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N-terminal pro-B-type natriuretic peptide (NT-proBNP) is predictive of both outcomes and response to treatment in patients with heart failure with reduced ejection fraction (HFrEF).To examine the effect of the cardiac myosin activator omecamtiv mecarbil according to baseline NT-proBNP level in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure trial (GALACTIC-HF).The primary outcome was the composite of a worsening HF event (urgent clinic visit, emergency department visit, or hospitalization) or cardiovascular death. We prespecified analysis of the effect of treatment according to baseline NT-proBNP (≤median,median), excluding individuals with AF/AFL.Of the 8232 patients analyzed, 8206 had an available baseline NT-proBNP measurement. Among the 5971 patients not in AF/AFL, the median (Q1, Q3) NT-proBNP level was 1675 (812-3579) pg/ml. Hazard ratios (HR) for the effect of omecamtiv mecarbil, compared with placebo, for the primary endpoint in patients without AF/AFL were: ≤median 0.94 (95% CI, 0.80-1.09),median 0.81 (0.73-0.90) [P-interaction = 0.095]; for the overall population (including patients with AF/AFL) the HRs were ≤ median 1.01 (0.90-1.15) and median 0.88 (0.80-0.96) [P-interaction = 0.035]. There was an interaction between treatment and NT-proBNP, examined as a continuous variable, with greater effect of omecamtiv mecarbil on the primary outcome in patients with a higher baseline NT-proBNP (P-interaction = 0.086).In GALACTIC-HF, the benefit of omecamtiv mecarbil appeared to be larger in patients with higher baseline NT-proBNP levels, especially in patients without AF/AFL. This article is protected by copyright. All rights reserved.