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Omecamtiv mecarbil does not impact exercise capacity of patients with HFrEF

Presented By
Prof. Michael Felker, Duke Clinical Research Institute, USA
ACC 2022
The multicentre, randomised, phase 3 METEORIC-HF trial reported that the cardiac myosin activator omecamtiv mecarbil did not improve exercise capacity over 20 weeks in heart failure patients with reduced ejection fraction (HFrEF).

Prof. Michael Felker (Duke Clinical Research Institute, NC, USA) presented the METEORIC-HF results (NCT03759392), which come 18 months after omecamtiv mecarbil showed mixed results in the GALACTIC-HF trial [1,2]. Although GALACTIC-HF did meet its primary objective of reducing cardiovascular death or heart failure events compared with placebo, the top-line mortality data did not support overall clinical benefit [2].

Given the substantial day-to-day functional limitations HFrEF patients experience, METEORIC-HF was designed in the hope that a course of 20 weeks of omecamtiv mecarbil therapy would improve exercise capacity [1]. To this end, the study randomised 276 symptomatic HFrEF patients who were already receiving maximally tolerated doses of guideline-directed medical therapy for HFrEF in a 2:1 ratio to either receive omecamtiv mecarbil or placebo on top of their current regimen, both for a period of 20 weeks.

The trial did not meet its primary endpoint; the change in peak oxygen uptake as measured by cardiopulmonary exercise testing showed a least-squares mean difference of -0.45 (95% CI -1 to 0.13; P=0.13). Likewise, secondary outcomes were also similar between the 2 arms, including changes in peak workload, ventilatory efficiency, ventilatory anaerobic threshold, circulatory power, oxygen uptake kinetics, daily activity by actigraphy, and perceived functional capacity by Kansas City Cardiomyopathy Questionnaire (KCCQ). However, the safety outcomes were positive, with no outstanding signals in either trial arm, even at peak exercise.

“Omecamtiv mecarbil did not improve measures of exercise capacity over a 20-week period,” Prof. Felker said. “Identifying therapies that can safely improve exercise capacity, one of the cardinal symptoms of HF, remains an unmet challenge.”

    1. Felker GM, et al. The Effect Of Omecamtiv Mecarbil On Exercise Tolerance In Patients With Chronic Heart Failure And Reduced Ejection Fraction: METEORIC-HF. Abstract 406–010, ACC 2022, 2–4 April, Washington DC, USA.

    2. Teerlink JR, et al. N Engl J Med 2021;384:105–116.


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