In the primary endpoint, patients with severe HF had a 20% risk reduction compared to no significant treatment benefit in patients without severe HF.
Although substantial improvements in medical therapies for patients with heart failure with reduced ejection fraction (HFrEF) have occurred, many patients' conditions still worsen over time, due to intolerance of the available therapies.
Through a post-hoc analysis of the Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) randomized clinical trial of patients with HFrEF, investigators in a recent study evaluated the efficacy and safety of omecamtiv mecarbil for the treatment of patients with severe HF.
Led by G. Michael Felker, MD, Duke Clinical Research Institute, the team observed the use of omecamtiv mecarbil therapy may provide a clinically meaningful reduction of time to first HF event or CV death in patients with HF.
The GALACTIC-HF was a global double-blind, placebo-controlled phase 3 randomized clinical trial conducted at multiple centers between January 2017 - August 2020.
Under the study perimeters, a total of 8232 patients with symptomatic HF and left ventricular ejection fraction of ≤35% were randomized at a 1:1 ratio to receive omecamtiv mecarbil or placebo, with a median follow-up of 21.8 months.
Primary outcomes for the study included a composite of time to first HF event or death from cardiovascular causes, followed by time to CV death and safety and tolerability measures.
Investigators noted severe HF was defined as the presence of New York Heart Association symptom class III to IV, left ventricular ejection fraction of ≤30%, ≥2 hospitalizations for HF within 12 months, and evidence of severe function impairment measured by cardiopulmonary exercise testing.
In the matter of statistical analysis, outcomes for patients with severe HF versus patients without severe HF were compared using Cox proportional hazards models and Kaplan-Meier curves.
Out of a total of 8232 patients enrolled in the GALACTIC-HF clinical trial, 2258 patients met the criteria for severe HF. Specifically, these patients had a mean age of 64.5 years, with 1781 men (78.9%).
The data show patients with severe HF, in comparison to those without, had increased markers indicating severe disease, including lower LVEF (mean, 23.4% versus 27.8%) and higher NYHA symptom class (class IV: 173 patients versus 75 patients).
During randomization, 1106 patients were randomized to the omecamtiv mecarbil group and 1152 patients were randomized to the placebo group.
Investigators observed patients classified with severe HF had greater treatment benefit from omecamtiv mecarbil, in comparison to those without severe HF.
In terms of the primary end point, patients with severe HF had a 20% risk reduction (hazard ratio, 0.80; 95% CI, 0.71 - 0.90), while patients without severe HF had no significant treatment benefit (HR, 0.99; 95% CI, 0.91 - 1.08; P for HF severity by treatment interaction = .005).
Investigators saw similar results for CV death for patients with severe HF (HR, 0.88; 95% CI, 0.75 - 1.03) versus those without severe HF (HR, 1.10; 95% CI, 0.97 - 1.25, P = .03 for interaction).
Additionally, the benefit of omecamtiv mecarbil therapy was greatest in patients who met all 3 severe HF criteria, already considered the group with the highest overall risk profile. In the primary endpoint, a 20% relative risk reduction was broken down to a risk reduction of 8.3 events per 100 patient-years.
Data show no significant changes in systolic blood pressure, worsening of kidney function, or worsening of potassium level, in comparison to placebo.
“Overall, these data support both the efficacy and tolerability of omecamtiv mecarbil in a patient population that may be difficult to treat effectively with other HF drugs,” investigators wrote.
The study, “Assessment of Omecamtiv Mecarbil for the Treatment of Patients With Severe Heart Failure: A Post Hoc Analysis of Data From the GALACTIC-HF Randomized Clinical Trial,” was published in JAMA Cardiology.