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).

Study Design

  • Randomized
  • Parallel
  • Placebo

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%

Inclusion criteria:

  • 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

Exclusion criteria:

  • 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%

Principal Findings:

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). The only subgroup which demonstrated possible treatment interaction was LVEF. Subjects with LVEF ≤ median appeared to benefit from omecamtiv mecarbil vs. placebo, while those with LVEF > median did not appear to benefit from omecamtiv mecarbil vs. placebo.

Secondary outcomes:

  • 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


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; however, 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. There was possibly a greater treatment effect with omecamtiv mecarbil among those with LVEF ≤28%.


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 2020;Nov 13:[Epub ahead of print].

Presented by Dr. John R. Teerlink at the American Heart Association Virtual Scientific Sessions, November 13, 2020.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Vascular Medicine

Keywords: AHA20, AHA Annual Scientific Sessions, Adrenergic beta-Antagonists, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Cardiac Myosins, Heart Failure, Natriuretic Peptides, Neprilysin, Stroke Volume, Ventricular Dysfunction, Left

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