Black patients with heart failure with reduced ejection fraction (HFrEF) treated with omecamtiv mecarbil experience a similar benefit regarding time to a first HF event or cardiovascular death compared with White patients, according to a study in JACC: Heart Failure.
The Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) trial evaluated the effects of omecamtiv mecarbil in patients with HFrEF. The analysis assessed the efficacy and safety of omecamtiv mecarbil in self-identified Black patients compared with White patients.
Eligible participants were aged 18 to 85 years; had symptomatic HF (New York Heart Association functional class II, III, or IV); had left ventricular EF (LVEF) of 35% or less; had increased natriuretic peptide levels; and were hospitalized for HF, had an urgent visit to the emergency department, or had been hospitalized for HF within 1 year before screening.
The patients were randomly assigned in a 1:1 ratio to receive omecamtiv mecarbil or placebo along with standard care. The omecamtiv mecarbil doses were 25 mg, 37.5 mg, or 50 mg twice daily and were adjusted based on plasma levels of the drug. Postrandomization assessments were conducted at week 2, then every 2 weeks until week 8. After week 8, assessments took place at week 12, 24, 36, 48, and then every 16 weeks.
The primary composite outcome was time to first HF event or death from cardiovascular causes.
A total of 8232 patients were included, of whom 6.8% self-identified as Black. Black patients’ mean age was 58 years, 34% were women, and their mean LVEF was 24%. The mean age among 1129 White patients was 65 years, 24% were women, and their mean LVEF was 25%.
Black patients had 260 primary events (48.6%), and White patients had 484 primary events (42.9%). Black patients were more frequently women, younger, had lower LVEF, were more likely to have hypertension, and were less likely to have atrial arrhythmias or ischemic etiology vs White patients (all P ≤.001).
The primary event rate among Black patients was 38 per 100 patient-years vs 31 per 100 patient-years in White patients (P =.017). The hazard ratio (HR) for primary events in Black vs White patients was 1.33 (95% CI, 1.13-1.56), after adjustment for age, sex, and country. Black patients also had a greater risk for HF hospitalization, with an adjusted HR of 1.38, (95% CI, 1.15-1.65). No significant difference was observed for cardiovascular mortality in the adjusted model (HR, 0.87; 95% CI, 0.67-1.13).
The estimated treatment effect on the primary endpoint for Black patients (HR, 0.83; 95% CI, 0.65-1.06) was comparable to that in White patients in the same countries (HR, 0.88; 95% CI, 0.73-1.05). For absolute event rates, the estimated effect of omecamtiv mecarbil for Black patients was a decreased primary event rate of 7.7 events per 100 patient-years (95% CI, -17.9 to 2.4) vs saving 6.0 events per 100 patient-years in White patients (95% CI, -11.9 to 0.0).
The investigators noted that the only nominally significant interaction between treatment and race that effected clinical outcomes was in blood pressure. In Black patients, omecamtiv mecarbil was associated with a 3.4-mm Hg increase in systolic blood pressure (95% CI, 0.2-6.7). For White patients, no significant change in systolic blood pressure occurred (-0.7 mm Hg; 95% CI, 2.6-1.3), with an unadjusted interaction P-value of .02.
The researchers noted that the trial was not designed to be adequately powered for race-based stratified analyses of the primary and secondary endpoints, and they did not have data on socioeconomic status or other social determinants of health.
“These data underscore the importance of diverse patient enrollment in clinical trials, specifically including groups that are traditionally under-represented such as Black patients, so patients and providers can have confidence that overall study findings can be safely applied to these subgroups,” wrote the investigators.
Disclosure: The GALACTIC-HF trial was funded by Amgen, Cytokinetics Inc, and Servier Laboratories. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Lanfear DE, Njoroge JN, Adams KF, et al. Omecamtiv mecarbil in Black patients with heart failure and reduced ejection fraction: insights from GALACTIC-HF. J Am Coll Cardiol HF. Published online February 1, 2023. doi: 10.1016/j.jchf.2022.11.021