BACKGROUND: Chronic heart failure with reduced ejection fraction impairs 
health-related quality of life (HRQL). Omecamtiv mecarbil (OM)-a novel activator 
of cardiac myosin-improves left ventricular systolic function and remodeling and 
reduces natriuretic peptides. We sought to evaluate the effect of OM on symptoms 
and HRQL in patients with chronic heart failure with reduced ejection fraction 
and elevated natriuretic peptides enrolled in the COSMIC-HF trial (Chronic Oral 
Study of Myosin Activation to Increase Contractility in Heart Failure).
METHODS: Patients (n=448) were randomized 1:1:1 to placebo, 25 mg of OM BID, or 
to pharmacokinetically guided dose titration (OM-PK) for 20 weeks. The Kansas 
City Cardiomyopathy Questionnaire was administered to assess HRQL at baseline, 
16 weeks, and 20 weeks. The primary scores of interest were the Total Symptom 
Score, Physical Limitation Scale, and Clinical Summary Score.
RESULTS: Mean change in score from baseline to 20 weeks for the Total Symptom 
Score was 5.0 (95% CI, 1.8-8.1) for placebo, 6.6 (95% CI, 3.4-9.8) for OM 25 mg 
(P=0.32 versus placebo), and 9.9 (95% CI, 6.7-13.0) for OM-PK (P=0.03 versus 
placebo); for the Physical Limitation Scale, it was 3.1 for placebo (95% CI, 
-0.3 to 6.6), 6.0 (95% CI, 3.1-8.9) for OM 25 mg (P=0.12), and 4.3 (95% CI, 
0.7-7.9) for OM-PK (P=0.42); for the Clinical Summary Score, it was 4.1 (95% CI, 
1.4-6.9) for placebo, 6.3 (95% CI, 3.6-9.0) for OM 25 mg (P=0.19), and 7.0 (95% 
CI, 4.1-10.0) for OM-PK (P=0.14). Differences between OM and placebo were 
greater in patients who were more symptomatic at baseline.
CONCLUSIONS: HRQL as measured by the Total Symptom Score improved in patients 
with heart failure with reduced ejection fraction assigned to the OM-PK group 
relative to placebo. Ongoing trials are prospectively testing whether OM 
improves symptoms and HRQL in heart failure with reduced ejection fraction. 
Registration: URL: https://www.clinicaltrials.gov; Unique identifier: 
NCT01786512.