Omecamtiv mecarbil boosts heart’s pumping action in COSMIC-HF

The novel selective cardiac myosin activator omecamtiv mecarbil improves diastolic function and pulmonary pressures without adversely affecting diastolic filling in patients with chronic heart failure (HF) and reduced systolic function,  the COSMIC-HF* trial has shown.

“Omecamtiv mecarbil increases the entry rate of myosin into the tightly bound force-producing state of actin,” said Associate Professor Tor Biering-Sørensen from the University of Copenhagen in Copenhagen, Denmark, during his presentation of the study findings. [AHA 2019, abstract RF299]

“The making of this action is to increase the duration of systole, thereby, increasing stroke volume. It doesn’t increase the calcium level of the myocytes and it doesn’t change the dP/dt(max) nor does it increase the oxygen consumption,” he continued.

There were nonsignificant decreases in E/A ratio and E-wave in patients assigned a fixed dose (p= 0.3471; p=0.2662, respectively) or those titrated on omecamtiv mecarbil (p=0.0782; p=0.0646, respectively), both of which were dose dependent. Fixed and titrated doses of omecamtiv mecarbil did not affect early peak myocardial relaxation velocity (p=0.7279;p=0.1479, respectively) or E/e’ (p =0.1355; p=0.6718, respectively).

Isovolumic relaxation time slightly increased in patients assigned omecamtiv mecarbil (p for both < 0.0001). The selective cardiac myosin activator decreased tricuspid regurgitant velocity both in the fixed (p=0.9767) and titrated doses (p=0.0055). Of note, the therapy had no effect on the diastolic filling duration.

“Simply put, in addition to increasing  the pumping action of  the heart, omecamtiv  mecarbil did  not change  and, for  some measures, was consistent with improvement of the heart’s diastolic function, or ability to relax between heartbeats,” said Biering-Sørensen.

The phase III GALACTIC-HF** trial, which is currently ongoing, will determine omecamtiv mecarbil’s impact on cardiovascular outcomes, he added.

In the COSMIC-HF trial, data from 448 patients (mean age 63 years, 82 percent male) with stable, symptomatic HF and a left ventricular ejection fraction <40 percent, were analysed. Patients were assigned oral omecamtiv mecarbil 25 mg twice daily (n=150), oral omecamtiv mecarbil 25 mg twice daily uptitrated to 50 mg twice daily (n=149), or placebo (n=149).

Late peak mitral inflow velocities, diastolic filling, and function were assessed using echocardiography, as well as the isovolumic relaxation time, early peak myocardial relaxation velocity, tricuspid regurgitation velocity, and diastolic filling time.

Of the total study population,  82 percent had signs of increased filling pressure based on existing diastolic grading guidelines.

Dr John Teerlink, executive committee chair for the COSMIC-HF and GALACTIC-HF trials and professor of clinical medicine at University of California, San Francisco, California US and director of heart failure at San Francisco Veterans Affairs Medical Center, also in California, US,  commented: “Today, half of heart failure patients will die within 5 years of diagnosis, underscoring an urgent need for new therapies that address a central driver of this condition which is to increase the pumping action of the heart without adversely affecting how the heart fills.”