Apixaban Not Superior to Enoxaparin for Clot Prevention in Medically Ill Patients

Orlando—The ADOPT (Apixaban Dosing to Optimize Protection from Thrombosis) trial found that treatment with 30 days of oral apixaban is no more effective than 1 to 2 weeks of injected enoxaparin for preventing venous thromboembolism (VTE) in acutely ill patients. Samuel Z. Goldhaber, MD, lead researcher, presented findings from ADOPT at the AHA meeting. The results were also reported in the New England Journal of Medicine [2011;365(23):2167-2177]. Because the efficacy and safety of prolonging prophylaxis for VTE in medically ill patients beyond hospital discharge remain uncertain, researchers hypothesized that extended prophylaxis with apixaban would be safe and more effective than short-term prophylaxis with enoxaparin. ADOPT was an international, multicenter, randomized, double-blind, controlled study conducted at 302 centers in 35 countries. Patients were randomly assigned in a 1:1 ratio to receive apixaban (n=3255) 2.5 mg twice daily for 30 days or subcutaneous enoxaparin (n=3273) at 40 mg once daily for 6 to 14 days followed by placebo. Patients were men and women >40 years of age hospitalized with congestive heart failure or acute respiratory failure. The primary end point was the 30-day composite of death related to VTE, fatal or nonfatal pulmonary embolism (PE), symptomatic deep-vein thrombosis (DVT), or asymptomatic proximal-leg DVT as detected with the use of systematic bilateral compression ultrasonography. Among the 4695 patients who could be evaluated for the primary outcome at day 30 (n=2211 in the apixaban group and n=2284 in the enoxaparin group), 2.7% of those given apixaban (n=60) had a VTE event (death, DVT, or PE), compared with 3.1% among patients given enoxaparin (n=70) for 6 to 14 days during hospitalization. This difference was not statistically significant. The researchers measured bleeding rates in the entire study population (n=6528) to assess treatment safety. Rates of total bleeding events were not significantly different between the 2 groups: 7.73% for apixaban and 6.81% for enoxaparin (relative risk [RR], 1.13; 95% confidence interval [CI], 0.95-1.34; P=.18) Rates of major bleeding—which led to death, stroke, or other serious events—were statistically higher with apixaban, compared with enoxaparin (0.47% vs 0.19%; RR, 2.58; 95% CI, 1.02-7.24; P=.04, respectively). Furthermore, the postparenteral VTE death rate was 0.92% among apixaban patients and 1.55% among enoxaparin patients. Postparenteral symptomatic death rate was 0.25% among apixaban patients and 0.56% among enoxaparin patients. Dr. Goldhaber noted that a major study limitation was that one third of the 6528 patients could not be evaluated for the primary efficacy end point because they lacked a follow-up systematic bilateral compression ultrasound examination of the leg. Therefore, this study was underpowered, and the 13% RR reduction did not achieve statistical significance. “It’s clear that the risk of VTE increases beyond the time of hospital discharge,” he said. “The uncertain fate of the discharged patient susceptible to dangerous clotting remains one of the last frontiers where we struggle to find effective and safe VTE prevention.”