Stephan Moll, MD writes… Well, it is not clear whether it does. A clinically relevant study (ASPIRE study) was published this week (Nov 22nd,2012) in the N Engl J Med [ref 1]. In patients who had a previous unprovoked (= idiopathic) DVT or PE and who had completed standard length (often considered to be 3-6 months) of warfarin therapy, aspirin did not prevent recurrent VTE. However aspirin was effective in preventing further thrombotic event (a conglomerate of arterial and venous events). Aspirin did not lead to an increase in risk of major bleeding. The findings are discrepant to the earlier WARFASA study, published in May 2012 in the N Engl J Med, which showed that Aspirin had efficacy in preventing recurrent VTE [ref 2]. The ASPIRE authors have also included a revealing, meta-analysis of this week’s study plus the previous WARFASA study [ref 2].
Background and Methods
There has been some evidence over the years that aspirin has some protective effective against venous thromboembolism (VTE; i.e. DVT and 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 randomized to receive either aspirin 100 mg /day or placebo 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 thrombosis-related complications together (DVT, PE, MI, stroke, or death due to heart or vascular problems – defined in conglomerate as “major vascular events”), the patients on aspirin had significantly less 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 significantly lower the risk of recurrence of DVT or PE, it did have a statistically significant benefit regarding the overall risk of major vascular events (arterial and venous event together). And aspirin did not increase the risk of major bleeding. It is not clear why the results of this larger ASPIRE study and of the previous WARFASA study are discrepant regarding aspirin’s benefit / lack of benefit on VTE revurrence.
This is now the second well-done study investigating the potential benefit of aspirin in patients who have had an unprovoked DVT or PE, with the previous one (WARFASA study) published in the N Engl J Med in May 2012 [ref 2] – results have been summarized and discussed on Clot Connect (link here). As both studies studied a similar patient population and were similarly designed, a meta-analysis of both studies was performed and included in this week’s N Engl J Med publication [ref 2]. This includes a total of 1,224 patients (616 on aspirin, 608 on placebo). The conglomerate data 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.
The summary conclusion of this meta-analysis: Aspirin is effective and safe in patients with previous unprovoked DVT or PE who have been treated with warfarin.
The findings of the two aspirin in VTE studies are noteworthy. It is not clear whether Aspirin can prevent DVTs and PEs in patients with history of unprovoked VTE, but aspirin is beneficial nonetheless, with no detectable increase in major bleeding risk. Consequences for my practice:
- In the patient with an unprovoked DVT or PE who has been treated with an anticoagulant (warfarin or Xarelto) for at least 3 months and in whom the anticoagulant is discontinued (because the risk of VTE recurrence is assessed to be low enough to stop anticoagulants or because the patient’s preference is not to be on an anticoagulant) I discuss with the patient to take long-term aspirin, rather than nothing.
- 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 now stop their anticoagulant and switch to aspirin instead? No. Warfarin and Xarelto are much more effective than aspirin. Aspirin is not a replacement for these anticoagulants. However, aspirin is better than nothing if the patient with unprovoked VTE has stopped anticoagulants.
- Would I recommend aspirin therapy in women who had a VTE associated with the 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, it is not known whether aspirin in these women is beneficial.
- ASPIRE study: Brighton TA et al. Low-dose aspirin for preventing the recurrent venous thromboembolism. N Engl J Med, Nov 22;367(21):1979-87.
- WARFASA study: Becattini C et al. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med 2012(May 24th);366:1959-1967.
Disclosures: I have consulted for Janssen.
Last updated: Jan 22nd, 2013