Archief Roodbont

December 12, 2011 (San Diego, California) — The use of aspirin reduces the risk of recurrent venous thromboembolism (VTE) by more than half when compared with placebo, according to the results of a new study [1]. Investigators say the reduction in VTE risk, which was achieved without an increased risk of bleeding, makes aspirin an attractive treatment option for the extended prevention of recurrent VTE once oral anticoagulation has been stopped.

"Patients with a first episode of VTE usually receive initial therapy with heparin, which is given for five to seven days, and then they are switched over to oral anticoagulants," lead investigator Dr Cecilia Becattini (University of Perugia, Italy) told heartwire . "Oral anticoagulant therapy [with vitamin-K antagonists] is not very practical, as it requires laboratory monitoring and medical visits for adjustments. More important, there is the potential for harmful bleeding complications with warfarin, which can occur in about 3% of patients."

The past couple of years have seen the emergence of more anticoagulants for VTE, including the US Food and Drug Administration approval of rivaroxaban (Xarelto, Bayer/Johnson & Johnson) for prevention of deep venous thrombosis (DVT) in the setting of knee- or hip-replacement surgery. Apixaban (Eliquis, Bristol-Myers Squibb/Pfizer) has been approved in Europe for the prevention of VTE events in adult patients who have undergone elective hip- or knee-replacement surgery, while edoxaban (Lixiana, Daiichi Sankyo), another direct factor Xa inhibitor, is approved in Japan. Data from the RECOVER trial also showed that the new anticoagulant dabigatran (Pradaxa, Boehringer Ingelheim) was effective when used in the VTE setting, and it is currently approved for use in Europe.

"There are a lot of new agents out there that don't require laboratory monitoring, and some of these new oral anticoagulants have already been approved for use in patients with venous thromboembolism," said Becattini. "But again, they are anticoagulants, and while they are effective, the risk of bleeding complications is not zero."

In this study, known as WARFASA, which was presented at the American Society of Hematology 2011 Annual Meeting, the researchers tested whether the use of aspirin therapy was more effective than placebo in reducing the risk of recurrent VTE in patients treated with warfarin for six to 18 months following the first idiopathic VTE. After the initial treatment with warfarin, the drug was stopped, and 205 patients were randomized to 100 mg aspirin once daily and 197 patients to placebo.

During the two-year study period, recurrent symptomatic VTE occurred in 28 patients in the aspirin arm and 43 patients in the placebo group (6.6% per patient-year vs 11.2% per patient-year, respectively). In multivariate analysis, aspirin reduced the risk of recurrent VTE 42% (hazard ratio 0.58; 95% CI 0.36–0.93) compared with placebo. The risk of major bleeding and clinically relevant nonmajor bleeding was identical in the aspirin- and placebo-treated patients, with one major bleed and three clinically relevant bleeds reported in both groups. There was no significant difference in mortality.

Not as Efficacious, But Not as Risky

To heartwire , Becattini said that the bleeding risk with aspirin is 10-fold lower than that of other oral anticoagulants, and this study shows that putting a patient on aspirin extended therapy lowers the risk of recurrence without any significant increase in bleeding. It is a practical, low-cost option for clinicians and patients, even though it is not as efficacious for the reduction of recurrent VTE as other agents.

"You have to consider that in clinical trials, dabigatran and rivaroxaban showed an 80% to 90% reduction in the risk of venous thromboembolism, which is about double what we found with aspirin," she said. "These are the newer agents, but we don't yet know everything about their potential side effects. As well, there is the issue of cost."

After a three- or six-month treatment course with oral anticoagulants, Becattini said her center typically evaluates the risk for recurrent VTE by assessing conditions that were present at the time of the first event, such as trauma or surgery. Recurrent VTE can occur in as many as one in five patients in the two-year period following the withdrawal of oral anticoagulants.

"In cases that were associated with transient risk factors, we know the risk of a second venous thromboembolism is very low," she said. "So after three or six months, oral anticoagulants are usually discontinued. After the first episode, we'll stop the drugs and advise the patient about symptoms, telling them to come back to the hospital at the first sign something might be wrong.