Effects of omecamtiv mecarbil in heart failure with reduced ejection fraction according to blood pressure: the GALACTIC-HF trial.

Aim: Patients with heart failure with reduced ejection fraction and low systolic blood pressure (SBP) have high mortality, hospitalizations, and poorly tolerate evidence-based medical treatment. Omecamtiv mecarbil may be particularly helpful in such patients. This study examined its efficacy and tolerability in patients with SBP ≤100 mmHg enrolled in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF).
Methods and Results: The GALACTIC-HF enrolled patients with baseline SBP ≥85 mmHg with a primary outcome of time to cardiovascular death or first heart failure event. In this analysis, patients were divided according to their baseline SBP (≤100 vs. >100 mmHg). Among the 8232 analysed patients, 1473 (17.9%) had baseline SBP ≤100 mmHg and 6759 (82.1%) had SBP >100 mmHg. The primary outcome occurred in 715 (48.5%) and 2415 (35.7%) patients with SBP ≤100 and >100 mmHg, respectively. Patients with lower SBP were at higher risk of adverse outcomes. Omecamtiv mecarbil, compared with placebo, appeared to be more effective in reducing the primary composite endpoint in patients with SBP ≤100 mmHg [hazard ratio (HR), 0.81; 95% confidence interval (CI), 0.70-0.94] compared with those with SBP >100 mmHg (HR, 0.95; 95% CI, 0.88-1.03; P-value for interaction = 0.051). In both groups, omecamtiv mecarbil did not change SBP values over time and did not increase the risk of adverse events, when compared with placebo.
Conclusion: In GALACTIC-HF, risk reduction of heart failure outcomes with omecamtiv mecarbil compared with placebo was large and significant in patients with low SBP. Omecamtiv mecarbil did not affect SBP and was well tolerated independent of SBP values.
Competing Interests: Conflict of interest: M.M. has received funding to his institution from Amgen and Cytokinetics as participant to the Executive Committee during the trial and for patients’ enrolment; has received consulting fees for participation to advisory boards from AstraZeneca, Bayer, and Boehringer Ingelheim; has received personal fees as member of Executive or Data Monitoring Committees of sponsored clinical trials from LivaNova and Vifor Pharma; has received speaker fees from Abbott Vascular and Edwards Therapeutics for speeches at sponsored meetings; and has participated on Data Safety Monitoring boards for Actelion. B.L.C. has received consulting fees from Amgen, Cardurion, Corvia, Myokardia, and Novartis. R.D. has received research grants and other payment or honoraria from Amgen. G.M.F. has received grant funding to his institution from American Heart Association, Amgen, Bayer, Bristol Myers Squibb, CSL-Behring, Cytokinetics, Merck, Myokardia, and National Institutes of Health; has received consulting fees from Abbott, American Regent, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cardionomic, Cytokinetics, Medtronic, Myovant, Novartis, Reprieve, Sequana, Windtree Therapeutics, and WhiteSwell; and has participated on Data Safety Monitoring boards or advisory boards for EBR Systems, LivaNova, Medtronic, Siemens, Rocket Pharma, and V-Wave. J.J.V.M. has received funding to his institution from Amgen and Cytokinetics for his participation in the Steering Committee for the ATOMIC-HF, COSMIC-HF, and GALACTIC-HF trials and meetings and other activities related to these trials; has received personal fees from Abbott, Alkem Metabolics, Eris Lifesciences, Hikma, Lupin, Medscape/Heart.Org, ProAdWise Communications, Radcliffe Cardiology, Servier, Sun Pharmaceuticals, and The Corpus; and has received funding paid to his institution for activities related to trials or other activities from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardurion, DalCor, GlaxoSmithKline, Ionis Pharmaceuticals, KBP Biosciences, Novartis, and Theracos. S.D.S. has received grant funding to his institution from Actelion, Alnylam, Amgen, AstraZeneca, Bayer, Bellerophon, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis Pharmaceuticals, Lilly, Mesoblast, MyoKardia, National Institutes of Health/National Heart, Lung, and Blood Institute, Neurotronik, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, US2.AI; and has received consulting fees from Abbott, Action, Akros, Alnylam, American Regent, Amgen, Anacardio, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardiac Dimensions, Cardior, Cardurion, CellProthera, Corvia, Cytokinetics, Daiichi Sankyo, Dinaqor, GlaxoSmithKline, Janssen, Lexicon, Lilly, Merck, Moderna, Myokardia, Novartis, Puretech Health, Quantum Genomics, Roche, Sanofi Pasteur, Sarepta, Tenaya, Theracos, and Tremeau. D.B. has received research grants from Abbott, Bayer, Boehringer Ingelheim, Novartis, Pfizer, SOBI, and Zoll; has received consulting fees from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Ionis Pharmaceuticals, Novartis, Novo Nordisk, Pfizer, SOBI, and Zoll; has received speaker fees or honoraria and support for attending meetings and/or travels from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Ionis Pharmaceuticals, MSD, Novartis, Pfizer, SOBI, and Zoll; and is in the European Society of Cardiology Working Group on Pulmonary Circulation and Right Ventricular Function. J.C.F. has served on the Board of Directors for the Heart Failure Society of America. C.F. has received personal fees for consulting from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Servier, and Vifor Pharma; has received honoraria for lectures and educational events from AstraZeneca, Bayer, Boehringer Ingelheim, Servier, and Vifor Pharma; has received honoraria for lectures from Novartis; has received support for attending meetings and/or travel from Bayer, Servier, and Vifor Pharma; has participated on advisory boards for Bayer, Boehringer Ingelheim, Novartis, and Vifor Pharma; and has received grants for medical writing from Merck Serono and Roche. E.G. has received consulting fees from AOP Orphan Pharmaceuticals, Bayer, Boehringer Ingelheim, Novartis, and Servier; has received personal fees from Bayer, Boehringer Ingelheim, Janssen Pharmaceuticals, Novartis, Pfizer, and Servier; and is the President of the Slovak Society of Cardiology. J.G.H. has received grants and consulting fees from Amgen, AstraZeneca, Boehringer Ingelheim, Novartis, Novo Nordisk, and Pfizer; has received personal fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Novo Nordisk, and Pfizer; and is Co-Chair of the Heart Failure Pathway Group of the Province of Alberta, Heart Failure lead at University of Calgary, and in the Canadian Cardiovascular Society Guidelines and Development Committees. J.L. has received research agreements from Amgen during the conduct of the study through the National Center for Cardiovascular Diseases. E.O. has received support to her institution (Montreal Heart Institute) for being local Principal Investigator and member of the Steering Committee of the GALACTIC-HF trial from Amgen and Cytokinetics; has received grant funding to her institution (Montreal Heart Institute) for clinical trials from AstraZeneca, American Regent, Cardurion, and Canadian Institutes of Health Research (CIHR); has received consulting fees from AstraZeneca, Bayer, Cytokinetics, Boehringer Ingelheim, Eli Lilly, and Janssen; has received speaker fees or other honoraria from AstraZeneca, Bayer, and Boehringer Ingelheim; and has participated on Data Safety Monitoring boards or advisory boards for Bayer, Boehringer Ingelheim, and the independent COLpEF trial. S.A.A. is an employee and shareholder of Amgen. S.B.H., S.K., and F.I.M. are employees and shareholders of Cytokinetics. J.R.T. has received personal fees as Chairperson of the GALACTIC-HF Executive Committee from Amgen and Cytokinetics; has received personal fees for research contracts and/or consulting fees from 3ive Labs, Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardurion, Medtronic, Merck, Novartis, Verily, ViCardia, and Windtree Therapeutics; has served as Secretary and Treasurer of Heart Failure Society of America; and is currently President-Elect of the Heart Failure Society of America. The other authors have no conflicts of interest to disclose.
(© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.)