Reviewer: Dr. Meltem Tekin

Name of the study: Multicenter exercise tolerance evaluation of omecamtiv mecarbil related to increased ccontractility in heart failure-METEORIC-HF

Presented congress: ACC 22

Background
Exercise intolerance is an important factor on morbidity in heart failure patients with reduced ejection fraction (HFrEF). A new generation of agents is needed to improve exercise capacity in symptomatic patients despite the guideline derived medical treatment (GDMT).

Objective
METEORIC-HF trial is a placebo controlled study that aimed to evaluate the effect of omecamtiv mecarbil on exercise tolerance in HFrEF patients.

Method
METEORIC-HF was a randomised, double blinded, placebo controlled trial. 276 heart failure patients with left ventricular ejection fraction 35% or less, NYHA class 2-3 symptoms, NT-proBNP level was higher than 200 were included this study. Patients were randomised in 2:1 fashion to omecamtiv mecarbil and placebo arm. Omecamtiv mecarbil was given twice daily in treatment group for 20 weeks. The dosage of drug was determined by periodicly with blood tests.

Results
Primary outcome was change in peak oxygen uptake on cardiopulmonary exercise testing. Secondary outcomes were improvement  in exercise capacity, ventilatory efficiency and the average daily activity. Patients were evaluated at baseline and after 20-week-treatment. There was no difference between two groups in terms of primary and secondary outcomes. In addition, no difference was found in the level of physical ativity or functional capacity of the patients.

Conclusion
Omecamtiv mecarbil is a selective myosine activator. It was not found superior to placebo for peak oxygen uptake, physical activity level or functional capacity in HFrEF patients.

Interpretation
Omecamtiv mecarbil increase cardiac contractility directly. In a phase 3 cardiovascular outcome trial, the composite endpoint of cardiovascular death and time to first heart failure event was decreased in HFrEF patients with omecamtiv mecarbil. However, a randomised, placebo controlled METEORIC-HF trial didn't show anticipated effect on HFrEF patients. However, the anticipated effect on HFrEF patients was not observed in the METEORIC-HF study, a randomized placebo-controlled trial. Despite of GDMT, new agents are needed to improve ongoing symptoms and functional capacity in this population.