Omecamtiv Mecarbil Declines To Improve Exercise Capacity in Patients with HFrEF

Gregory D. Lewis, MD

New research found that omecamtiv mecarbil did not improve exercise capacity over 20 weeks in well-treated patients with chronic heart failure with reduced ejection fraction (HFrEF).

Data show safety signals were similar to placebo without signals related to peak exercise, which was considered consistent with previous studies of the agent.

Led by primary investigator Gregory D. Lewis, MD, Massachusetts General Hospital, these findings were presented at The American College of Cardiology (ACC) 2022 Scientific Sessions in Washington, DC.

Although exercise intolerance is a manifestation of heart failure, current medical therapies have not shown improvement. As a result, the METEORIC-HF study was designed to test the hypothesis that omecamtiv mecarbil can improve exercise capacity in patients with HFrEF.

A randomized, placebo-controlled, double-blind multicenter center evaluated exercise capacity in this patient population receiving maximally tolerated guideline-directed medical therapy. Patients were randomized 2:1 to receive either omecamtiv mecarbil or placebo, while the primary endpoint was the change in peak oxygen uptake (pVO2) from baseline to week 20.

Key inclusion criteria included age ≥18 years to ≤85 years, chronic NYHA class II - III heart failure, LVEF ≤35% within 12 months, NT-proBNP ≥200pg/mL, pVO2 ≤75% of age-predicted normal value on screening CPET, and RER ≥1.05 on screening CPET.

A total of 276 patients were randomized to omecamtiv mecarbil (n = 185) or placebo (n = 91). Patients had a mean age of 64 years, were 89% White (n = 245), and 15% women (n = 42).

Data show a mean baseline peak VO2 score of 14.7 ml/min/kg. At week 20, the mean peak VO2 score was 14.8 ml/min/kg in the omecamtiv mecarbil and 14.9 ml/min/kg for placebo.

For the primary endpoint, a LSM score of -0.24 for omecamtiv mecarbil and 0.21 for placebo, for a difference of -0.45 (95% CI, -1.0 - 0.13; P = .13).

Investigators noted no difference between study groups regarding this primary endpoint, as well as no difference regarding any secondary outcomes, including day-to-day physical activity or perceived functional capacity after taking omecamtiv mecarbil.

In an accompanying press release, Lewis noted that most patients in the trial had experienced symptomatic heart failure for a long time prior to enrollment.

“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.”

The study, “The Effect Of Omecamtiv Mecarbil On Exercise Tolerance In Patients With Chronic Heart Failure And Reduced Ejection Fraction: METEORIC-HF,” was presented at ACC 2022.