Background: Patients with idiopathic venous thromboembolism (VTE) are at particularly high risk of recurrence after oral anticoagulation is stopped. About 20 percent of such patients have a recurrence within two years. Extending anticoagulant therapy (e.g., warfarin [Coumadin]) can reduce the risk of a second VTE by up to 64 percent, but it requires ongoing monitoring and dose adjustments, and is beneficial only while therapy continues. However, preliminary evidence suggests that aspirin may also be useful in the secondary prevention of VTE. Becattini and colleagues conducted a double-blind clinical trial examining whether aspirin could be used to prevent recurrent VTE.
The Study: Eligible participants were adults who had been taking anticoagulants for six to 18 months for a first-time, symptomatic, unprovoked proximal deep venous thrombosis (DVT), pulmonary embolism, or both. Patients were randomized to receive placebo or 100 mg of aspirin daily for two years, beginning within two weeks of discontinuing anticoagulation therapy. The primary efficacy outcome was the symptomatic recurrence of DVT or pulmonary embolism. The primary safety outcome was the occurrence of a major bleeding episode, defined as bleeding occurring in a critical location (e.g., intracranial, intraspinal, intraarticular), requiring transfusion, or associated with death.
Results: Over the course of the study, 205 patients received aspirin and 197 received placebo. Baseline characteristics were comparable between the two groups. Significantly fewer patients had a recurrence of DVT or pulmonary embolism while using aspirin compared with patients in the placebo group (5.9 versus 11.0 percent per year; hazard ratio = 0.55; P = .02). Both groups had a similar likelihood of major bleeding events, with a rate of about 0.3 percent per patient-year. One episode of nonfatal major bleeding and three episodes of clinically relevant nonmajor bleeding occurred in each group. Overall, mortality rates were similar (1.4 percent per year in the aspirin group versus 1.3 percent per year in the placebo group), with one patient in each group dying from pulmonary embolism.
Conclusion: Among patients with an initial unprovoked VTE who received six to 18 months of oral anticoagulation therapy, the subsequent daily use of aspirin significantly reduced the rate of recurrent VTE compared with placebo, with no increase in the risk of major bleeding.