After patients with unprovoked venous thromboembolism (VTE) complete a 6- to 18-month course of oral anticoagulation therapy, consider a switch to aspirin.1
A: Based on one well-designed, randomized controlled trial (RCT).
A 62-year-old patient comes to your office for follow-up of a primary unprovoked VTE. 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 (DVT) or pulmonary embolism (PE)—are put on anticoagulant therapy to prevent a recurrence, typically for six to 18 months. But about 20% of patients with unprovoked VTE have a recurrence within two years of anticoagulation withdrawal.2 Extending anticoagulation prevents recurrences but increases the risk for bleeding.3
Is aspirin a viable alternative?
Until recently, the efficacy of aspirin for the prevention of recurrent VTE was unknown. Becattini et al1 investigated it in the multicenter RCT detailed in this PURL.
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 older than 18 and have had their first-ever objectively confirmed, symptomatic unprovoked proximal DVT PE, or both. They also had to have completed six 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/d (n = 205) or placebo (n = 198) for two years. (One patient in the placebo group never received treatment.)
At baseline, there were no significant differences in patient characteristics. All were evaluated every three months in the first year and every six 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 two 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).
Adverse events were reported by seven patients in the aspirin therapy group and six in the placebo group. One patient in each group experienced major bleeding, and three in each group experienced clinically relevant but nonmajor bleeding.
Withdrawal rates were similar (10 in the group receiving aspirin vs 9 in the group receiving placebo), as were the number of patients who developed new indications for aspirin or anticoagulation therapy or were lost to follow-up.
An analysis adjusted for age, sex, index event (DVT or PE) and duration of initial anticoagulation treatment confirmed that aspirin reduced the risk for recurrence (adjusted HR = 0.53). No association was found between recurrent VTE and duration of anticoagulation therapy (six months vs longer). Nor was there a difference in recurrence rates based on the index event.
Aspirin has a key role
in preventing recurrence
This study found that for patients with unprovoked VTE who completed a course of oral anticoagulation, aspirin was effective in preventing a recurrence, with no apparent increase in the risk for major bleeding. Protection in year 2 was nearly as great as in year 1.1
Patients were followed
for just two years
It is unclear whether continuing aspirin therapy beyond two years would continue to confer protection against a VTE recurrence without an increase in adverse effects.
CHALLENGE TO IMPLEMENTATION
Some patients can't tolerate chronic aspirin therapy
Although this study investigated aspirin in a dosage of 100 mg/d, this strength is not readily available in the United States.4 There is no evidence to suggest that the 81-mg strength that is available in this country would provide a diminished antiplatelet effect.
And, as is already customary, patients undergoing chronic aspirin therapy must be monitored for major bleeding, GI irritation, and renal compromise. A few patients will be ineligible for prophylaxis due to a history of intolerance to aspirin or NSAIDs.