- Lana A Castellucci, thrombosis fellow1,
- Chris Cameron, PhD student2,
- Grégoire Le Gal, professor1,
- Marc A Rodger, professor1,
- Doug Coyle, professor3,
- Philip S Wells, professor1,
- Tammy Clifford, chief scientist4,
- Esteban Gandara, assistant professor1,
- George Wells, professor2,
- Marc Carrier, associate professor1
- 1Thrombosis Program, Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, ON, Canada K1H 8L6
- 2The University of Ottawa Heart Institute, Department of Community Medicine and Epidemiology, University of Ottawa, Canada
- 3Department of Community Medicine and Epidemiology, University of Ottawa, Canada
- 4Canadian Agency for Drugs and Technologies in Health, Ottawa, Canada
- Correspondence to: M Carrier
- Accepted 2 August 2013
Objective To summarise and compare the efficacy and safety of various oral anticoagulants (dabigatran, rivaroxaban, apixaban, and vitamin K antagonists) and antiplatelet agents (acetylsalicylic acid) for the secondary prevention of venous thromboembolism.
Design Systematic review and network meta-analysis.
Data sources Literature search using Medline (1950 to present), Embase (1980 to present), and the Cochrane Register of Controlled Trials using the OVID interface. Publications from potentially relevant journals were also searched by hand.
Review methods Randomised controlled trials of patients receiving anticoagulants, antiplatelet drugs, or placebo or observation for secondary prevention of venous thromboembolism. Selected outcomes were rates of recurrent venous thromboembolism and major bleeding. Two reviewers independently extracted data onto standardised forms.
Results 12 articles met our inclusion criteria, with 11 999 patients evaluated for efficacy and 12 167 for safety. All treatments reduced the risk of recurrent venous thromboembolism. Compared with placebo or observation, vitamin K antagonists at a standard adjusted dose (target international normalised ratio 2.0-3.0) showed the highest risk difference (odds ratio 0.07; 95% credible interval 0.03 to 0.15) and acetylsalicylic acid showed the lowest risk difference (0.65; 0.39 to 1.03). Risk of major bleeding was higher with a standard adjusted dose of vitamin K antagonists (5.24; 1.78 to 18.25) than with placebo or observation. Fatal recurrent venous thromboembolism and fatal bleeding were rare. Detailed subgroup and individual patient level data were not available.
Conclusions All oral anticoagulants and antiplatelet agents investigated in this analysis were associated with a reduced recurrence of venous thromboembolism compared with placebo or observation, although acetylsalicylic acid was associated with the lowest risk reduction. Vitamin K antagonists given at a standard adjusted dose was associated with the greatest risk reduction in recurrent venous thromboembolism, but also the greatest risk of major bleeding.
Contributors: LAC and CC contributed equally to this study. LAC conceived the study, performed the systematic review, data extraction, analysed the data, and drafted the manuscript. CC performed the data analysis and drafted the manuscript. GLG, EG, PSW, MAR, DC, TC, and GW analysed the data and reviewed the manuscript for important intellectual content. MC conceived the study, performed the systematic review, data extraction, and analysis, and drafted the manuscript. All authors had full access to the data and take responsibility for the integrity of the data and accuracy of the analysis. MC is guarantor.
Funding: The study did not receive specific funding. MC is a recipient of a New Investigator Award from the Heart and Stroke Foundation of Canada and holds a T2 research chair in cancer and thrombosis from the University of Ottawa. CC is a recipient of a Vanier Canada Graduate Scholarship from the Canadian Institutes of Health Research and has received funding from Canadian Network and Centre for Trials Internationally (CANNeCTIN). MAR is the recipient of a Career Scientist Award from the Heart and Stroke Foundation of Ontario. PSW is a recipient of a Canada research chair in venous thromboembolism.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; MC is a recipient of a New Investigator Award from the Heart and Stroke Foundation of Canada and holds a T2 research chair in cancer and thrombosis from the University of Ottawa; CC is a recipient of a Vanier CGS from the Canadian Institutes of Health Research and had received funding from CANNeCTIN; MAR is the recipient of a Career Scientist Award from the Heart and Stroke Foundation of Ontario; PSW is a recipient of a Canada research chair in venous thromboembolism; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: Not required.
Data sharing: No additional data available.
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