Physicians' Academy for Cardiovascular Education

Myosin activator less effective in patients with HFrEF and AF or atrial flutter

News - July 2, 2021

Influence of Atrial Fibrillation on Efficacy of Omecamtiv Mecarbil in Heart Failure: The GALACTIC-HF Trial

Presented at the ESC HF 2021 by Scott Solomon (Boston, MA, USA)

Introduction and methods

The GALACTIC-HF trial demonstrated that omecamtiv mecarbil, a cardiac myosin activator, reduces the composite outcome of a first HF event or CV death in patients with HFrEF, compared to placebo.

AF is common in patient with HF and contributes substantially to morbidity and mortality. Although AF has not influenced the treatment effect of RAASi, it may modify the treatment effect of beta-blockers. The presence of AF or atrial flutter (AFL) at baseline in the GALACTIC-HF trial modified the effectiveness of omecamtiv mecarbil with treatment being less effective in patients with AF or AFL at baseline.

This subanalysis assessed the influence of baseline AF or AFL on the treatment effectiveness of omecamtiv mecarbil in patients with HFrEF and further explored potentially other factors that may have influenced the effectiveness.

The GALACTIC-HF trial was a multicenter, international, randomized, double-blind, placebo-controlled, event-driven, phase 3 study. Inclusion criteria were: chronic HF, NYHA II-IV, LVEF ≤35%, elevated BNP/NT-proBNP that had to be 3 fold increased in patients with baseline AF/AFL, SBP ≥85 mm Hg, and eGFR ≥20 mL/min/1.73m². The trial included patients who were hospitalized for HF (inpatients) or who had been hospitalized or had an urgent visit to the hospital due to HF within 1 year prior to screening (outpatients). The total amount of patients with AF/AFL (n=2245) at baseline was capped at ~25%. Patients were randomized (1:1) to omecamtiv mecarbil (using a pharmacokinetic-guided dose selection) or placebo in addition to standard therapy.



AF or AFL modified the treatment effect of omecamtiv mecarbil, with a greater treatment benefit in HFrEF patients without AF/AFL at baseline. Treatment effect modifications were prominent in digoxin treated patients with AF/AFL with almost no effect modification in non-users with AF or AFL. However, digoxin did not modify the treatment effect in patients without AF/AFL.

These results, said Scott Solomon, suggest that caution should be exercised when treating patients with HFrEF and in AF/AFL with both digoxin and omecamtiv mecarbil.

– Our coverage of ESC HF 2021 is based on the information provided during the congress –

Share this page with your colleagues and friends: