CardioExchange Archive

It is unclear what the best approach is for the long-term treatment of people who have had a first unprovoked episode of venous thromboembolism (VTE). Although warfarin is effective at preventing a recurrence, it is inconvenient and raises the risk for bleeding. Newer anticoagulants have not been tested or approved for this population.

The ASPIRE (Aspirin to Prevent Recurrent Venous Thromboembolism) trial randomized 822 patients who had finished an initial course of anticoagulant therapy after a first unprovoked case of VTE to either aspirin (100 mg daily) or placebo for 4 years. Although the reduction in the rate for recurrent VTE with aspirin did not reach statistical significance, there were significant reductions in secondary outcomes of clinical events:

26% reduction in the yearly rate of VTE recurrence (primary endpoint):

• 6.5% for placebo and 4.8% for aspirin (HR 0.74, CI 0.52-1.05, p=0.09)

34% reduction in the yearly rate of major vascular events (VTE, MI, stroke, or CV death):

• 8.0% versus 5.2% (HR 0.66, CI 0.48-0.92, p=0.01)

33% reduction in the yearly rate of VTE, MI, stroke, major bleeding, or all-cause mortality (net clinical benefit):

• 9.0% versus 6.0% (HR 0.67, CI 0.49-0.91, p=0.01)

The ASPIRE investigators calculated that for every 1000 patients treated for 1 year, aspirin would prevent 17 episodes of VTE and 28 major thrombotic events, at a cost of 5 nonfatal bleeding episodes.

Reporting in the New England Journal of Medicine, the investigators write that although aspirin is “substantially less effective than warfarin,” it is “an attractive alternative because it is simple and inexpensive and its safety profile is well documented.”

In an accompanying editorial, Theodore Warkentin combined the ASPIRE results with findings from the recent WARFASA trial and calculated that aspirin results in a 32% reduction in the rate of recurrent VTE and a 34% reduction in the rate of major vascular events. He concludes that aspirin is “a reasonable option” for patients who wish to stop anticoagulation:

Aspirin is inexpensive, does not require monitoring (in contrast to warfarin), and does not accumulate in patients with renal insufficiency (in contrast to dabigatran and rivaroxaban); in addition, if major bleeding occurs or the patient requires urgent surgery, the antiplatelet effects of aspirin can be reversed…”