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Heart failure re-hospitalizations and subsequent fatal events in coronary artery disease: insights from COMMANDER-HF, EPHESUS, and EXAMINE

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Abstract

Background

Patients with coronary artery disease (CAD) are at increased risk of developing and being hospitalised for heart failure (HFH). However, the risk of HFH versus ischemic events may vary among patients with CAD, depending on whether acute myocardial infarction (MI), left ventricular dysfunction or decompensated HF is present at baseline.

Aims

We aim to explore the risk of non-fatal events (HFH, MI, stroke) and subsequent death in 3 landmark trials, COMMANDER-HF, EPHESUS and EXAMINE that, together, included patients with CAD with and without reduced ejection fraction and acute MI.

Methods

Events, person-time metrics and time-updated Cox models.

Results

In COMMANDER-HF the event-rate for the composite of AMI, stroke or all-cause death was 13.5 (12.8–14.3) events/100 py. Rates for AMI and stroke were much lower (2.2 [2.0–2.6] and 1.3 [1.1–1.6] events/100 py, respectively) than the rate of HFH (16.9 [16.1–17.9] events/100 py). In EPHESUS, the rates of MI and stroke were also lower than the rate of HFH: 7.2 (6.7–7.8), 1.9 (1.7–2.3), and 10.6 (9.9–11.3) events/100 py, but this was not true for EXAMINE with 4.4 (4.0–4.9), 0.7 (0.6–0.9), and 2.4 (2.0–2.7) events/100 py, respectively. In all 3 trials, a non-fatal event (HFH, MI or stroke) during follow-up doubled the risk of subsequent mortality. This most commonly followed a HFH.

Conclusions

A first or recurrent HFH is common in patients with CAD and AMI or HFrEF and indicates a poor prognosis. Preventing the development of heart failure after AMI and control of congestion in patients with CAD and HFrEF are key unmet needs and therapeutic targets.

Registration

ClinicalTrials.gov Identifier: NCT01877915. URL: https://clinicaltrials.gov/ct2/show/NCT01877915.

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Funding

The COMMANDER-HF trial was supported by Janssen Research and Development.

Author information

Authors and Affiliations

  1. Centre d’investigations Cliniques Plurithématique, Inserm 1433, Université de Lorraine, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu, CHRU Nancy–Hopitaux de Brabois, 4 rue du Morvan, 54500, Nancy, Vandoeuvre les Nancy, France

    João Pedro Ferreira & Faiez Zannad

  2. CHRU de Nancy, Inserm U1116, Nancy, France

    João Pedro Ferreira & Faiez Zannad

  3. FCRIN INI-CRCT, Nancy, France

    João Pedro Ferreira & Faiez Zannad

  4. Robertson Centre for Biostatistics and Clinical Trials, University of Glasgow, Glasgow, Scotland

    John G. Cleland

  5. National Heart Centre Singapore, Duke-National University of Singapore, Singapore, Singapore

    Carolyn S. P. Lam

  6. Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Carolyn S. P. Lam & Dirk J. van Veldhuisen

  7. Berlin–Brandenburg Center for Regenerative Therapies, Berlin, Germany

    Stefan D. Anker

  8. Department of Cardiology, German Center for Cardiovascular Research Partner Site Berlin, Charite Universitatsmedizin Berlin, Berlin, Germany

    Stefan D. Anker

  9. Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Mandeep R. Mehra

  10. Janssen Research and Development, Raritan, NJ, USA

    William M. Byra & David A. La Police

  11. Department of Medicine, University of Michigan School of Medicine, Ann Arbor, USA

    Bertram Pitt

  12. Cardiology Division, Department of Medicine, University of California, La Jolla, San Diego, USA

    Barry Greenberg

Authors
  1. João Pedro Ferreira
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  7. William M. Byra
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  8. David A. La Police
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  11. Faiez Zannad
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Corresponding authors

Correspondence to João Pedro Ferreira or Faiez Zannad.

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Conflict of interest

Dr Ferreira is a consultant for Boehringer-Ingelheim. Dr Zannad reports steering committee personal fees from Applied Therapeutics, Amgen, Bayer, Boehringer, Novartis, Janssen, Cellprothera and CVRx, advisory board personal fees from, AstraZeneca, Vifor Fresenius, Cardior, Cereno pharmaceutical, Corvidia, Merck, Myokardia, NovoNordisk and Owkin, stock options at Cereno and G3Pharmaceutical, and being the founder of the Global Cardiovascular Clinical Trialist Forum. Dr Lam has received research support from Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, and Vifor Pharma; has served as consultant or on the Advisory Board/ Steering Committee/ Executive Committee for Abbott Diagnostics, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Biofourmis, Boehringer Ingelheim, Boston Scientific, Corvia Medical, Cytokinetics, Darma Inc., Us2.ai, JanaCare, Janssen Research & Development LLC, Medtronic, Menarini Group, Merck, MyoKardia, Novartis, Novo Nordisk, Radcliffe Group Ltd., Roche Diagnostics, Sanofi, Stealth BioTherapeutics, The Corpus, Vifor Pharma and WebMD Global LLC; and serves as co-founder & non-executive director of Us2.ai. Dr Greenberg reports consulting fees from Amgen, Cytokinetics, EBR Systems, Impulse Dynamics, Ionis, Jaan, Janssen, Merck, Myokardia, Sanofi, Vifor, Viking, Windtree and Zensun. All the other authors report not having relevant conflicts of interest regarding the content of this manuscript.

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Ferreira, J.P., Cleland, J.G., Lam, C.S.P. et al. Heart failure re-hospitalizations and subsequent fatal events in coronary artery disease: insights from COMMANDER-HF, EPHESUS, and EXAMINE. Clin Res Cardiol 110, 1554–1563 (2021). https://doi.org/10.1007/s00392-021-01830-1

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  • DOI: https://doi.org/10.1007/s00392-021-01830-1

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