SAN DIEGO – Aspirin reduced the risk of recurrent symptomatic venous thromboembolism by about 40% when given over a 2-year period following 6-12 months of warfarin therapy, with no apparent increase in major bleeding.
The findings, presented during a press briefing at the annual meeting of the American Society of Hematology, suggest that aspirin is a valid alternative to oral anticoagulants in the extended treatment of venous thromboembolism (VTE).
"This has great implications for clinical practice because many patients on anticoagulant treatment after a first-ever VTE are stopped after the initial 6 months of therapy and then they receive nothing for secondary prevention," lead author Dr. Cecilia Becattini, an internist in the stroke unit at the University of Perugia (Italy), said in an interview. "Maybe aspirin is a great opportunity [for VTE prevention] instead of nothing, because warfarin has the complication of major bleeding."
For the multicenter study known as WARFASA, 402 patients with a first-ever unprovoked VTE who had completed 6-12 months of oral anticoagulant treatment were randomized to receive aspirin 100 mg daily (aspirin group) or placebo for at least 2 years (placebo group).
The primary efficacy outcome was objectively confirmed recurrent symptomatic VTE and VTE-related death. Clinically relevant (major and nonmajor) bleeding were the main safety outcomes. Bleeding was considered major if it was fatal, occurred in a critical organ, or was associated with a decrease in hemoglobin of greater than 2.0 g/dL or led to a transfusion of two units or greater of whole blood or red cells.
The mean age of patients was 64 years and 56% were male. Of the 402 patients, 205 were randomized to the aspirin group while 197 were randomized to the placebo group. During the study period, which was a mean 25 months, Dr. Becattini reported that a VTE recurrence occurred in 28 patients in the aspirin group (6.6% per patient-year) and in 43 patients in the placebo group (11.0% per patient-year). This translated into a hazard ratio of 0.58.
During the on-treatment study period, which was a mean of 22 months, a VTE recurrence occurred in 23 patients in the aspirin group (5.9% per patient-year) and in 39 patients in the placebo group (11% per patient-year). This translated into a hazard ratio of 0.55.
There was one case of major bleeding in each group and three cases of clinically relevant nonmajor bleeding in each group. There were six deaths in the aspirin group (1.4% per patient-year) and five deaths in the placebo group (1.3% per patient-year), a difference that was not statistically significant (HR 1.04).
In an interview, Dr. Charles S. Abrams, professor of medicine at the University of Pennsylvania, Philadelphia, called the study findings "intriguing" and said that a larger trial will be needed to confirm the findings. "I’m not sure what the reason for the difference [between the placebo and aspiring groups] is," said Dr. Abrams.
"One possibility is that it’s a relatively small trial. If you look at the incidence of recurrent clots in most circumstances, it’s usually about 8% per year when you stop that anticoagulant." In the WARFASA trial, he continued, the incidence of recurrent clots in the placebo and aspirin groups "flanked what you would normally expect. It makes you worry that’s some sort of a fluke."
For her part, Dr. Becattini acknowledged that a larger confirmatory trial is needed before the use of aspirin for extended treatment of VTE can be recommended. She said that she discusses the option with patients who are candidates for aspirin therapy. With aspirin, she said, "we can have an alternative to nothing. It is not just an alternative, but it is a safe alternative."
The study was supported by a grant-in-aid from Bayer Pharma to the University of Perugia. Dr. Becattini and her coauthors said they had no relevant conflicts of interest to declare.