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Phase 3 Trials Compare Apixaban and Enoxaparin in Treating VTE

Authors

Tim Casey

Orlando—A pooled analysis of two phase 3 randomized, double-dummy studies found that apixaban was more effective than enoxaparin in preventing venous thromboembolism (VTE) after patients underwent hip or knee replacement surgery. The authors also concluded that apixaban did not increase bleeding and had advantages such as oral administration and later initiation after surgery. Gary E. Raskob, PhD, the study’s lead author, discussed the results during a press briefing and an oral abstract session at the ASH meeting. The ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation) trials evaluated the efficacy of twice daily doses of 2.5 mg apixaban, a novel oral antithrombotic drug and a direct, reversible factor Xa inhibitor. ADVANCE-1 evaluated apixaban versus 30 mg of enoxaparin twice daily after total knee replacement surgery, ADVANCE-2 evaluated apixaban versus 40 mg of enoxaparin once daily after total knee replacement surgery, and ADVANCE-3 evaluated apixaban versus 40 mg of enoxaparin once daily after total hip replacement surgery. The authors pooled the data from ADVANCE-2 and ADVANCE-3 to provide more precise event rate estimates of major VTE and bleeding as well as safety outcomes of myocardial infarction (MI) and stroke. They did not include results from ADVANCE-1 because the dosage differed in that trial, whereas ADVANCE-2 and ADVANCE-3 had the same dosage. ADVANCE-2 included 1528 patients who took apixaban and 1529 patients who took enoxaparin. ADVANCE-3 included 2708 patients in the apixaban group and 2699 patients in the enoxaparin group. The pooled analysis focused on serious blood clots in the large veins in the thighs or lungs. The trials administered apixaban 12 to 24 hours after surgery (mean, 19 hours), while enoxaparin was administered 9 to 15 hours before surgery (mean, 13 hours) and resumed after surgery (mean, 19 hours). The medications continued 10 to 14 days after surgery in ADVANCE-2 and 32 to 38 days after surgery in ADVANCE-3. At the end of the treatment period, both trials had a mandatory bilateral venography. Of the 8464 patients in ADVANCE-2 and ADVANCE-3, the researchers in the pooled analysis evaluated a total of 6788 patients (3394 from each trial). Major VTEs occurred in 23 patients in the apixaban group and 51 patients in the enoxaparin group; major bleeding occurred in 31 patients taking apixaban (including 26 at the surgical site) and 32 patients taking enoxaparin (including 27 at the surgical site). The apixaban group had 10 patients who suffered from MI (including 6 during treatment) and 3 patients who had a stroke (all during treatment). Among the enoxaparin patients, 5 had MIs (including 4 during treatment) and 5 had a stroke (including 4 in treatment).

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