The WARFASA trial, recently published in the NEJM, examined the role of aspirin after patients with VTE’s had completed 6-18 months of warfarin therapy. Given the safety of the treatment and the impressive reduction in VTE recurrence, it’s very likely that the results of the WARFASA trial will find their way into the next CHEST guideline updates.
Update 11/5/2012: The results of the ASPIRE trial have now been published. Read more about ASPIRE by clicking here.
Important Inclusion/Exclusion Criteria
- First episode of unprovoked symptomatic VTE (including proximal DVT or PE)
- “Unprovoked” (idiopathic) meaning there was no known risk factor for the VTE event.
- The trial, supplement, and protocol do not adequately describe what constitutes a risk factor worthy of exclusion from the trial. The protocol does mention exclusion for active cancer and women taking estro-progestin therapy.
- Multicenter, double-blind study in Italy
- Randomized to aspirin 100 mg daily or placebo for 2 years
- Primary efficacy endpoint: symptomatic VTE recurrence
- Primary safety endpoint: major bleeding (bleed in critical location, Hgb drop > 2, or RBC transfusion of > 2 units)
- Included 402 patients, nearly all were Caucasian, about 60% with an index case of DVT (40% PE), and most received warfarin for 6-12 months (about 10% with 18 months of therapy)
- Aspirin significantly reduced recurrent VTE (6.6% vs. 11.2%, p=0.02, HR 0.58, NNT 21)
- The risk of VTE recurrence was highest among male patients (HR 2.02, 95% CI 1.16 to 3.49) and those older than 65 years (HR 2.26, 95% CI 1.16 to 4.41)
- The duration of warfarin (>6 months vs. 6 months) was not shown to affect the risk of VTE recurrence (HR 1.21, 95% CI 0.73 to 1.99)
- There was no difference in major or minor bleeding (4 events in each arm) or mortality
Discussion and Conclusion
- The study excluded patients with risk factors for VTE, but the study protocol only excluded active cancer and estro-progestin therapy. There are a number of other risk factors (smoking, obesity, immobilization, trauma, surgery) that the trial protocol did not specify as exclusion criteria.
- The aspirin dose used (100 mg) is not readily available in the United States. Pharmacologically, 81 mg should have the same antiplatelet effect as a higher dose.
- The results of a similar trial (ASPIRE) are due to be published in 2012 have now been published (see this blog post), which included patients with a shorter duration of warfarin therapy (3-6 months, not longer than 12).
- With an extremely favorable safety profile and an impressive reduction in VTE recurrence, aspirin therapy should strongly be considered in patients completing a 6-12 month warfarin regimen for an idiopathic VTE.