AHA: Aspirin’s latest laurel: Preventing recurrent venous thromboembolism

Evidence is tipping in favor of aspirin for long-term prevention of recurrent venous thromboembolism in high-risk patients. While the ASPIRE trial found no significant reduction in the rate of late recurrence in patients who had a first episode of unprovoked venous thromboembolism, its results, combined with those of the WARFARA study, underscore aspirin’s numerous benefits.

The results were published online Nov. 4 in the New England Journal of Medicine and simultaneously presented as a late-breaking clinical trial at the 2012 American Heart Association’s scientific sessions in Los Angeles.

Initial treatment of patients who experience a first episode of unprovoked venous thromboembolism typically includes use of an anticoagulant to reduce the high risk of early recurrence. Treatment may be extended using vitamin K antagonists such as warfarin to prevent late recurrence, but the approach also has bleeding risks and is inconvenient. Some patients choose to discontinue anticoagulation after three to six months, although their risk of late recurrence remains high.

“In this context, aspirin, although substantially less effective than warfarin, provides an attractive alternative because it is simple and inexpensive and its safety profile is well documented,” wrote Timothy A. Brighton, MB, of Prince of Wales Hospital in Sydney, Australia, and colleagues. “Patients who have had a first unprovoked event of venous thromboembolism appear to be at greater risk of arterial thrombosis and cardiovascular death, and an added appeal of aspirin is that it has been associated with an overall reduction in the risk of major thrombotic events (arterial and venous) and cardiovascular death.”

The researchers designed ASPIRE (Aspirin to Prevent Recurrent Venous Thromboembolism) to evaluate the efficacy of low-dose aspirin to prevent recurrent venous thromboembolism in patients who had a first episode of unprovoked venous thromboembolism. The double-blind, randomized trial compared 100 mg daily dose of aspirin to placebo for up to four years in 822 patients who completed initial anticoagulation therapy. The study period spanned 2003 to 2011, with a median follow-up period of 37.2 months.

The primary outcome was recurrence of venous thromboembolism. Secondary outcomes were major vascular events and net clinical benefit. The primary safety outcome was bleeding (major or clinically relevant nonbleeding).

Their results showed a venous thromboembolism recurrence rate of 6.5 percent a year in the aspirin group (411 patients) vs. 4.8 percent a year in the placebo group (411 patients), which was not a significant reduction.

But for secondary composite outcomes, they reported an event rate of 5.2 percent per year for venous thromboembolism, MI, stroke or cardiovascular death in the aspirin group vs. 8 percent in the placebo group; and an event rate of 6 percent a year for venous thromboembolism, MI, stroke or death from any cause in the aspirin group vs. 9 percent in the placebo group. That translated into reductions in secondary outcomes of 34 percent and 33 percent, respectively.

Rate of bleeding did not differ significantly between groups.

Brighton et al explained that ASPIRE failed to recruit its target number of patients and consequently was underpowered to show significant differences in the recurrence of venous thromboembolism. But their results were consistent with those of a similar study called WARFASA (the Warfarin and Aspirin study). “The combined results of the WARFASA and ASPIRE trials show a highly significant reduction of 32 percent in the rate of recurrence of venous thromboembolism and a reduction of 34 percent in the rate of major vascular events with no excess of bleeding,” they wrote.

They calculated that, based on ASPIRE results, the use of aspirin in the long-term prevention of recurrent venous thromboembolism was expected to lead to 17 fewer recurrent venous thromboembolism events and 28 fewer major thrombotic events per year per every 1,000 patients. On the flip side, the therapy was expected to result in five nonfatal bleeding incidents.

“Thus, aspirin is an attractive option for such patients once they have completed an initial course of anticoagulation therapy,” they concluded.

In an accompanying editorial, Theodore E. Warkentin, MD, of the DeGroote School of Medicine at McMaster University in Hamilton, Canada, described aspirin as “a reasonable option” but he emphasized that patients who had a first episode of unprovoked venous thromboembolism be treated with an anticoagulant for at least three months before switching to aspirin.

Among aspirin’s advantages, Warkentin wrote: “Aspirin is inexpensive, does not require monitoring (in contrast to warfarin), and does not accumulate in patients with renal insufficiency (in contrast to dabigatran [Pradaxa, Boehringer Ingelheim] and rivaroxaban [Xarelto, Janssen Pharmaceuticals]; in addition, if major bleeding occurs or the patient requires urgent surgery, the antiplatelet effects of aspirin can be reversed with transfusion of platelets.”