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New-onset atrial fibrillation in patients with worsening heart failure and coronary artery disease: an analysis from the COMMANDER-HF trial

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Abstract

Background

Atrial fibrillation (AF) in the presence of heart failure (HF) is associated with poor outcomes including a high-risk of stroke and other thromboembolic events. Identifying patients without AF who are at high-risk of developing this arrhythmia has important clinical implications.

Aims

To develop a risk score to identify HF patients at high risk of developing AF.

Methods

The COMMANDER-HF trial enrolled 5022 patients with HF and a LVEF ≤ 40%, history of coronary artery disease, and absence of AF at baseline (confirmed with an electrocardiogram). Patients were randomized to either rivaroxaban (2.5 mg bid) or placebo. New-onset AF was confirmed by the investigator at study visits.

Results

241 (4.8%) patients developed AF during the follow-up (median 21 months). Older age (≥ 65 years), LVEF < 35%, history of PCI or CABG, White race, SBP < 110 mmHg, and higher BMI (≥ 25 kg/m2) were independently associated with risk of new-onset AF, whereas the use of DAPT was associated with a lower risk of new-onset AF. We then built a risk score from these variables (with good accuracy C-index = 0.71) and calibration across observed and predicted tertiles of risk. New-onset AF events rates increased steeply by increasing tertiles of the risk-score. Compared to tertile 1, the risk of new-onset AF was 2.5-fold higher in tertile 2, and 6.3-fold higher in tertile 3. Rivaroxaban had no effect in reducing new-onset AF. In time-updated models, new-onset AF was associated with a higher risk of subsequent all-cause death: HR (95%CI) 1.38 (1.11–1.73).

Conclusions

A well-calibrated risk-score identified patients at risk of new-onset AF in the COMMANDER-HF trial. Patients who developed AF had a higher risk of subsequent death.

Graphic abstract

Risk of new-onset atrial fibrillation in patients with HFrEF and coronary artery disease

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Acknowledgements

JF and FZ are supported by the RHU Fight-HF, a public grant overseen by the French National Research Agency (ANR) as part of the second “Investissements d’Avenir” program (reference: ANR-15-RHUS-0004), and by the French PIA project “Lorraine Université d’Excellence” (reference: ANR-15-IDEX-04-LUE).

Funding

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

Author information

Authors and Affiliations

  1. Centre D’Investigation Clinique 1433 Module Plurithématique, CHRU Nancy - Hopitaux de Brabois, CHRU de Nancy, FCRIN INI-CRCT, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu, Université de Lorraine, Nancy, France

    João Pedro Ferreira & Faiez Zannad

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

    John G. Cleland

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

    Carolyn S. P. Lam

  4. Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands

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

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

    Stefan D. Anker

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

    Stefan D. Anker

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

    Mandeep R. Mehra

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

    William M. Byra & David A. LaPolice

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

    Barry Greenberg

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  1. João Pedro Ferreira
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  2. John G. Cleland
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  9. Barry Greenberg
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  10. Faiez Zannad
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Correspondence to João Pedro Ferreira or Faiez Zannad.

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Ferreira, J.P., Cleland, J.G., Lam, C.S.P. et al. New-onset atrial fibrillation in patients with worsening heart failure and coronary artery disease: an analysis from the COMMANDER-HF trial. Clin Res Cardiol 111, 50–59 (2022). https://doi.org/10.1007/s00392-021-01891-2

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  • DOI: https://doi.org/10.1007/s00392-021-01891-2

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