Patients with heart failure with reduced ejection fraction (HFrEF) did not see an improvement in their ability to do vigorous exercise after taking the investigational drug omecamtiv mecarbil, according to a study presented at the 71st conference of the American College of Cardiology.st Annual scientific session.
Many patients with acute heart failure – a condition in which the heart does not contract as hard as it should, preventing it from meeting the body’s needs – tire easily and become short of breath during physical activity. In previous trials, omecamtiv mecarbil was found to provide significant benefits in terms of reducing the time to cardiovascular death or the first event of heart failure in these patients. However, the new results suggest that the drug does not help overcome the day-to-day functional limitations that are a hallmark of the disease.
When added to excellent background therapy, we saw no significant improvement in exercise capacity. Unfortunately, this is not the first time that there has been a drug that improves results but does not improve exercise capacity. There is a lingering frontier in heart failure to help patients improve their functional ability, and it seems we need to look beyond our current and expanding drug therapy regimen to meet this need. »
Gregory D. Lewis, MD, Heart Failure Section Chief and Medical Director of Heart Transplantation at Massachusetts General Hospital and senior study author.
The trial enrolled 276 patients who were already receiving guideline-directed medical treatment for HFrEF at maximum tolerated doses. Two-thirds of the participants were randomly assigned to receive omecamtiv mecarbil in addition to their normal treatment and one-third received a placebo. The researchers performed a series of tests to assess participants’ exercise capacity before the study and after 20 weeks.
The researchers found no difference between the study groups in the primary endpoint of the trial, which was change in maximal oxygen uptake as measured by a cardiopulmonary exercise test. , the gold standard for assessing exercise capacity. There was also no difference in the study’s secondary endpoints, which included a variety of other tests used to assess lung and heart function during exercise. Participants did not show improvement in daily physical activity, measured by wearable accelerometers, or perceived functional ability after taking omecamtiv mecarbil.
Exercise intolerance is a prominent symptom of heart failure that limits a person’s daily activities. As the heart weakens, other organ systems also deteriorate. Because exercise capacity reflects the performance of multiple organ systems, a measurable improvement in exercise capacity would require a large enough improvement in heart function to compensate for impairments in lung and other organ function, Lewis said. He added that most of the trial participants had suffered from symptomatic heart failure for a long time before enrolling in the study.
“When you have chronic heart failure, there are effects on almost every organ system in the body,” Lewis said. “Perhaps one cardio-specific intervention given over a period of five months is not adequate to reverse and overcome the full influence of heart failure on the whole body and its ability to achieve maximal exercise when heart failure has been present for more than five years. »
The drug was well tolerated, and the researchers found no indication of safety issues, either during maximal exercise or at any other time during the trial. No significant differences were observed between the study subgroups, which Lewis said was expected given the relatively small size of the trial.
The study was funded by Cytokinetics.
Dr. Michael Felker, co-chair of the executive committee for this trial, will be available to the media at a press conference on Sunday, April 3 at 11:15 a.m. ET/3:15 p.m. UTC in room 103AB.
Felker will present “The Effect of Omecamtiv Mecarbil on Exercise Tolerance in Patients with Chronic Heart Failure and Reduced Ejection Fraction: METEORIC-HF” study on Sunday, April 3, at 9:45 a.m. ET / 1:45 p.m. UTC in the main tent, Hall D.
Source :
American College of Cardiology