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.

Description:

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

Interpretation:

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%.

References:

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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