Angela Lowenstern, MD; Sana M. Al-Khatib, MD, MHS; Lauren Sharan, MD; Ranee Chatterjee, MD, MPH; Nancy M. Allen LaPointe, PharmD, MHS; Bimal Shah, MD, MBA; Ethan D. Borre, BA; Giselle Raitz, MD; Adam Goode, DPT, PhD; Roshini Yapa, MBBS; J. Kelly Davis, BA; Kathryn Lallinger, MSLS; Robyn Schmidt, BA; Andrzej S. Kosinski, PhD; Gillian D. Sanders, PhD
Disclaimer: The authors of this manuscript are responsible for its content. Statements in the manuscript should not be construed as endorsement by PCORI, AHRQ, or the U.S. Department of Health and Human Services. AHRQ retains a license to display, reproduce, and distribute the data and the report from which this manuscript was derived under the terms of the agency's contract with the author.
Acknowledgment: The authors thank Jamie Conklin, MSLIS, for help with the literature search and retrieval; Samantha E. Bowen, PhD, and Amanda J. McBroom, PhD, for assistance with project leadership; and Liz Wing, MA, for editorial assistance.
Grant Support: This project was funded under contract HHSA-290-2015-00004-I from AHRQ, U.S. Department of Health and Human Services.
Disclosures: Dr. Lowenstern, Al-Khatib, Sharan, Chatterjee, Allen LaPointe, Shah, Raitz, Goode, Yapa, Kosinski, Sanders, Mr. Borre, Mr. Davis, Ms. Lallinger, and Ms. Schmidt report support from AHRQ and PCORI through a contract with Duke University during the conduct of the study. Dr. Allen LaPointe is an employee of Premier. Mr. Shah reports personal fees from Medtronic, Premier, and Janssen and nonfinancial support from Boehringer Ingelheim, outside the submitted work. Disclosures can also be viewed at www.acponline.org/authors/icjme/ConflictOfInterestForms.do?msNum=M18-1523.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol: Available at www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42017069999. Statistical code: Available from Dr. Sanders (e-mail, email@example.com). Data set: See Supplement and full AHRQ report (available at www.effectivehealthcare.ahrq.gov).
Corresponding Author: Gillian D. Sanders, PhD, Duke Clinical Research Institute, 2400 Pratt Street, Durham, NC 27705; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Lowenstern, Sharan, and Raitz: 2400 Pratt Street, Duke Box 3850, Durham, NC 27710.
Dr. Al-Khatib: 7521 North Pavilion Building, Durham, NC 27715.
Dr. Chatterjee: 411 West Chapel Hill Street, Suite 500, Durham, NC 27701.
Dr. Allen LaPointe: 13034 Ballantyne Corporate Place, Charlotte, NC 28277.
Dr. Shah: 150 West Evelyn Avenue, Suite 150, Mountain View, CA 94041.
Mr. Borre, Ms. Lallinger, Ms. Schmidt, and Dr. Sanders: 2400 Pratt Street, Durham, NC 27705.
Dr. Goode: 2200 West Main Street, Durham, NC 27703.
Dr. Yapa: 12700 East 19th Avenue, Campus Box C281, Aurora, CO 80045.
Mr. Davis: 100 Fuqua Drive, A05G-1, Durham, NC 27708.
Dr. Kosinski: DCRI, Room 7058, P.O. Box 17969, Durham, NC 27715.
Author Contributions: Conception and design: S.M. Al-Khatib, N.M. Allen LaPointe, A. Goode, K. Lallinger, R. Schmidt, G.D. Sanders.
Analysis and interpretation of the data: A. Lowenstern, S.M. Al-Khatib, L. Sharan, R. Chatterjee, N.M. Allen LaPointe, B. Shah, E.D. Borre, G. Raitz, A. Goode, R. Yapa, J.K. Davis, A.S. Kosinski, G.D. Sanders.
Drafting of the article: A. Lowenstern, L. Sharan, R. Chatterjee, B. Shah, G. Raitz, A. Goode, K. Lallinger, G.D. Sanders.
Critical revision for important intellectual content: A. Lowenstern, S.M. Al-Khatib, R. Chatterjee, N.M. Allen LaPointe, B. Shah, A. Goode, K. Lallinger, R. Schmidt, A.S. Kosinski, G.D. Sanders.
Final approval of the article: A. Lowenstern, S.M. Al-Khatib, L. Sharan, R. Chatterjee, N.M. Allen LaPointe, B. Shah, E.D. Borre, G. Raitz, A. Goode, R. Yapa, J.K. Davis, K. Lallinger, R. Schmidt, A.S. Kosinski, G.D. Sanders.
Statistical expertise: A.S. Kosinski, G.D. Sanders.
Obtaining of funding: G.D. Sanders.
Administrative, technical, or logistic support: J.K. Davis, K. Lallinger, R. Schmidt.
Collection and assembly of data: A. Lowenstern, S.M. Al-Khatib, L. Sharan, R. Chatterjee, N.M. Allen LaPointe, E.D. Borre, G. Raitz, A. Goode, J.K. Davis, K. Lallinger, R. Schmidt, G.D. Sanders.
The comparative safety and effectiveness of treatments to prevent thromboembolic complications in atrial fibrillation (AF) remain uncertain.
To compare the effectiveness of medical and procedural therapies in preventing thromboembolic events and bleeding complications in adults with nonvalvular AF.
English-language studies in several databases from 1 January 2000 to 14 February 2018.
Two reviewers independently screened citations to identify comparative studies of treatments to prevent stroke in adults with nonvalvular AF who reported thromboembolic or bleeding complications.
Two reviewers independently abstracted data, assessed study quality and applicability, and rated strength of evidence.
Data from 220 articles were included. Dabigatran and apixaban were superior and rivaroxaban and edoxaban were similar to warfarin in preventing stroke or systemic embolism. Apixaban and edoxaban were superior and rivaroxaban and dabigatran were similar to warfarin in reducing the risk for major bleeding. Treatment effects with dabigatran were similar in patients with renal dysfunction (interaction P > 0.05), and patients younger than 75 years had lower bleeding rates with dabigatran (interaction P < 0.001). The benefit of treatment with apixaban was consistent in many subgroups, including those with renal impairment, diabetes, and prior stroke (interaction P > 0.05 for all). The greatest bleeding risk reduction was observed in patients with a glomerular filtration rate less than 50 mL/min/1.73 m2 (P = 0.003). Similar treatment effects were observed for rivaroxaban and edoxaban in patients with prior stroke, diabetes, or heart failure (interaction P > 0.05 for all).
Heterogeneous study populations, interventions, and outcomes.
The available direct-acting oral anticoagulants (DOACs) are at least as effective and safe as warfarin for patients with nonvalvular AF. The DOACs had similar benefits across several patient subgroups and seemed safe and efficacious for a wide range of patients with nonvalvular AF.
Patient-Centered Outcomes Research Institute. (PROSPERO: CRD42017069999)
AF = atrial fibrillation; DVT = deep venous thrombosis; KQ = key question; ICH = intracranial hemorrhage; PE = pulmonary embolism; TIA = transient ischemic attack.
Evidence search and selection.
AHRQ = Agency for Healthcare Research and Quality; KQ = key question; SR = systematic review.
* Articles/studies may be relevant to more than 1 KQ.
† 18 articles representing 9 studies provided additional outcome data that had not been included in our previous SR.
LAA = left atrial appendage; Obs = observational studies; RCT = randomized controlled trial; VKA = vitamin K antagonist.
Forest plots for comparison of Xa inhibitors versus warfarin (randomized controlled trials).
Outcomes examined. HR = hazard ratio.
Table 1. Outcomes of Interest in RCTs Evaluating Factor Xa Inhibitors (Apixaban, Rivaroxaban, or Edoxaban) Versus Warfarin
Table 2. Summary of SOE Ratings for Interventions Compared With Warfarin
no institutional affiliation
November 9, 2018
Overcoming afib by resolving sleep apnea
Afib, which can lead to stroke, is often a consequence of sleep apnea. Patients with afib should be sent for sleep apnea diagnosis and treatment. It may take up to six months for the afib to reverse following successful treatment of sleep apnea, along with the hypercoagulability that results from sleep apnea. During that time pharmaceutical products may be useful for stroke prevention, but probably will be unnecessary after the afib and hypercoagulability have resolved.
Lowenstern A, Al-Khatib SM, Sharan L, et al. Interventions for Preventing Thromboembolic Events in Patients With Atrial Fibrillation: A Systematic Review. Ann Intern Med. 2018;169:774–787. [Epub ahead of print 30 October 2018]. doi: https://doi.org/10.7326/M18-1523
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Published: Ann Intern Med. 2018;169(11):774-787.
Published at www.annals.org on 30 October 2018
Cardiology, Neurology, Rhythm Disorders and Devices, Stroke.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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