Tools for Practice

#93 ASA After Warfarin for Unprovoked VTE: Does the Little Clot-Fighter Make Sense?

When stopping oral anticoagulants (like warfarin) after treatment for venous thromboembolism (VTE), should ASA be offered?

Once patients have completed warfarin treatment for unprovoked VTE, low-dose ASA prevents recurrent VTE for one in 19 patients over 2 years with no increase in bleeding. ASA does not reduce VTE recurrence as effectively as oral anticoagulants, and does not replace them for the initial treatment of VTE.

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Two randomized controlled trials (WARFASA1 and ASPIRE2) of patients with 1st unprovoked VTE (deep vein thrombosis, pulmonary embolism, or both), most initially treated with warfarin for 6-12 months, then randomized to ASA 100 mg daily or placebo for ~2 years 
  • Pooled results3 for 1224 patients, mean age 57, 57% male: 
    • Statistically significant reduction in: 
      • VTE recurrence: ASA 13.1%, placebo 18.4%, number needed to treat (NNT)=19 
      • Major vascular events (VTE, myocardial infarction, stroke or cardiovascular death): ASA 14.8%, placebo 21.2%, NNT=16 
    • No difference in: 
      • Major bleeds: ASA 1.5%, placebo 1.2% 
      • Mortality: ASA 3.2%, placebo 3.8%.
  • Limitations: Protocol changes (WARFASA – likely to help find statistical difference), both trials stopped early due to poor recruitment (e.g. ASPIRE ‘aspired’ to recruit 3000 patients). 
  • Overall risk of recurrent VTE after warfarin treatment is ~7-11% in the 1st year4,5 
    • Risk remains elevated: ~15-20% at 3 years, 30% at 5 years 
    • Males and those with unprovoked VTE have ~2x higher recurrence risk than females or provoked VTE. 
  • While ASA reduces relative risk of recurrent VTE by 32%,1-3 warfarin and direct oral anticoagulants (DOACs), such as rivaroxabanreduce the risk by >80%.  
    • Anticoagulants (especially warfarin) increase major bleed risk by up to 2.5-fold.6,7 
  • Duration of therapy with warfarin or DOAC should be based on balancing VTE recurrence and bleed risk8 
    • ASA is not substitute for initial VTE treatment with warfarin or DOAC. 
updated aug 12 2016 by ricky

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  • G. Michael Allan MD CCFP
  • Jonathan Ference PharmD BCPS

1. Becattini C, Agnelli G, Schenone A, et al. N Engl J Med 2012;366:1959-67.

2. Brighton TA, Eikelboom JW, Mann K, et al. N Engl J Med 2012;367:1979-87.

3. Simes J, Becattini C, Agnelli G, et al. Circulation 2014;130:1062-71.

4. Douketis J, Tosetto A, Marcucci M, et al. BMJ 2011;342:d813.

5. Prandoni P, Noventa F, Ghirarduzzi A, et al. Haematologica 2007;92:199-205.

6. Castellucci LA, Cameron C, Le Gal G, et al. BMJ 2013;347:f5133.

7. Middeldorp S, Prins MH, Hutten BA. Cochrane Database Syst Rev 2014;8:CD001367.

8. Kearon C, Akl EA, Comerota AJ, et al. Chest 2012;141(2 Suppl):e419S-e494S.

Authors do not have any conflicts of interest to declare.