Patients with unprovoked venous thromboembolism are at long-term risk for recurrence after discontination of oral anticoagulant treatment. Two years after treatment is withdrawn, the risk of recurrrence is about 20%. Although extending anticoagulant therapy reduces the recurrence risk, it is associated with increased bleeding. Aspirin therapy is effective in the primary prevention of venous thromboembolism, with risk reduction ranging from 20% to 50%. The possible benefit of aspirin for the prevention of recurrent venous thromboembolism is unknown.
The aim of this multicenter, investigator-initiated, double-blind trial was to determine the clinical benefit of aspirin therapy for preventing recurrence in patients with unprovoked venous thromboembolism following a course of treatment with vitamin K antagonists. Subjects were patients older than 18 years who had completed 6 to 18 months of anticoagulant treatment for first-ever unprovoked venous thromboembolism . A total of 403 of these patients were randomized to receive once-daily treatment with aspirin 100 mg (n = 205) or placebo (n = 197) for 2 years, with the option of extending the study treatment. The primary efficacy outcome was recurrence of venous thromboembolism during a median study period of 24.6 months; the primary safety outcome was major bleeding. A secondary outcome was “on treatment” recurrence risk, which was examined during anticoagulant treatment and within 2 days after its withdrawal.
Venous thromboembolism recurred significantly less frequently in 28 of the 205 patients who received aspirin compared with 43 of 197 of those who took placebo (6.6% vs 11.2% per year); the hazard ratio was 0.58, with a 95% confidence interval (CI) of 0.36 to 0.93 (P = 0.02). The on-treatment risk analysis showed that 23 patients in the aspirin group and 39 in the placebo group had a recurrence (5.9% vs 11.0% per year; hazard ratio, 0.55; 95% CI, 0.33–0.92; P = 0.02). There were 2 episodes of nonfatal major bleeding, one in each group. Adverse events were similar in the 2 groups.
These findings show that aspirin therapy given after discontinuation of anticoagulant therapy in patients with unprovoked venous thromboembolism is effective in preventing recurrence, with no apparent increase in the risk of major bleeding.
From the Division of Internal and Cardiovascular Medicine and Stroke Unit, Department of Internal Medicine, University of Perugia, Perugia (C.B., G.A.); Galliera Hospital, Genoa (A.S.); Faenza Hospital, Faenza (E.B.); Arcispedale Santa Maria Nuova, Reggio Emilia (M.S.); Valduce Hospital, Como (M.B.); Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Casa Granda, Ospedale Maggiore Policlinico, Milan (M.M.); University of Insubria, Varese (W.A.); Baggiovara Hospital, Modena (M.R.V.); Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia (E.G.); and the Department of Cardiothoracic and Vascular Sciences, University of Padua, Padua (P.P.), Italy; and Medical University of Vienna, Vienna, Austria (S.E.).