TY - JOUR

T1 - Effect of Ejection Fraction on Clinical Outcomes in Patients Treated With Omecamtiv Mecarbil in GALACTIC-HF

AU - Teerlink, John R.

AU - Diaz, Rafael

AU - Felker, G. Michael

AU - McMurray, John J.

AU - Metra, Marco

AU - Solomon, Scott D.

AU - Biering-Sorensen, Tor

AU - Boehm, Michael

AU - Bonderman, Diana

AU - Fang, James C.

AU - Lanfear, David E.

AU - Lund, Mayanna

AU - Momomura, Shin-Ichi

AU - O'Meara, Eileen

AU - Ponikowski, Piotr

AU - Spinar, Jindrich

AU - Flores-Arredondo, Jose H.

AU - Claggett, Brian L.

AU - Heitner, Stephen B.

AU - Kupfer, Stuart

AU - Abbasi, Siddique A.

AU - Malik, Fady

AU - GALACTIC HF Investigators

PY - 2021

Y1 - 2021

N2 - BACKGROUND In GALACTIC-HF (Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure) (n = 8,256), the cardiac myosin activator, omecamtiv mecarbil, significantly reduced the primary composite endpoint (PCE) of time-to-first heart failure event or cardiovascular death in patients with heart failure and reduced ejection fraction (EF) (OBJECTIVES The purpose of this study was to evaluate the influence of baseline EF on the therapeutic effect of omecamtiv mecarbil.METHODS Outcomes in patients treated with omecamtiv mecarbil were compared with placebo according to EF.RESULTS The risk of the PCE in the placebo group was nearly 1.8-fold greater in the lowest EF (= 33%) quartile. Amongst the pre-specified subgroups, EF was the strongest modifier of the treatment effect of omecamtiv mecarbil on the PCE (interaction as continuous variable, p = 0.004). Patients receiving omecamtiv mecarbil had a progressively greater relative and absolute treatment effect as baseline EF decreased, with a 17% relative risk reduction for the PCE in patients with baseline EF = 33% (n =1,750; hazard ratio: 0.99; 95% confidence interval: 0.84 to 1.16; interaction as EF by quartiles, p = 0.013). The absolute reduction in the PCE increased with decreasing EF (EFCONCLUSIONS In heart failure patients with reduced EF, omecamtiv mecarbil produced greater therapeutic benefit as baseline EF decreased. These findings are consistent with the drug's mechanism of selectively improving systolic function and presents an important opportunity to improve the outcomes in a group of patients at greatest risk. Published by Elsevier on behalf of the American College of Cardiology Foundation.

AB - BACKGROUND In GALACTIC-HF (Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure) (n = 8,256), the cardiac myosin activator, omecamtiv mecarbil, significantly reduced the primary composite endpoint (PCE) of time-to-first heart failure event or cardiovascular death in patients with heart failure and reduced ejection fraction (EF) (OBJECTIVES The purpose of this study was to evaluate the influence of baseline EF on the therapeutic effect of omecamtiv mecarbil.METHODS Outcomes in patients treated with omecamtiv mecarbil were compared with placebo according to EF.RESULTS The risk of the PCE in the placebo group was nearly 1.8-fold greater in the lowest EF (= 33%) quartile. Amongst the pre-specified subgroups, EF was the strongest modifier of the treatment effect of omecamtiv mecarbil on the PCE (interaction as continuous variable, p = 0.004). Patients receiving omecamtiv mecarbil had a progressively greater relative and absolute treatment effect as baseline EF decreased, with a 17% relative risk reduction for the PCE in patients with baseline EF = 33% (n =1,750; hazard ratio: 0.99; 95% confidence interval: 0.84 to 1.16; interaction as EF by quartiles, p = 0.013). The absolute reduction in the PCE increased with decreasing EF (EFCONCLUSIONS In heart failure patients with reduced EF, omecamtiv mecarbil produced greater therapeutic benefit as baseline EF decreased. These findings are consistent with the drug's mechanism of selectively improving systolic function and presents an important opportunity to improve the outcomes in a group of patients at greatest risk. Published by Elsevier on behalf of the American College of Cardiology Foundation.

KW - cardiovascular outcomes trial

KW - heart failure with reduced ejection fraction

KW - myotrope

KW - CARDIAC MYOSIN ACTIVATOR

KW - HEART-FAILURE

KW - INCREASE CONTRACTILITY

KW - DOUBLE-BLIND

KW - PHASE-2

U2 - 10.1016/j.jacc.2021.04.065

DO - 10.1016/j.jacc.2021.04.065

M3 - Journal article

C2 - 34015475

VL - 78

SP - 97

EP - 108

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

IS - 2

ER -