Experimental heart failure drug has little impact on exercise tolerance

Heart failure patients taking the investigational drug omecamtiv mecarbil, which has been previously shown to improve long-term outcomes, see little impact on their ability to exercise compared to a placebo, according to a study supported by the Duke Clinical Research Institute.

The study was designed to test whether the new therapy — a selective cardiac myosin activator — could yield improvements in overall exercise capacity for patients with heart failure. Therapies that help heart failure patients better tolerate exercise remains an unmet need.

The findings were reported April 3 as a late-breaking presentation at the 2022 American College of Cardiology Scientific Sessions. Circulation: Heart Failure published the study design in March 2022.

We are fortunate to have a lot of medications in heart failure that can help patients live longer or stay out of the hospital — all very important goals."

Michael Felker, M.D., study co-chair and a Duke Clinical Research Institute (DCRI) faculty member

"However, exercise tolerance is the main symptom patients with heart failure have," Felker said. "They get tired or out of breath very easily. This is a major impediment for their quality of life. Unfortunately, many of the guideline-directed drugs that improve survival don't improve exercise tolerance."

The research study, called the Multicenter Exercise Tolerance Evaluation of Omecamtiv Mecarbil Related to Increased Contractility in Heart Failure (METEORIC-HF), recruited patients across 64 sites in nine countries. It included 276 adult heart failure patients with reduced ejection fraction; they were randomly assigned to receive the study medication or a placebo. The results were blinded to the investigators, the study sponsor, and the participants.

As its primary outcome, METEORIC-HF sought to examine the changes omecamtiv mecarbil had on peak oxygen uptake during cardiopulmonary exercise over a 20-week period. Secondary outcome measurements included assessing overall exercise capacity, ventilator efficiency, and daily activity.

"We found in the trial that even though omecamtiv mecarbil was safe and well-tolerated, it did not improve exercise tolerance over placebo," Felker said. "I think what that tells us is finding interventions that can improve people's exercise tolerance is still an unsolved/unmet need for our patients with heart failure. What our trial has done is helped better define what this medication does and doesn't do."

During the METEORIC-HF trial, study authors for the Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) trial published their own results. That trial examined outcomes between omecamtiv mecarbil and a placebo in a broad population of over 8,000 symptomatic patients. GALACTIC-HF found that omecamtiv mecarbil decreased the rate of heart failure or death from cardiovascular causes.

Felker and Gregory Lewis, M.D., at Massachusetts General Hospital, co-chaired the study.

In addition to Felker and Lewis, study authors include Kieran Docherty, Adriaan Voors, Alain Cohen-Solal, Marco Metra, David Whellan, Justin Ezekowitz, Piotr Ponikowski, Michael Böhm, John Teerlink, Stephen Heitner, Stuart Kupfer, Fady Malik, and Lisa Meng.