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 V
AU - Metra, Marco
AU - Solomon, Scott D
AU - Biering-Sørensen, Tor
AU - Böhm, 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 I
AU - GALACTIC-HF Investigators
N1 - Published by Elsevier Inc.
PY - 2021/7/13
Y1 - 2021/7/13
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) (≤35%).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 (≤22%) compared with the highest 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 ≤22% (n = 2,246; hazard ratio: 0.83; 95% confidence interval: 0.73 to 0.95) compared with patients with 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 (EF ≤22%; absolute risk reduction, 7.4 events per 100 patient-years; number needed to treat for 3 years = 11.8), compared with no reduction in the highest EF quartile.CONCLUSIONS: 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. (Registrational Study With Omecamtiv Mecarbil/AMG 423 to Treat Chronic Heart Failure With Reduced Ejection Fraction [GALACTIC-HF]; NCT02929329).
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) (≤35%).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 (≤22%) compared with the highest 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 ≤22% (n = 2,246; hazard ratio: 0.83; 95% confidence interval: 0.73 to 0.95) compared with patients with 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 (EF ≤22%; absolute risk reduction, 7.4 events per 100 patient-years; number needed to treat for 3 years = 11.8), compared with no reduction in the highest EF quartile.CONCLUSIONS: 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. (Registrational Study With Omecamtiv Mecarbil/AMG 423 to Treat Chronic Heart Failure With Reduced Ejection Fraction [GALACTIC-HF]; NCT02929329).
UR - http://www.scopus.com/inward/record.url?scp=85108632650&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2021.04.065
DO - 10.1016/j.jacc.2021.04.065
M3 - Journal article
C2 - 34015475
SN - 0735-1097
VL - 78
SP - 97
EP - 108
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 2
ER -