Derek K. Chu, MD, PhD; Christopher M. Hillis, MD, MSc; Darryl P. Leong, MBBS(Hons), MPH, MBiostat, PhD; Sonia S. Anand, MD, PhD; Deborah M. Siegal, MD, MSc
Acknowledgment: The authors thank Lois Cottrell and Jean Maragno, medical librarians at St. Joseph's Healthcare Hamilton, Charlton Campus, Hamilton, Ontario, Canada, for assistance with execution of the search strategy; Ms. Annie Duan for assistance with screening papers; Dr. Reed Siemieniuk for assistance with optimal information size calculations; and Dr. Gordon H. Guyatt for his methodological critique. The authors are grateful to all of the investigators who responded to requests for clarification of data.
Financial Support: This work was supported by a Regional Medical Associates scholarship to Dr. Chu. Dr. Leong is supported by the E.J. Moran Campbell Internal Career Award from McMaster University, the Heart and Stroke Foundation of Canada, and the Hamilton Health Sciences RFA Strategic Initiatives Program. Dr. Anand holds a Canadian Institutes of Health Research Tier 1 Chair in Ethnic Diversity and Cardiovascular Disease and a Heart and Stroke Foundation/Michael G. DeGroote Chair in Population Health Research. Dr. Siegal is supported by a Hamilton Health Sciences Early Career Award.
Disclosures: Dr. Chu reports a grant from Regional Medical Associates during the conduct of the study. Dr. Hillis reports a grant from Novartis Oncology and personal fees from Novartis Oncology, Bristol-Myers Squibb, and Celgene outside the submitted work. Dr. Leong reports personal fees from Janssen Pharmaceutical and Ferring Pharmaceuticals outside the submitted work. Dr. Siegal reports nonfinancial support from Bayer and personal fees from Bayer, Bristol-Myers Squibb/Pfizer, Servier, Portola Pharmaceuticals, and Novartis Pharmaceuticals outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-0284.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy 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: Registered at PROSPERO (CRD42015027051). Statistical code: metan varlist, where varlist contains events and nonevents in the treatment and nontreatment groups, respectively. Data set: Additional data from extracted studies are available from Dr. Siegal (e-mail, firstname.lastname@example.org).
Requests for Single Reprints: Deborah M. Siegal, MD, MSc, Population Health Research Institute, Department of Medicine, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada; e-mail, email@example.com.
Current Author Addresses: Dr. Chu: McMaster University Medical Centre, McMaster University, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada.
Dr. Hillis: Juravinski Cancer Centre, Hematology Department, McMaster University, Room 3-87, 699 Concession Street, Hamilton, Ontario L8P 1V4, Canada.
Drs. Leong, Anand, and Siegal: McMaster University, Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton General Hospital, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada.
Author Contributions: Conception and design: D.K. Chu, C.M. Hillis, S.S. Anand, D.M. Siegal.
Analysis and interpretation of the data: D.K. Chu, C.M. Hillis, D.P. Leong, S.S. Anand, D.M. Siegal.
Drafting of the article: D.K. Chu, D.P. Leong, D.M. Siegal.
Critical revision of the article for important intellectual content: D.K. Chu, C.M. Hillis, D.P. Leong, S.S. Anand, D.M. Siegal.
Final approval of the article: D.K. Chu, C.M. Hillis, D.P. Leong, S.S. Anand, D.M. Siegal.
Provision of study materials or patients: D.M. Siegal.
Statistical expertise: D.K. Chu, D.P. Leong, D.M. Siegal.
Obtaining of funding: D.K. Chu.
Administrative, technical, or logistic support: C.M. Hillis.
Collection and assembly of data: D.K. Chu, D.M. Siegal.
Patients with essential thrombocythemia (ET) are at high risk for both thrombosis and hemorrhage.
To evaluate the risks and benefits of antithrombotic therapy in adults with ET.
Multiple databases, including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, through 4 March 2017.
Randomized and observational studies of antiplatelet or anticoagulant therapy, published in any language and reporting thrombotic or hemorrhagic events.
Two reviewers independently extracted data, assessed risk of bias, and graded certainty of evidence.
No relevant randomized trials were identified. Twenty-four observational studies (18 comparative and 6 single-group) involving 6153 patients followed for 31 711 patient-years were reviewed; most were deemed to have high risk of bias. Most patients receiving antiplatelet therapy (3613 of 4527 [80%]) received low-dose aspirin (50 to 150 mg/d); 914 (20%) received high-dose aspirin (300 to 600 mg/d), dipyridamole, or other agents. Overall, findings were inconsistent and imprecise. The reported incidence rates of thrombosis, any bleeding, and major bleeding without antiplatelet therapy ranged from 5 to 110 (median, 20), from 3 to 39 (median, 8), and from 2 to 53 (median, 6) cases per 1000 patient-years, respectively. The reported relative risks for thrombosis, any bleeding, and major bleeding with antiplatelet therapy compared with none ranged from 0.26 to 3.48 (median, 0.74), from 0.48 to 11.04 (median, 1.95), and from 0.48 to 5.17 (median, 1.30), respectively. Certainty of evidence was rated low or very low for all outcomes.
No randomized trials, no extractable data on anticoagulants, lack of uniform bleeding definitions, and systematic reporting of outcomes.
Available evidence about the risk–benefit ratio of antiplatelet therapy in adults with ET is highly uncertain.
Regional Medical Associates. (PROSPERO: CRD42015027051)
Chu DK, Hillis CM, Leong DP, et al. Benefits and Risks of Antithrombotic Therapy in Essential Thrombocythemia: A Systematic Review. Ann Intern Med. 2017;167:170–180. [Epub ahead of print 27 June 2017]. doi: https://doi.org/10.7326/M17-0284
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Published: Ann Intern Med. 2017;167(3):170-180.
Published at www.annals.org on 27 June 2017
Coagulopathies, Hematology/Oncology, Platelet Disorders.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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