[Skip to Navigation]
Original Investigation
October 13, 2021

Assessment of Omecamtiv Mecarbil for the Treatment of Patients With Severe Heart Failure: A Post Hoc Analysis of Data From the GALACTIC-HF Randomized Clinical Trial

Author Affiliations
  • 1Division of Cardiology, Duke University School of Medicine, Durham, North Carolina
  • 2Duke Clinical Research Institute, Durham, North Carolina
  • 3Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
  • 4Instituto Cardiovascular de Rosario, Estudios Clínicos Latino América, Rosario, Argentina
  • 5Cardiovascular Research Centre, British Heart Foundation, Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom
  • 6Department of Medical and Surgical Specialties, University of Brescia, Brescia, Italy
  • 7Division of Cardiovascular Medicine, University of Minnesota, Minneapolis
  • 8Division of Cardiology, Universidad da Coruña, A Coruña, Galicia, Spain
  • 9Department of Cardiology, Linköping University Hospital, Linköping, Sweden
  • 10Department of Cardiology, Odd. Srdcovehozlyhavania a Transplantacie, Bratislava, Slovakia
  • 11Division of Cardiology, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, Canada
  • 12Heart Transplant Unit, St. Vincent’s Hospital Sydney, Darlinghurst, NSW, Australia
  • 13Emergency Cardiology Department, Ukranian Strazhesko Institute of Cardiology, Kiev, Ukraine
  • 14Cardiology Department, St. John of God Hospital, Budapest, Hungary
  • 15Amgen, Inc, Thousand Oaks, California
  • 16Clinical Research, Cytokinetics, South San Francisco, California
  • 17Research and Development, Cytokinetics, South San Francisco, California
  • 18Division of Cardiology, San Francisco VA Medical Center, San Francisco, California
  • 19Division of Cardiology, University of California San Francisco, San Francisco
JAMA Cardiol. 2022;7(1):26-34. doi:10.1001/jamacardio.2021.4027
Key Points

Question  What are the efficacy and safety of omecamtiv mecarbil for the treatment of patients with severe heart failure (HF)?

Finding  In this post hoc analysis of data from 8232 patients with symptomatic HF enrolled in the Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) randomized clinical trial, patients with severe HF benefited from treatment with omecamtiv mecarbil for the primary end point of time to first HF event or death from cardiovascular causes, whereas patients without severe HF experienced no significant treatment benefit. Omecamtiv mecarbil therapy was well tolerated with regard to changes in blood pressure, kidney function, and potassium level, even among patients with severe HF.

Meaning  The findings of this post hoc analysis support a potential role of omecamtiv mecarbil in the treatment of patients with severe HF.

Abstract

Importance  Heart failure with reduced ejection fraction is a progressive clinical syndrome, and many patients’ condition worsen over time despite treatment. Patients with more severe disease are often intolerant of available medical therapies.

Objective  To evaluate the efficacy and safety of omecamtiv mecarbil for the treatment of patients with severe heart failure (HF) enrolled in the Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) randomized clinical trial.

Design, Setting, and Participants  The GALACTIC-HF study was a global double-blind, placebo-controlled phase 3 randomized clinical trial that was conducted at multiple centers between January 2017 and August 2020. A total of 8232 patients with symptomatic HF (defined as New York Heart Association symptom class II-IV) and left ventricular ejection fraction of 35% or less were randomized to receive omecamtiv mecarbil or placebo and followed up for a median of 21.8 months (range, 15.4-28.6 months). The current post hoc analysis evaluated the efficacy and safety of omecamtiv mecarbil therapy among patients classified as having severe HF compared with patients without severe HF. Severe HF was defined as the presence of all of the following criteria: New York Heart Association symptom class III to IV, left ventricular ejection fraction of 30% or less, and hospitalization for HF within the previous 6 months.

Interventions  Participants were randomized at a 1:1 ratio to receive either omecamtiv mecarbil or placebo.

Main Outcomes and Measures  The primary end point was time to first HF event or cardiovascular (CV) death. Secondary end points included time to CV death and safety and tolerability.

Results  Among 8232 patients enrolled in the GALACTIC-HF clinical trial, 2258 patients (27.4%; mean [SD] age, 64.5 [11.6] years; 1781 men [78.9%]) met the specified criteria for severe HF. Of those, 1106 patients were randomized to the omecamtiv mecarbil group and 1152 to the placebo group. Patients with severe HF who received omecamtiv mecarbil experienced a significant treatment benefit for the primary end point (hazard ratio [HR], 0.80; 95% CI, 0.71-0.90), whereas patients without severe HF had no significant treatment benefit (HR, 0.99; 95% CI, 0.91-1.08; P = .005 for interaction). For CV death, the results were similar (HR for patients with vs without severe HF: 0.88 [95% CI, 0.75-1.03] vs 1.10 [95% CI, 0.97-1.25]; P = .03 for interaction). Omecamtiv mecarbil therapy was well tolerated in patients with severe HF, with no significant changes in blood pressure, kidney function, or potassium level compared with placebo.

Conclusions and Relevance  In this post hoc analysis of data from the GALACTIC-HF clinical trial, omecamtiv mecarbil therapy may have provided a clinically meaningful reduction in the composite end point of time to first HF event or CV death among patients with severe HF. These data support a potential role of omecamtiv mecarbil therapy among patients for whom current treatment options are limited.

Trial Registration  ClinicalTrials.gov Identifier: NCT02929329

Add or change institution
Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    ×