Treatment benefits with cardiac myosin activator increase with decreasing baseline EFs in HFrEF

Impact of Ejection Fraction On The Therapeutic Effect Of Omecamtiv Mecarbil In Patients With Heart Failure And Reduced Ejection Fraction: A Secondary Analysis From GALACTIC-HF

News - May 31, 2021

Presented at ACC.21 by John R. Teerlink, MD (San Francisco, CA, USA)

Introduction and methods

The GALACTIC-HF trial demonstrated that omecamtiv mecarbil, a cardiac myosin activator, reduces the primary outcome of a HF event or CV death in patients with LVEF≤35%, compared to placebo. Furthermore, subgroup results showed that the largest treatment benefit of omecamtiv mecarbil occurred in patients with baseline LVEF ≤28%. This subanalysis of GALACTIC-HF further assessed the influence of baseline EF on the treatment effect of omecamtiv mecarbil in patients with HFrEF.

GALACTIC-HF was a multicentered, randomized, double-blind, placebo-controlled, event-driven phase 3 study that included patients with HFrEF. Inclusion criteria were: chronic HF, NYHA II-IV, LVEF ≤35%, elevated BNP/NT-proBNP, SBP ≥85 mm Hg, eGFR ≥20 mL/min/1.73m², and managed with standard HF therapies. Both patients hospitalized for HF (inpatients) and patients in need of an urgent hospital visit or hospitalization for HF within 1 year prior to screening (outpatients) were included in the trial. Patients (n=8256) were randomized (1:1) to omecamtiv mecarbil (using a pharmacokinetic-guided dose selection) or placebo. The primary endpoint was a composite of time to first HF event or CV death. For this subanalysis, patients were stratified to quartiles of baseline LVEF.


  • The treatment effect of omecamtiv mecarbil in patients with HFrEF increased with decreasing baseline EF.
  • Patients in the LVEF ≤22% and LVEF 23%-28% quartiles receiving omecamtiv mecarbil had a 15% (HR 0.85, 95% CI: 0.74-0.97, P=0.016) and 17% (HR 0.83, 95% CI: 0.73-0.95, P=0.005) relative risk reduction for time to first HF event or CV death compared to no difference for those in the LVEF 29% and LVEF ≥33% quartiles.
  • In HFrEF with baseline LVEF ≤22%, the number-needed-to-treat with omecamtiv mecarbil to prevent one first time HF event or CV death over 3 years was 11.8 patients.
  • There were no differences in serious adverse events, ischemic events, or arrhythmic events between the omecamtiv mecarbil group and placebo group across the range of EF. Also, no differences in adverse effects on blood pressure, heart rate, potassium homeostasis or renal function were observed.


The GALACTIC-HF subanalysis showed that treatment effect of omecamtiv mecarbil in patients with HFrEF was associated with greater reductions in HF events and CV death as baseline EF decreased.


The discussant Ileana Piña, MD (Mount Pleasant, MI, USA) thanked the presenter John Teerlink for conducting this subanalysis. She continued and asked herself how long we have been waiting for a drug that we can use in HFrEF patients with decreasing ejection fractions. These are people that are recommended for a heart transplant or in need of mechanical assistance. The finding that omecamtiv mecarbil does not increase cardiac oxygen demand is very encouraging. Also the fact that the drug can be given in an outpatient setting is really an advancement.

Omecamtiv mecarbil did not change mortality rate, something she said she was not surprised about due to the poor health status of these patients. But, she said, this drug will buy physicians some time to get these patients on the right therapy.

Piña continued that she would be very interested in a subanalysis of GALACTIC-HF looking at sex- and regional differences. She concluded the discussion by saying that the findings of GALACTIC-HF are very encouraging for very sick patients with HFrEF.

– Our coverage of ACC.21 is based on the information provided during the congress –

The study was simultaneously published in the J Am Coll Cardiol.

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