Stephan Moll, MD writes… An important study (ASPIRE trial), relevant for patients with a history of DVT or PE, was published this week (Nov 22nd, 2012) in the New England Journal of Medicine [ref 1] . It showed that aspirin is not effective in preventing further DVT or PE in patients who have had a previous unprovoked (= idiopathic) DVT or PE and who have completed standard length (often considered to be 3-6 months) of blood thinner (warfarin) therapy. However, aspirin still had some benefit – it decreased the occurence of “vascular events” (i.e. a conglomerate of heart attacks, strokes, and DVT and PE when all were grouped together). Aspirin did not lead to an increase in risk of major bleeding.
Background and Methods
There has been some evidence over the years that aspirin has some protective effective against venous thromboembolism (also referred to as VTE – a term that includes deep vein thrombosis-DVT and pulmonary embolism-PE). However, aspirin’s protective effect has only been mild. The study published this week investigated patients with a history of unprovoked VTE. After patients had been treated routinely with warfarin (most had been treated for at least 3 months), they were enrolled and received either aspirin 100 mg /day or a placebo pill for up to 4 years. This was a double-blind study.
822 patients were enrolled: 411 received aspirin, 411 placebo. Median study period was 37.2 months. The findings:
- VTE (DVT or PE) recurred in 14 % of patients treated with aspirin (i.e. 1 of 7 patients), and in 18 % on placebo (i.e. 1 of 6 patients) during the slightly more than 3 years of follow-up. This means a recurrence rate of 4.8 % per year on aspirin vs. 6.5 % per year when not on aspirin. While this is a numerically lower risk or recurrence on aspirin, this difference was not statistically different.
- However, looking at all blood clot-related complications that could occur together (DVT, PE, heart attack, stroke, or death due to heart or vascular problems – called in conglomerate “major vascular events”), the patients on aspirin had significantly less such major vascular events: 5.2 % per year compared to 8.0 % per year in the placebo group.
- Major bleeding and clinically relevant non-major bleeding occurred was similar in both treatment groups.
While aspirin did not lower the risk of recurrence of DVT or PE, it did have a clear benefit regarding the overall risk of developing arterial clots (heart attack, stroke) and further vein clots (DVT and PE) or dying from vascular complications. And aspirin was safe – it did not increase the risk of major bleeding.
This is now the second well-done study investigating the potential benefit of aspirin in patients who have had an unprovoked DVT or PE. The previous one (called WARFASA study) was published in May 2012 [ref 2] and the results discussed on Clot Connect (link here). As both studies studied a similar patient population and were similarly designed, it is possible to do an analysis of both studies together (refered to as “meta-analysis”), which includes a total of 1,224 patients (616 on aspirin, 608 on placebo). The conglomerate data are also presented in this week’s N Engl J Med paper [ref 1] and show that aspirin:
- decreases the risk of recurrent DVT and PE
- decreases the risk of “major vascular events’ as defined above
- does not lead to an increase in major and clinically significant bleeding.
Thus, the summary conclusion from the meta-analysis: Aspirin is effective and safe in patients with previous unprovoked DVT or PE who have been treated with warfarin.
The findings of today’s study and of the May 2012 aspirin study show discrepant results: The WARFASA study showed benefit of aspirin in preventing recurrent VTE, today’s ASPIRE study showed no such benefit. Thus, it remains unclear whether aspirin can prevent DVTs and PEs. Consequences for my practice:
- If a patient has (a) had an unprovoked DVT or PE (i.e. one that came out of the blue and was not triggered by major surgery, hospitalization, major trauma, or estrogen therapy – contraceptive pill, patch or ring, or hormone replacement therapy) and (b) been treated with a blood thinner (warfarin, Xarelto ) for at least 3 months and (c) decided with his/her physician that he/she can come off blood thinners, then taking aspiring long-term once the blood thinner has been stopped is beneficial, preventing “vascular events”.; however, whetehr it is beneficial in preventing DVT and PE is not clear.
- What dose do I recommend? In the U.S., where the 100 mg tablet size studied in the two N Engl J Med studies is not available, I tell patients to take either a baby aspirin (81 mg) or an adult aspirin (325 mg) – typically I recommend the 81 mg size.
- Would I recommend that patients who are on long-term warfarin or Xarelto that they now stop their blood thinner and switch to aspirin instead? No. Clearly not. Warfarin and Xarelto are much more effective than aspirin. Aspirin is not a replacement for these blood thinners. But aspirin is better than nothing if the patient with unprovoked VTE has stopped blood thinners.
- Would I recommend aspirin therapy in women who had a VTE associated with contraceptive pill, ring, or patch and have now come off blood thinners? Yes. However, such women were not included in the two N Engl J Med studies. Thus, we don’t know whether aspirin in such women is beneficial in preventing further DVT or PE.
- Brighton TA et al. Low-dose aspirin for preventing the recurrent venous thromboembolism. N Engl J Med 2012(Nov 22);367(21):1979-87.
- Becattini C et al. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med 2012(May 24);366:1959-1967.
Disclosures: I have consulted for Janssen.
Last updated: Jan 22nd, 2013
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