KCCQ total symptom score, clinical outcome measures, and adverse events associated with omecamtiv mecarbil for heart failure with reduced ejection fraction: a systematic review and meta-analysis of randomized controlled trials.

Background: Omecamtiv mecarbil (OM) is a direct myosin activator that augments left ventricular systolic function. This review compares OM to placebo by evaluating its effect on clinical outcomes and adverse events in patients with heart failure with reduced left ventricular ejection fraction.

Methods And Results: A literature search of multiple databases for randomized controlled trials (RCTs) investigating OM versus placebo was undertaken. Six RCTs comprising 9596 patients were included. Use of OM was associated with a reduced risk of stroke (RR: 0.69; 95% CI 0.52-0.92). There was no significant mean difference (MD) change in the KCCQ total symptom score (MD: 1.82, 95% CI - 1.33 to 4.97), all-cause death (RR: 1.00; 95% CI 0.93-1.07), hospital readmissions (RR: 0.96; 95% CI 0.90-1.03), myocardial infarction (RR: 1.05; 95% CI 0.83-1.33), cardiovascular death (RR: 1.01; 95% CI 0.92-1.10), heart failure (HF) events (RR: 0.95; 95% CI 0.89-1.02), or a composite of cardiovascular death or HF events (RR: 0.97; 95% CI 0.93-1.02). In addition, OM was associated with an increased risk of dizziness (RR: 1.25; 95% CI 1.04-1.50) and hypotension (RR: 1.17; 95% CI 1.01-1.36). Other adverse events including ventricular tachyarrhythmias, (RR: 0.95; 95% CI 0.82-1.11), supraventricular tachyarrhythmias and atrial fibrillation/flutter (RR: 0.73; 95% CI 0.46-1.18), dyspnea (RR: 1.00; 95% CI 0.86-1.18), and acute renal injury (RR: 0.88; 95% CI 0.60-1.27) were not significant.

Conclusion: OM is generally well tolerated. We identified a reduced risk of stroke with use of OM. However, there was no improvement in other clinical outcomes or quality of life. Study protocol was registered in PROSPERO international prospective register of systematic reviews (CRD42022348423).