Cardiac resynchronization therapy in patients with a prior history of atrial fibrillation: Insights from four major clinical trials

Frederik Dalgaard; Marat Fudim; Sana M Al-Khatib; Daniel J Friedman; William T Abraham; John G F Cleland; Anne B Curtis; Michael R Gold; Valentina Kutyifa; Cecilia Linde; James Young; Fatima Ali-Ahmed; Anthony Tang; Antonio Olivas-Martinez; Lurdes Y T Inoue; Gillian D Sanders

doi:10.1111/jce.16022

Cardiac resynchronization therapy in patients with a prior history of atrial fibrillation: Insights from four major clinical trials

J Cardiovasc Electrophysiol. 2023 Sep;34(9):1914-1924. doi: 10.1111/jce.16022. Epub 2023 Jul 31.

Authors

Frederik Dalgaard^{1

2

3}, Marat Fudim^{1

4}, Sana M Al-Khatib^{1

4

5}, Daniel J Friedman^{1

4}, William T Abraham⁶, John G F Cleland⁷, Anne B Curtis⁸, Michael R Gold⁹, Valentina Kutyifa¹⁰, Cecilia Linde¹¹, James Young¹², Fatima Ali-Ahmed¹, Anthony Tang¹³, Antonio Olivas-Martinez¹⁴, Lurdes Y T Inoue¹⁴, Gillian D Sanders^{1

4

5

15

16

17}

Affiliations

¹ Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
² Department of Cardiology, Herlev and Gentofte Hospital, Copenhagen, Denmark.
³ Department of Medicine, Nykøbing Falster Sygehus, Nykøbing, Denmark.
⁴ Division of Cardiology, Duke University School of Medicine, Durham, North Carolina, USA.
⁵ Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
⁶ Division of Cardiovascular Medicine, The Ohio State University, Columbus, Ohio, USA.
⁷ National Heart and Lung Institute, Royal Brompton & Harefield Hospitals, Imperial College, London, UK.
⁸ Department of Medicine, University at Buffalo, Buffalo, New York, USA.
⁹ Medical University of South Carolina, Charleston, South Carolina, USA.
¹⁰ Division of Cardiology, Department of Medicine, University of Rochester Medical Center Rochester, Rochester, New York, USA.
¹¹ Department of Cardiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
¹² Cleveland Clinic, Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA.
¹³ Department of Medicine, Western University, Ontario, Canada.
¹⁴ Department of Biostatistics, University of Washington, Seattle, Washington, USA.
¹⁵ Duke-Margolis Center for Health Policy, Duke University, Durham, North Carolina, USA.
¹⁶ Evidence Synthesis Group, Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
¹⁷ Department of Population Health Sciences, Duke University School of Medicine, Durham, North Carolina, USA.

Abstract

Aims: To investigate the association of cardiac resynchronization therapy (CRT) on outcomes among participants with and without a history of atrial fibrillation (AF).

Methods: Individual-patient-data from four randomized trials investigating CRT-Defibrillators (COMPANION, MADIT-CRT, REVERSE) or CRT-Pacemakers (COMPANION, MIRACLE) were analyzed. Outcomes were time to a composite of heart failure hospitalization or all-cause mortality or to all-cause mortality alone. The association of CRT on outcomes for patients with and without a history of AF was assessed using a Bayesian-Weibull survival regression model adjusting for baseline characteristics.

Results: Of 3964 patients included, 586 (14.8%) had a history of AF; 2245 (66%) were randomized to CRT. Overall, CRT reduced the risk of the primary composite endpoint (hazard ratio [HR]: 0.69, 95% credible interval [CI]: 0.56-0.81). The effect was similar (posterior probability of no interaction = 0.26) in patients with (HR: 0.78, 95% CI: 0.55-1.10) and without a history of AF (HR: 0.67, 95% CI: 0.55-0.80). In these four trials, CRT did not reduce mortality overall (HR: 0.82, 95% CI: 0.66-1.01) without evidence of interaction (posterior probability of no interaction = 0.14) for patients with (HR: 1.09, 95% CI: 0.70-1.74) or without a history of AF (HR: 0.70, 95% CI: 0.60-0.97).

Conclusion: The association of CRT on the composite endpoint or mortality was not statistically different for patients with or without a history of AF, but this could reflect inadequate power. Our results call for trials to confirm the benefit of CRT recipients with a history of AF.

Keywords: CRT; atrial fibrillation; cardiac resynchronization therapy; heart failure; patient-level data; post hoc analysis; trial.

Publication types

Randomized Controlled Trial
Research Support, N.I.H., Extramural

MeSH terms

Atrial Fibrillation* / diagnosis
Atrial Fibrillation* / therapy
Bayes Theorem
Cardiac Resynchronization Therapy* / methods
Defibrillators, Implantable*
Heart Failure* / diagnosis
Heart Failure* / therapy
Humans
Treatment Outcome

Abstract

Publication types

MeSH terms

Grants and funding