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KCCQ total symptom score, clinical outcome measures, and adverse events associated with omecamtiv mecarbil for heart failure with reduced ejection fraction: a systematic review and meta-analysis of randomized controlled trials

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Abstract

Background

Omecamtiv mecarbil (OM) is a direct myosin activator that augments left ventricular systolic function. This review compares OM to placebo by evaluating its effect on clinical outcomes and adverse events in patients with heart failure with reduced left ventricular ejection fraction.

Methods and results

A literature search of multiple databases for randomized controlled trials (RCTs) investigating OM versus placebo was undertaken. Six RCTs comprising 9596 patients were included. Use of OM was associated with a reduced risk of stroke (RR: 0.69; 95% CI 0.52–0.92). There was no significant mean difference (MD) change in the KCCQ total symptom score (MD: 1.82, 95% CI − 1.33 to 4.97), all-cause death (RR: 1.00; 95% CI 0.93–1.07), hospital readmissions (RR: 0.96; 95% CI 0.90–1.03), myocardial infarction (RR: 1.05; 95% CI 0.83–1.33), cardiovascular death (RR: 1.01; 95% CI 0.92–1.10), heart failure (HF) events (RR: 0.95; 95% CI 0.89–1.02), or a composite of cardiovascular death or HF events (RR: 0.97; 95% CI 0.93–1.02). In addition, OM was associated with an increased risk of dizziness (RR: 1.25; 95% CI 1.04–1.50) and hypotension (RR: 1.17; 95% CI 1.01–1.36). Other adverse events including ventricular tachyarrhythmias, (RR: 0.95; 95% CI 0.82–1.11), supraventricular tachyarrhythmias and atrial fibrillation/flutter (RR: 0.73; 95% CI 0.46–1.18), dyspnea (RR: 1.00; 95% CI 0.86–1.18), and acute renal injury (RR: 0.88; 95% CI 0.60–1.27) were not significant.

Conclusion

OM is generally well tolerated. We identified a reduced risk of stroke with use of OM. However, there was no improvement in other clinical outcomes or quality of life.

Study protocol was registered in PROSPERO international prospective register of systematic reviews (CRD42022348423).

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Data availability

All data used in our meta-analyses are publicly available and de-identified within each individual trial.

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Medicine, Banner University Medical Center-University of Arizona, 1501 N. Campbell Ave, Tucson, AZ, 85724, USA

    Ramzi Ibrahim, Chelsea Takamatsu & George Khludenev

  2. Department of Medicine, Creighton University School of Medicine-Phoenix, AZ 350 W. Thomas Road, Phoenix, AZ, 85013, USA

    Abdulbaril Olagunju

  3. University of Arizona College of Medicine, 1501 N. Campbell Ave, Tucson, AZ, 85724, USA

    Ramzi Ibrahim, Kristina Terrani, Chelsea Takamatsu & George Khludenev

  4. Department of Cardiovascular Medicine, Heart, Vascular, and Thoracic Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, 44195, USA

    Preethi William

Authors
  1. Ramzi Ibrahim
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  2. Abdulbaril Olagunju
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  3. Kristina Terrani
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  4. Chelsea Takamatsu
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  5. George Khludenev
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  6. Preethi William
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Correspondence to Ramzi Ibrahim.

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Ibrahim, R., Olagunju, A., Terrani, K. et al. KCCQ total symptom score, clinical outcome measures, and adverse events associated with omecamtiv mecarbil for heart failure with reduced ejection fraction: a systematic review and meta-analysis of randomized controlled trials. Clin Res Cardiol 112, 1067–1076 (2023). https://doi.org/10.1007/s00392-023-02172-w

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  • DOI: https://doi.org/10.1007/s00392-023-02172-w

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