Omecamtiv mecarbil in heart failure with reduced ejection fraction: systematic review and meta-analysis

Type of funding sources: None.

Heart failure (HF) is a growing public health challenge worldwide, with high rates of mortality and morbidity. Omecamtiv Mecarbil (OM) is a cardiac myosin activator and the first of a novel class of myotropes, agents that directly improve myocardial function by selectively improving cardiac sarcomere function. Data on its effect on cardiovascular outcomes remains scarce.

To evaluate the safety and efficacy of Omecamtiv Mecarbil in Heart Failure with Reduced Ejection Fraction (HFrEF) and its effect on mid-term clinical outcomes.

We systematically searched MEDLINE/Pubmed, CENTRAL, clinicaltrials.gov, and the International Clinical Trials Registry Platform for randomized clinical trials (RCTs) evaluating OM safety and efficacy in HFrEF. Outcomes of interest included all-cause mortality, cerebrovascular events, hospitalization, myocardial infarction (MI), anginal events, atrial fibrillation (AF) or flutter, and hypotension. Data screening and extraction was performed by two independent reviewers. We used a random-effects model using the Dersimonian-Laird and Mantel-Haenszel methods to calculate the risk ratio (RR) with 95% confidence intervals.

A total of 232 records were identified, of which six RCTs (N = 9,547; Omecamtiv: 4,889; Placebo: 4,658) met inclusion criteria. The average age was 64.4 years (standard deviation (SD): 0.82), and 79.0% (N = 7,538) were males. The weighted follow-up duration was 19.4 months. OM was associated with a significant reduction in the incidence of cerebrovascular events (RR: 0.68; 95% CI: 0.51 to 0.91). Moreover, OM was associated with a significant increase in the risk of hypotension (RR: 1.45; 95% CI: 1.03 to 2.02), compared to placebo when utilized as an adjuvant therapy to HF guideline-directed medical therapy (GDMT). No statistically significant difference was noted with all-cause mortality (RR: 1.00; 95% CI: 0.93 to 1.07), hospitalization (RR: 0.96; 95% CI: 0.90 to 1.03), incidence of atrial fibrillation or flutter (RR: 0.79; 95% CI: 0.61 to 1.02), anginal events (RR: 1.32; 95% CI: 0.92 to 1.88) or myocardial infarction (RR: 1.07; 95% CI: 0.84 to 1.36). Heterogeneity was low (I2 = 0%) in all analyses.