Venous thromboembolism is a frequent problem in cancer patients, and approximately 20% of all patients who develop the disease have a recurrence. Extending treatment with two fixed doses of the investigational agent apixaban, a factor Xa inhibitor without laboratory monitoring, may provide a simple, effective, and safe strategy for long-term management of venous thromboembolism, according to a study presented at the 54th Annual Meeting of the American Society of Hematology in Atlanta.¹

Acceptable Safety

“Both doses of anticoagulant reduced the risk of recurrent venous thromboembolism by about 80%. The rates of major bleeding were low and comparable to those in the placebo group,” said lead author Giancarlo Agnelli, MD, Professor of Internal Medicine and Director of the Department of Internal and Cardiovascular Medicine and Stroke Unit at Perugia University Hospital in Perugia, Italy. “This regimen has the potential to eliminate many of the challenges we face when treating patients with warfarin, including drug and food interactions, and the need for ongoing monitoring, which can simplify ongoing management of this condition.”

Dr. Agnelli and coauthors calculated that the number of patients needed to treat to prevent 1 episode of recurrent or nonfatal venous thromboembolism is 14, which is low and acceptable, he said. On the other hand, the number of patients needed to treat to cause 1 episode of major or clinically relevant nonmajor bleeding is 200.

The randomized, double-blind, placebo-controlled AMPLIFY-EXT study compared two doses of apixaban—2.5 mg and 5 mg—given as secondary prophylaxis vs placebo in patients with deep-vein thrombosis/venous thromboembolism who had completed 6 to 12 months of anticoagulant therapy. Patients were treated with apixaban for 12 months. Safety data were evaluated 30 days after treatment initiation.

Key Results

The primary endpoint of symptomatic recurrent venous thromboembolism or all-cause death occurred in 3.8% of patients on the 2.5-mg dose and 4.2% on the 5 mg-dose vs 11.6% on placebo. Recurrent venous thromboembolism or thrombosis-related death was reported in 1.7% of patients on the 2.5-mg dose, 1.7% on the 5-mg dose, and 8.8% of the placebo group. Recurrent thrombosis, thrombosis-related death, myocardial infarction, stroke, or cardiovascular-related deaths were reported in 2.1% of the 2.5-mg group, 2.3% of the 5-mg group, and 10% of placebo patients.

“Both doses of apixaban reduced the risk of recurrent [venous thromboembolism and venous thromboembolism–related] death by 80%,” Dr. Agnelli stated. The rates of major bleeding associated with both doses of apixaban were similar to placebo: 0.2% with 2.5 mg, 0.1% with 5 mg, and 0.5% with placebo. These data will be part of the submission package to the FDA, but have not yet been submitted, he noted.

The optimal duration of treatment with apixaban is not yet established. In this study, 1 year of treatment achieved risk reduction in venous thromboembolism without increased risk of major bleeding.■

Disclosure: Dr. Agnelli reported no potential conflicts of interest.

Reference

1. Agnelli GC, Buller HR, Cohen A, et al: Two doses of apixaban for the extended treatment of venous thromboembolism. 2012 ASH Annual Meeting. Abstract LBA-1. Presented December 11, 2012.