Does acetyl salicylic acid (ASA) have a role in the prevention of venous thromboembolism? Ganesan Karthikeyan, 1,2 John W. Eikelboom, 2 Alexander G. G. Turpie 2 and Jack Hirsh 3 1 All India Institute of Medical Sciences, New Delhi, India, 2 Hamilton General Hospital, McMaster University, Hamilton, ON, and 3 Henderson Hospital Site, McMaster University, Hamilton, ON, Canada Summary Guidelines differ on whether acetyl salicylic acid (ASA, aspirin) should be used for prophylaxis in patients at high-risk of venous thromboembolism (VTE), principally because of differences in perceptions of its efficacy. ASA is an attractive therapeutic option because it is inexpensive, easy to administer and does not require monitoring. We critically reappraised the evidence from randomized controlled trials for the efficacy of ASA in VTE prevention. ASA is clearly efficacious in prevent- ing VTE compared to placebo or no treatment, but appears to be less efficacious than the low molecular weight heparins in small trials. There is little data for ASA in comparison with unfractionated heparin and warfarin. A large randomized controlled trial is required to clarify the role of ASA compared to contemporary anticoagulant strategies for the prevention of VTE. Keywords: acetyl salicylic acid, aspirin, deep venous throm- bosis, pulmonary thromboembolism, venous thromboembo- lism. Background The effectiveness of acetyl salicylic acid (ASA, aspirin) in the primary and secondary prevention of arterial thrombosis (Antiplatelet Trialists’ Collaboration (APTC) 2002, Lauer, 2002) is in keeping with the central role of platelet activation in the pathogenesis of arterial thrombosis (Davi & Patrono, 2007). Contribution of platelet activation to the development and progression of venous thrombosis is less certain and few clinical trials have tested the efficacy of ASA in the prevention of venous thromboembolism (VTE). The efficacy of anticoagulants (heparin and vitamin K antago- nists) for the prevention of venous thrombosis was estab- lished in the 1970’s and 1980’s and has been reinforced by more recent clinical trials with newer anticoagulants (Clagett & Reisch, 1988; Collins et al, 1988; Nurmohamed et al, 1992; Turpie et al, 2002). Early clinical trials with aspirin for the prevention of venous thrombosis were small and methodologically flawed, and the prevailing view was that the use of aspirin is not effective in preventing VTE. This notion was first seriously challenged by data from the APTC, which reported that ASA (and other antiplatelet therapies) produced impressive reductions in deep venous thrombosis (DVT) and pulmonary embolism (PE) (Antiplatelet Trialists’ Collaboration, 1994). Despite the results of the APTC analysis, ASA was not recommended for the prevention of VTE, either because it was not thought to be effective or because it was considered to be much less effective than anticoagulants. Although the results of the large pulmonary embolism prevention (PEP) trial reinforced the contention that ASA is effective for VTE prevention, (Rodgers et al, 2000) opinions regarding its efficacy remain divided as reflected by divergent guideline recommendations. The 2008 edition of the American College of Chest Physicians (ACCP) guidelines (Geerts et al, 2008) recommends against ASA for the prevention of VTE, likewise the UK National Institute for Health and Clinical Excellence (NICE) surgical throm- boprophylaxis guidelines do not consider ASA as an option for VTE prevention (NICE, 2007) whereas the American Association of Orthopedic Surgeons (AAOS) endorse ASA for prevention of pulmonary embolism (PE) in patients undergoing hip or knee replacement (AAOS, 2007, Haas et al, 2008). The use of ASA in VTE prevention is attractive because it is inexpensive, administered orally, does not require laboratory monitoring, and is associated with low bleeding rates. These advantages would, however, not justify its use if other methods of VTE prophylaxis were clearly superior to ASA. Given the divergent views expressed in the guidelines, we set out to critically reappraise the evidence for the efficacy of ASA in VTE prevention. We restricted our review to meta-analyses of randomized trials or individual randomized controlled trials enrolling at least 200 patients that evaluated the efficacy of ASA Correspondence: Dr Ganesan Karthikeyan MD, DM, Department of Medicine and Population Health Research Institute, Hamilton General Hospital, 237, Barton Street East, Hamilton, ON, Canada L8L 2X2 and Department of Cardiology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India – 110029. E-mail: karthik2010@gmail.com review First published online 12 May 2009 doi:10.1111/j.1365-2141.2009.07734.x ª 2009 Blackwell Publishing Ltd, British Journal of Haematology, 146, 142–149