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

Abstract

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.

Keywords: heart failure; longitudinal studies; quality of life; stroke volume; systole.

Conflict of interest statement

Dr Felker has received research grants from the National Heart, Lung, and Blood Institute (NHLBI), American Heart Association, Amgen, Bayer Merck, Cytokinetics, Myokardia, Bayer, and Roche Diagnostics; he has acted as a consultant to Novartis, Amgen, Bristol Myers Squibb, Cytokinetics, Medtronic, Cardionomic, V-Wave, Myokardia, Innolife, EBR Systems, Arena, Abbott, Roche Diagnostics, Alnylam, LivaNova, Eidos Therapeutics, Rocket Pharma, Reprieve, and SC Pharma. Dr Solomon has received research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, Glaxo Smith Kline, Ionis, Lone Star Heart, Mesoblast, MyoKardia, National Institutes of Health/NHLBI, Neurotronik, Novartis, Respicardia, Sanofi Pasteur, and Theracos and has consulted for Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, Gilead, Glaxo Smith Kline, Ironwood, Merck, Myokardia, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, Cardiac Dimensions, Tenaya, Sanofi Pasteur, Dinaqor, Tremeau, CellProThera, and Moderna. Dr McMurray reports consultancies paid to Glasgow University with Alnylam, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Cardurion, Cytokinetics, DalCor, Glaxo Smith Kline, Merck, Novartis, Pfizer, Servier Theracos, and Vifor-Fresenius. Dr Cleland reports grants and personal fees from Bristol Myers Squibb, Amgen, Bayer, Novartis, Myokardia, Pharmacosmos, Vifor, Bristol Myers Squibb, and Servier; personal fees from Abbott; and personal fees and nonfinancial support from Medtronic. Drs Abbasi, Zhang, and Globe are employees of Amgen. Dr Malik is an employee of Cytokinetics. Dr Teerlink reports research grants and consulting fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Cytokinetics, EBR Systems, Medtronic, Merck, and Novartis.

Figures

Figure 1.

Mean change in Kansas City Cardiomyopathy Questionnaire from baseline through weeks 16 and 20 for Total Symptom Score (TSS), Physical Limitations Score (PLS), and Clinical Summary Score (CSS). Error bars show ±SE. OM indicates omecamtiv mecarbil; and PK, pharmacokinetic. *P≤0.05, all other comparisons, P>0.05. Placebo = blue bars, OM 25mg = Orange bars, OM PK = Grey bars.

Figure 2.

Change in Total Symptom Score (TSS), Physical Limitations Score (PLS), and Clinical Summary Score (CSS) based on symptom severity at baseline. Placebo = blue bars, OM 25mg = Orange bars, OM PK = Grey bars. OM indicates omecamtiv mecarbil; and PK, pharmacokinetic.