Omecamtiv Mecarbil Shows Promise in Patients with Severe Heart Failure
Results of a GALACTIC-HF post-hoc analysis suggest a role for omecamtiv mecarbil in an HF population that remains difficult to treat effectively.
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In a post hoc analysis of the GALACTIC-HF trial, omecamtiv mecarbil reduced the primary endpoint of time to first heart failure (HF) event or CV death among patients with severe HF, findings that may support a role for the cardiac-specific myosin activator in a patient population with limited treatment options, study authors write in JAMA Cardiology.
The GALACTIC-HF global, double-blind, phase 3, placebo-controlled trial randomized 8232 patients with symptomatic HF (NYHA symptom class II-IV) and left ventricular ejection fraction (LVEF) ≤35% to receive omecamtiv mecarbil or placebo and followed them for a median of 21.8 months.
The current analysis focused on the safety and efficacy of omecamtiv mecarbil in a subgroup of GALACTIC-HF patients classified as having severe HF vs those without severe HF. Investigators defined severe HF as presence of NYHA symptom class III-IV, LVEF ≤30%, and hospitalization for HF within the previous 6 months.
Led by G. Michael Felker, MD, MHS professor of medicine and vice chief for clinical research of Duke Cardiology and director of cardiovascular research at the Duke Clinical Research Institute, the researchers defined the primary end point as time to first HF event or cardiovascular (CV) death and included time to CV death and drug safety and tolerability as secondary end points.
RESULTS
The analysis included 2,258 patients (mean age, 65 years; 79% men) who met the specified criteria for severe HF from the original GALACTIC-HF cohort of 8,232 patients. Among these patients, 1,106 were randomly assigned to omecamtiv mecarbil and 1,152 to placebo.
Felker et al report that omecamtiv mecarbil significantly reduced the primary endpoint in patients with severe HF (hazard ratio [HR], 0.8; 95% confidence interval [CI], 0.71-0.9), but had no significant impact in patients without severe HF (HR, 0.99; 95% CI, 0.91-1.08; Pinteraction= .005). Results for CV death were similar between the 2 groups: HR severe FH, 0.88; 95% CI, 0.75-1.03) vs HR without severe HF, 1.1; 95% CI, 0.97-1.25; Pinteraction= .03).
The authors write that omecamtiv mecarbil therapy was well tolerated in this vulnerable subset of HF patients, “with no significant changes in blood pressure, kidney function or potassium level compared with placebo.”
Writing in an accompanying editorial, Clyde W. Yancy, MD, MSc, and colleagues say that these results provide a clinically evident demarcation of a potentially new stage of HF, “specifically patients with [HF with reduced ejection fraction] who are receiving effective guideline-directed medical therapy (ie, patients with stage C HF) but have progressive or severe symptoms that do not yet reach the threshold for advanced therapies (ie, stage D HF). This demarcation is not a quirk of recruitment within a large clinical trial but a true, common and actionable clinical dilemma.”
Yancy, vice dean for diversity and inclusion, chief of cardiology, Magerstadt Professor and professor of medicine and medical social sciences at Northwestern University Feinberg School of Medicine, et al, also say that despite the limitations associated with post-hoc analysis, these results “offer direction that may guide the use of a new therapy, identify an important and expanding population with severe HF, and offer the potential for salutary clinical benefits.”
Reference: Felker GM, Solomon SD, Claggett B, et al. Assessment of omecamtiv mecarbil for treatment of patients with severe heart failure: a post-hoc analysis of data from the GALACTIC-HF randomized clinical trial. JAMA Cardiology. Published online October 13, 2021.
Editorial: Yancy CW, Hernandez AF, Fonarow GC. Identifying treatments for stage C2 heart failure. JAMA Cardiol. Published online October 13, 2021.
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