Credit: Kevin MacKenzie
ATLANTA—Due to results of the AMPLIFY-EXTENSION study, researchers are recommending a new indication for apixaban: long-term use to prevent recurrent venous thromboembolism (VTE).
Study investigators compared 12 months of treatment with apixaban at 2 doses—2.5 mg and 5 mg—to placebo in patients who had previously received anticoagulant therapy for 6 to 12 months to treat a prior VTE.
The team found that both doses of apixaban effectively prevented VTE, VTE-related events, and death. And the incidence of bleeding events was low in all treatment arms.
“We believe that the study, given the results we achieved, should support the use of apixaban for the extended treatment of VTE,” said Giancarlo Agnelli, MD, of the University of Perugia in Italy.
Dr Agnelli presented these results in the late-breaking abstract session (LBA-1) of the 54th ASH Annual Meeting, which took place here December 8-11.
More detailed results of the study—which was funded by Bristol-Myers Squibb and Pfizer, joint developers of apixaban—have been published in NEJM.
Dr Agnelli noted that apixaban has proven effective as VTE prophylaxis when given at 2.5 mg after hip or knee replacement surgery. And the drug has been administered at 5 mg as stroke prevention in patients with atrial fibrillation.
So he and his colleagues wanted to determine if apixaban might be effective as long-term VTE prophylaxis in patients with a previous thrombotic event, as well as which dose might be optimal for these patients.
To find out, the researchers enrolled 2482 patients with a prior VTE who had completed 6 to 12 months of oral anticoagulant treatment without VTE recurrence or bleeding.
The team randomized 840 patients to receive apixaban at 2.5 mg BID, 813 patients to receive the drug at 5 mg BID, and 829 patients to receive placebo.
The patients were well-matched according age, gender, weight, initial diagnosis, and VTE clinical presentation. They received treatment for 12 months, after which they were followed for 30 days.
Efficacy data
The study’s primary efficacy endpoint was recurrent VTE or all-cause death. During the 12-month active study period, these events occurred in 32 patients (3.8%) in the 2.5-mg arm, 34 patients (4.2%) in the 5-mg arm, and 96 patients (11.6%) in the placebo arm. Both apixaban doses were significantly superior to placebo (P<0.001).
The researchers also calculated the incidence of recurrent VTE or VTE-related death. And these events occurred in 14 patients (1.7%) in the 2.5-mg arm, 14 patients (1.7%) in the 5-mg arm, and 73 patients (8.8%) in the placebo arm. Both apixaban doses were significantly superior to placebo (P<0.001).
A third composite endpoint consisted of recurrent VTE, VTE-related death, myocardial infarction, stroke, or cardiovascular-related death. This endpoint was met by 18 patients (2.1%) in the 2.5-mg arm, 19 patients (2.3%) in the 5-mg arm, and 83 patients (10.0%) in the placebo arm.
Overall, both doses of apixaban reduced the risk of fatal and non-fatal recurrent venous thromboembolism by 80%, Dr Agnelli said.
Events during follow-up
During the 30-day follow-up period, symptomatic, recurrent VTE occurred in 2 patients (0.2%) who had received placebo, 3 patients (0.4%) who had received apixaban at 2.5 mg, and 5 patients (0.6%) who had received apixaban at 5 mg.
The composite outcome of myocardial infarction, stroke, or death related to cardiovascular disease occurred in 2 patients: 1 who had received the lower dose of apixaban and 1 who received the higher dose.
Safety data
The study’s primary safety endpoint was major bleeding. In the 2.5-mg arm, 2 patients (0.2%) experienced major bleeding events, both of which were intraocular bleeds.
One patient (0.1%) in the 5-mg arm experienced a major gastrointestinal bleed. And 4 patients (0.5%) in the placebo arm experienced major bleeding events, including 1 intraocular bleed, 1 stroke, 1 urogenital bleed, and 1 gastrointestinal bleed.
A secondary endpoint was clinically relevant, non-major bleeding. This occurred in 25 patients (3.0%) in the 2.5-mg arm, 34 patients (4.2%) in the 5-mg arm, and 19 patients (2.3%) in the placebo arm.
Dr Agnelli and his colleagues also combined the major bleeding data and the clinically relevant, non-major bleeding data. So 27 patients (3.2%) in the 2.5-mg arm had a bleeding event of either kind, as did 35 patients (4.3%) in the 5-mg arm and 22 patients (2.7%) in the placebo arm.
Clinical interpretation
Finally, the researchers tried to put this data into a clinical context. They calculated the number of patients needed to treat 1 recurrent VTE in each of the apixaban arms. And they found that number was 14 patients per year with both doses of the drug.
The team also calculated the number of patients needed to inflict harm, in the form of 1 major or clinically relevant, non-major bleeding event. And they found that number was 200 patients per year in the 2.5-mg arm and 63 patients per year in the 5-mg arm.
In closing, Dr Agnelli said these results support the use of apixaban as long-term thromboprophylaxis in patients with a prior VTE.
“And, as a matter of speculation, we do believe that, given the similar efficacy and the possibility of less clinically relevant non-major bleeding, the dose of 2.5 mg of apixaban would be preferred by the clinician,” he added.
