PHILADELPHIA — Omecamtiv mecarbil, a selective cardiac myosin activator, improved diastolic function and pulmonary pressures without worsening diastolic filling in patients with chronic HF and reduced systolic function, according to data presented at the American Heart Association Scientific Sessions.
Researchers analyzed data from 448 patients (mean age, 63 years; 82% men) with stable, symptomatic HF and a left ventricular ejection fraction less than 40%. Patients were assigned oral omecamtiv mecarbil (Amgen/Cytokinetics) 25 mg twice per day (n = 150), oral omecamtiv mecarbil 25 mg twice per day uptitrated to 50 mg twice per day (n = 149) or placebo (n = 149).
“[Omecamtiv mecarbil] is a novel selective cardiac myosin activator that increases the entry rate of myosin into the tightly bound force-producing state of actin,” Tor Biering-Sørensen, MD, PhD, MPH, associate professor and research director in the department of biomedical sciences at the University of Copenhagen in Denmark, said during the presentation. “The making of this action is to increase the duration of systole and, 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.”
Echocardiography was performed to assess late peak mitral inflow velocities, diastolic and filling and function, isovolumic relaxation time, early peak myocardial relaxation velocity, tricuspid regurgitation velocity and diastolic filling time.
Of the patients in the study, 82% had signs of increased filling pressure based on current diastolic grading guidelines.
There were nonsignificant decreases in E/A ratio and E-wave in patients assigned a fixed dose (P = .3471; P = .2662, respectively) or were titrated on omecamtiv mecarbil (P = .0782; P = .0646, respectively), both of which were dose dependent. Fixed and titrated doses of omecamtiv mecarbil did not affect early peak myocardial relaxation velocity (P = .7279; P = .1479, respectively) or E/e’ (P = .1355; P = .6718, respectively).
Isovolumic relaxation time slightly increased in patients assigned omecamtiv mecarbil (P for both < .0001). Omecamtiv mecarbil decreased tricuspid regurgitant velocity in the fixed (P = .9767) and titrated doses (P = .0055). The treatment did not affect diastolic filling time duration.
“The impact of [omecamtiv mecarbil] on cardiovascular outcomes is currently being tested in the phase 3 trial GALACTIC-HF,” Biering-Sørensen said during the presentation.
John Teerlink, MD, professor of clinical medicine at University of California, San Francisco, director of heart failure at San Francisco Veterans Affairs Medical Center and executive committee chair for the COSMIC-HF and GALACTIC-HF trials, commented on the trial in a press release from Amgen, Cytokinetics and Servier: “Today, half of heart failure patients will die within 5 years of diagnosis, underscoring the urgent need for new therapies that address a central driver of this condition: to increase the heart’s pumping action without adversely affecting how the heart fills.” – by Darlene Dobkowski
Biering-Sørensen T, et al. Abstract RF299. Presented at: American Heart Association Scientific Sessions; Nov. 16-18, 2019; Philadelphia.
Disclosures: The trial was sponsored by Amgen. Biering-Sørensen reports no relevant financial disclosures. Teerlink reports he is an executive committee chair for the COSMIC-HF and GALACTIC-HF trials.