COSMIC-HF: Omecamtiv mecarbil shows promise for favorable ventricular remodeling

Omecamtiv mecarbil was associated with improvements in various parameters that could lead to favorable ventricular remodeling and reduced myocardial wall stress in patients with HF, according to new data from the COSMIC-HF study.

Researchers evaluated whether increasing contractility with omecamtiv mecarbil (Amgen/Cytokinetics), a novel selective cardiac myosin activator, would affect cardiac volume and function metrics in patients with HF. They presented their findings at Heart Failure 2016 and the 3rd World Congress on Acute Heart Failure in Florence, Italy.

For the phase 2b COSMIC-HF study, John R. Teerlink, MD, and colleagues randomly assigned 448 patients with HF with reduced ejection fraction (mean age, 63 years; 82% men) to omecamtiv mecarbil 25 mg twice daily, omecamtiv mecarbil 25 mg twice daily with uptitration to 50 mg twice daily based on pharmacokinetics (PK titration group) or placebo.

John R. Teerlink

Outcomes of interest included changes in systolic ejection time, stroke volume, LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV), heart rate and N-terminal pro–B-type natriuretic peptide. Follow-up was 20 weeks, with measurements also taken at 12 weeks.

Teerlink, from the San Francisco Veterans Affairs Medical Center and the University of California, San Francisco, and colleagues found that compared with the placebo group, the PK titration group had increased systolic ejection time at 12 and 20 weeks (P < .0001 for both), had greater increase in stroke volume at 12 (P = .038) and 20 weeks (P = .022) and had greater decline in LVESV at 12 (P = .009) and 20 weeks (P = .005). For those metrics, levels of change in the PK titration group were similar at 12 and 20 weeks, according to the researchers.

However, Teerlink and colleagues observed a progressive decline in LVEDV in the PK titration group compared with the placebo group (P at 12 weeks = .17; P at 20 weeks = .021) and a progressive decline in NT-proBNP (P vs. placebo at 12 weeks = .087; P vs. placebo at 20 weeks = .007). The decline in NT-proBNP continued at 24 weeks despite the study drug being discontinued (P < .001).

Heart rate fell approximately 4 bpm in the PK titration group at 12 weeks (P vs. placebo < .0001); the decline was approximately 3 bpm at 20 weeks (P vs. placebo = .007).

At 12 weeks, LVEF improved nearly 3% in the PK titration group (P vs. placebo = .0002), but at 20 weeks, the improvement declined to approximately 1.5% (P vs. placebo = .063), according to the researchers.

“Decreases in diastolic volume and in NT-proBNP during treatment accumulated over time and suggest favorable ventricular remodeling and a progressive reduction in myocardial wall stress,” Teerlink and colleagues wrote in an abstract. “The magnitude of cardiac effects observed in this trial may potentially translate to improvements in clinical outcomes.” – by Erik Swain

Reference:

Teerlink JR, et al. Abstract P2206. Presented at: Heart Failure 2016 and the 3rd World Congress on Acute Heart Failure; May 21-24, 2016; Florence, Italy.

Disclosure : The study was funded by Amgen and Cytokinetics. Teerlink reports receiving research grants from Amgen, Bayer, Cytokinetics, Masi Therapeutics, Novartis and Trevena, and consulting for Amgen, Cytokinetics, Masi Therapeutics, Novartis and Trevena.

Editor's Note: This article was modified on June 3, 2016 to correct an error in the data. The editors regret the error.