After patients with unprovoked venous thromboembolism (VTE) complete a 6- to 18-month course of oral anticoagulation therapy, consider a switch to aspirin.1
STRENGTH OF RECOMMENDATION
A: Based on one well-designed, randomized controlled trial (RCT).
Becattini C, Agnelli G, Schenone A, et al. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med. 2012;366:1959-1967.
A 62-year-old patient comes to your office for follow-up of a primary unprovoked venous thromboembolus. He has been on an oral anticoagulant for 12 months. Should he continue anticoagulation therapy despite the increased risk for major bleeding?
Patients who survive VTE—defined as either deep venous thrombosis or pulmonary embolism—are put on anticoagulant therapy to prevent a recurrence, typically for 6 to 18 months. But about 20% of patients with unprovoked VTE have a recurrence within 2 years of anticoagulation withdrawal.2 Extending anticoagulation prevents recurrences but increases the risk of bleeding.3
Is aspirin a viable alternative?
Until recently, the efficacy of aspirin for the prevention of recurrent VTE was unknown. Becattini et al investigated it in the multicenter RCT detailed in this PURL.
STUDY SUMMARY: Aspirin can prevent recurrence with minimal risk
To determine whether aspirin was a viable alternative to oral anticoagulation, the researchers compared aspirin with placebo in patients with primary unprovoked VTE who had completed a course of oral anticoagulation treatment. To be considered for the study, patients had to be >18 years and have had their first-ever objectively confirmed, symptomatic unprovoked proximal deep vein thrombosis, pulmonary embolism, or both. They also had to have completed 6 to 18 months of anticoagulant therapy, with a target international normalized ratio (INR) of 2.0 to 3.0. Exclusion criteria included a history of cancer, clinically significant thrombophilia, atrial fibrillation, and a bleeding event that occurred during the course of anticoagulation therapy.
Becattini et al identified 403 eligible patients. Two weeks after stopping anticoagulation, patients were randomly assigned to receive either aspirin 100 mg once daily (n=205) or placebo (n=198) for 2 years. (One patient in the placebo group never received treatment.) At baseline, there were no significant differences in patient characteristics. All were evaluated every 3 months in the first year and every 6 months in the second year.
The primary efficacy outcome was objectively confirmed recurrent VTE. The primary safety outcome was major bleeding, defined as bleeding that occurred in a critical location (eg, intracranial bleeding), was associated with a decrease of hemoglobin of at least 2 g/dL, required a transfusion of 2 units of whole blood or red blood cells, or was fatal. Overt bleeding, which required medical intervention but did not meet the criteria for major bleeding, was a secondary safety outcome.
Twenty-eight of the 205 patients in the aspirin group experienced a recurrence, compared with 43 of the 197 patients on placebo (6.6% vs. 11.2% per year; hazard ratio [HR]=0.58; 95% confidence interval [CI], 0.36-0.93; P=.02). Adverse events were reported by 7 patients in the aspirin therapy group and 6 in the placebo group. One patient in each group experienced major bleeding, and 3 in each group experienced clinically relevant but nonmajor bleeding. Withdrawal rates were similar (10 in the treatment group vs 9 controls), as were the number of patients who developed new indications for aspirin or anticoagulation therapy or were lost to follow-up.