Author + information
- Received January 1, 2018
- Revision received April 17, 2018
- Accepted April 19, 2018
- Published online July 16, 2018.
- Ravi B. Patel, MDa,
- Ramkumar V. Venkateswaran, MDb,
- Abhayjit Singh, BAb,
- Deepak L. Bhatt, MD, MPHb,
- Gregg C. Fonarow, MDc,
- Rod Passman, MD, MSCEa,
- Javed Butler, MD, MPH, MBAd,
- Clyde W. Yancy, MD, MSca and
- Muthiah Vaduganathan, MD, MPHb,∗ ()
- aDivision of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
- bHeart and Vascular Center, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
- cDivision of Cardiology, University of California Los Angeles, Los Angeles, California
- dDepartment of Medicine, University of Mississippi, Jackson, Mississippi
- ↵∗Address for correspondence:
Dr. Muthiah Vaduganathan, Brigham and Women’s Hospital Heart and Vascular Center and Harvard Medical School, 75 Francis Street, Boston Massachusetts 02115.
Objectives This analysis sought to systematically characterize trial-level patterns in atrial fibrillation/atrial flutter (AF/AFL) by using the ClinicalTrials.gov database.
Background Despite an abundance of clinical trials in this field, there is a lack of high-level evidence guiding management of AF/AFL.
Methods We queried all closed, phase II to IV interventional trials registered in the ClinicalTrials.gov database through October 2016 that enrolled patients known to have AF/AFL. Published trials were evaluated for methodological quality, using the 3-item Jadad scale (range: 0 to 5, where 5 = highest quality).
Results The initial search yielded 465 uniquely registered studies, of which 348 directly studied AF/AFL. Of those studies, 173 (50%) were published, enrolling a median of 190 patients from a median of 15 sites. The volume of published trials increased over time (7% prior to 2008 vs. 41% from 2014 to 2016; p < 0.001 for trend). Of the completed trials, 29% remain unpublished. Industry sources accounted for most funding (54%). Recurrence of AF/AFL was the most common endpoint (45%), whereas rates of primary clinical endpoints were low (13%). The mean Jadad score of published trials of pharmacological approaches (n = 112) was 4.0 ± 1.4. Of the 61 AF/AFL trials involving ablation or device therapies, 69% were randomized, 28% were single-arm studies, and patient, proceduralist, and event-ascertainment blinding was used in 16%, 4%, and 44%, respectively.
Conclusions Contemporary trials of AF/AFL are often multicenter and modest in size. The primary study endpoint is commonly recurrence of arrhythmia, even in high-quality and late-phase trials. Although methodological quality is high in trials of pharmacologic approaches, trials of AF/AFL ablation and device therapies variably employ randomization and blinding.
Dr. Bhatt has served on advisory boards of Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, Regado Biosciences; and is on the board of directors of Boston VA Research Institute, Society of Cardiovascular Patient Care; Chair, American Heart Association Quality Oversight Committee; and is on the data monitoring committees of Cleveland Clinic, Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, Population Health Research Institute; and has received honoraria from American College of Cardiology (Senior Associate Editor, Clinical Trials and News), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor and Associate Editor), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees), Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); and has received research funding from Abbott, Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories, Ironwood, Ischemix, Lilly, Medtronic, Pfizer, Roche, Sanofi Aventis, The Medicines Company; and has received royalties from Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); and has served as site co-investigator for Biotronik, Boston Scientific, St. Jude Medical; and is a trustee of American College of Cardiology; and has received unfunded research support from FlowCo, PLx Pharma, and Takeda. Dr. Fonarow has relationships with, Novartis, Amgen, Bayer, Gambro, Medtronic, and Janssen; and holds the Eliot Corday Chair of Cardiovascular Medicine, UCLA, and is supported by the Ahmanson Foundation, Los Angeles, CA. Dr. Passman has received consulting/speaker fees for Medtronic and Biotronik; and royalties from UpToDate. Dr. Javed Butler has received research support from U.S. National Institutes of Health and European Union; and has consulted for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, CVRx, Janssen, Luitpold Pharmaceuticals, Medtronic, Merck, Novartis, Relypsa, Vifor Pharma, and ZS Pharma. Dr. Vaduganathan is supported by the U.S. National Heart Lung Blood Institute T32 postdoctoral training grant T32HL007604. All other authors have reported that they have no other relationships with industry relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- Received January 1, 2018.
- Revision received April 17, 2018.
- Accepted April 19, 2018.
- 2018 American College of Cardiology Foundation
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