecarbil. The overall study cohort had a median age of 64 (IQR, 56-72) years and 15.2% were female.

The primary outcome of interest for the trial was change in peak oxygen uptake from baseline to week 20, which was measured using cardiopulmonary exercise testing. Secondary outcomes of interest included change in peak workload, ventilatory efficiency, ventilatory anaerobic threshold, circulatory power, oxygen uptake kinetics, daily activity by actigraphy, and perceived functional capacity measured by KCCQ.

Upon analysis, results of the trial indicated use of omecamtiv mecarbil was not associated with a significant difference in exercise capacity at 20 weeks, nor were any significant differences observed for the study’s secondary outcomes of interest. Additionally, investigators pointed out there were no improvements observed for day-to-day physical activity or perceived functional capacity.

In the ACC.22 statement, investigators pointed out there were no indication of safety concerns either during maximum exercise or at any other point in the trial. Additionally, no significant differences were observed among study subgroups.

“When you have chronic heart failure, there are effects on almost every organ system in the body,” Lewis said. “Perhaps a cardio-specific intervention given for a period of five months is not adequate to reverse and overcome the totality of influence of heart failure on the whole body and its ability to perform maximum exercise when heart failure has been present for more than five years.”

This study, “The Effect of Omecamtiv Mecarbil on Exercise Capacity in Chronic Heart Failure with Reduced Ejection Fraction: The METEORIC-HF Study,” was presented at ACC.22.