Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure - GALACTIC-HF
Contribution To Literature:
The GALACTIC-HF trial showed that omecamtiv mecarbil was superior to placebo at improving cardiovascular outcomes.
The goal of the trial was to evaluate the selective cardiac myosin activator omecamtiv mecarbil compared with placebo among patients with heart failure with reduced ejection fraction (HFrEF).
Patients with HFrEF were randomized to omecamtiv mecarbil (n = 4,120) versus placebo (n = 4,112). Patients in the omecamtiv mecarbil received 25 mg, 37.5 mg, or 50 mg twice daily based on plasma levels of the drug.
- Total number of enrollees: 8,256
- Duration of follow-up: median of 21.8 months
- Mean patient age: 65 years
- Percentage female: 21%
- Percentage with diabetes: 40%
- Patients 18-85 years of age with chronic HF symptoms
- New York Heart Association class II, III, or IV symptoms
- Left ventricular EF (LVEF) ≤35%
- N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≥400 pg/ml
- BNP ≥125 pg/ml
- Hemodynamic instability requiring mechanical support or intravenous medication
- Systolic blood pressure <85 mm Hg
- Estimated glomerular filtration rate <20 ml/min/1.73 m2
- Recent acute coronary syndrome of cardiovascular procedure
Other salient features/characteristics:
- Mean LVEF: 27%
- Angiotensin-converting enzyme inhibitor, angiotensin-receptor blocker, or angiotensin receptor-neprilysin inhibitor (ARNI): 87%
- ARNI: 20%
- Beta-blocker: 94%
- Mineralocorticoid-receptor antagonist: 78%
- Sodium-glucose cotransporter 2 (SGLT2) inhibitor: 2.5%
The primary outcome, cardiovascular death or HF event at a median of 21.8 months, occurred in 37.0% of the omecamtiv mecarbil group compared with 39.1% of the placebo group (p = 0.03).
- Cardiovascular death: 19.6% of the omecamtiv mecarbil group compared with 19.4% of the placebo group (p = 0.86)
- All-cause death: 25.9% of the omecamtiv mecarbil group compared with 25.9% of the placebo group
- Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) total symptom score at 24 weeks: 23.7 in the omecamtiv mecarbil group compared with 21.2% in the placebo group
Baseline ejection fraction and treatment effect of omecamtiv:
- LVEF ≤28%; primary outcome for omecamtiv vs. placebo (hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.77-0.92)
- LVEF >28%; primary outcome for omecamtiv vs. placebo (HR 1.04, 95% CI 0.94-1.16; p for interaction = 0.003)
Effect of baseline atrial fibrillation on treatment effect of omecamtiv mecarbil:
- Patients with baseline atrial fibrillation had reduced benefit from omecamtiv mecarbil (p for interaction = 0.012)
- Lack of treatment effect was mostly observed among those with baseline atrial fibrillation who were also receiving digoxin (p for interaction = 0.007)
Effect of omecamtiv mecarbil according to blood pressure:
- Subjects were stratified according to systolic blood pressure ≤100 mm Hg (17.9%) and systolic blood pressure >100 mm Hg (82.1%)
- Among those with systolic blood pressure ≤100 mm Hg, omecamtiv mecarbil vs. placebo had the following association: hazard ratio 0.81, 95% confidence interval 0.70-0.94
- Among those with systolic blood pressure >100 mm Hg, omecamtiv mecarbil vs. placebo had the following association: hazard ratio 0.95, 95% confidence interval 0.88-1.03, p for interaction = 0.051
Among patients with HFrEF on good background medical therapy, the selective cardiac myosin activator omecamtiv mecarbil was superior to placebo. Omecamtiv mecarbil was associated with a reduction in the primary composite outcome, which was greater among those with LVEF ≤28% and among those with systolic blood pressure ≤100 mm Hg. Omecamtiv mecarbil was less effective among those with baseline atrial fibrillation; however, this lack of treatment effect was mostly observed among those with atrial fibrillation who were receiving digoxin. There was no benefit in outcomes of cardiovascular death, all-cause death, or change in KCCQ total symptoms score. Serious adverse events were similar between treatment groups.
Highlighted text has been updated as of June 23, 2022.
Metra M, Pagnesi M, Claggett BL, et al., on behalf of the GALACTIC-HF Investigators. Effects of Omecamtiv Mecarbil in Heart Failure With Reduced Ejection Fraction According to Blood Pressure: The GALACTIC-HF Trial. Eur Heart J 2022;May 22:[Epub ahead of print].
Solomon SD, Claggett BL, Miao ZM, et al. Influence of Atrial Fibrillation on Efficacy and Safety of Omecamtiv Mecarbil in Heart Failure: the GALACTIC-HF Trial. Eur Heart J 2022;43:2212-20.
Editorial Comment: van der Meer P, Rienstra M, van Veldhuisen DJ. A Deleterious Interaction Between Omecamtiv Mecarbil and Atrial Fibrillation in Patients With Heart Failure: An Influence of Digoxin? Eur Heart J 2022;43:2221-3.
Teerlink JR, Diaz R, Felker M, et al., on behalf of the GALACTIC-HF Investigators. Effect of Ejection Fraction on Clinical Outcomes in Patients Treated With Omecamtiv Mecarbil in GALACTIC-HF. J Am Coll Cardiol 2021;78:97-108.
Presented by Dr. John R. Teerlink at the American College of Cardiology Virtual Annual Scientific Session (ACC 2021), May 17, 2021.
Teerlink JR, Diaz R, Felker GM, et al., on behalf of the GALACTIC-HF Investigators. Cardiac Myosin Activation With Omecamtiv Mecarbil in Systolic Heart Failure. N Engl J Med 2021;384:105-16.
Presented by Dr. John R. Teerlink at the American Heart Association Virtual Scientific Sessions, November 13, 2020.
Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Vascular Medicine
Keywords: ACC21, ACC Annual Scientific Session, AHA20, AHA Annual Scientific Sessions, Adrenergic beta-Antagonists, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Atrial Fibrillation, Blood Pressure, Cardiac Myosins, Heart Failure, Natriuretic Peptides, Neprilysin, Stroke Volume, Ventricular Dysfunction, Left
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