Effects of Omecamtiv Mecarbil on Symptoms and Health-Related Quality of Life in Patients with Chronic Heart Failure: Results from the COSMIC-HF Study.

Background: Chronic HF with reduced ejection fraction (HFrEF) impairs health related quality of life (HRQL). Omecamtiv mecarbil, a novel activator of cardiac myosin, improves left ventricular systolic function and remodeling and reduces natriuretic peptides. We sought to evaluate the effect of omecamtiv mecarbil on symptoms and HRQL in patients with chronic HFrEF and elevated natriuretic peptides enrolled in the COSMIC-HF trial. Methods: Patients (n = 448) were randomized 1:1:1 to placebo, 25 mg of omecamtiv mecarbil twice daily (OM 25 mg), or to pharmacokinetically-guided dose titration (OM-PK) for 20 weeks. The Kansas City Cardiomyopathy Questionnaire (KCCQ) was administered to assess HRQL at baseline, 16 weeks, and 20 weeks. The primary scores of interest were the Total Symptom Score (TSS), Physical Limitation Scale (PLS), and Clinical Summary Score (CSS). Results: Mean change in score from baseline to 20 weeks for the TSS 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 vs placebo), and 9.9 (95%CI: 6.7-13.0) for OM-PK (p = 0.03 vs placebo); for the PLS, it was 3.1 for placebo (95%CI: -0.3-6.6), 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 CSS, 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 omecamtiv mecarbil and placebo were greater in patients who were more symptomatic at baseline. Conclusions: HRQL as measured by the TSS improved in patients with HFrEF assigned to omecamtiv mecarbil (OM-PK group) relative to placebo. Ongoing trials are prospectively testing whether omecamtiv mecarbil improves symptoms and HRQL in HFrEF. Registration: clinicaltrials.gov; Unique Identifier: NCT01786512.