Prophylaxis with Apixaban for Acutely Ill Patients

A double-blind study evaluating the safety and efficacy of extended prophylaxis with apixaban for venous thromboembolism in acutely ill patients found that the extended treatment was not superior to short-term prophylaxis with enoxaparin; however, it was associated with significantly more major bleeding events. These findings and others from the ADOPT (Apixaban Dosing to Optimize Protection from Thrombosis) trial were published online in the New England Journal of Medicine [10.1056/NEJMoa1110899]. Pharmacologic thromboprophylaxis has been shown to have benefits for surgical patients and acutely ill medical patients during hospital stays; however, the efficacy and safety of prolonging prophylaxis for venous thromboembolism in medically ill patients beyond the hospital stay is unclear. In this multicenter, placebo-controlled trial, researchers evaluated the safety and efficacy of using apixaban, an orally active direct inhibitor of activated factor X (factor Xa), to prevent thromboembolism in acutely ill patients during their hospital stay and during an extended period following discharge. Researchers randomized 6528 patients who were hospitalized with an expected stay of at least 3 days and had either moderately restricted or severely restricted mobility to receive either 2.5 mg of apixaban twice daily for 30 days or 40 mg of enoxaparin once daily for 6 to 14 days. Participants in the study were ≥40 years of age and were hospitalized for congestive heart failure or acute respiratory failure. Patients with infection without septic shock, acute rheumatic disorder, or inflammatory bowel disease were also eligible if they also possessed 1 of the following risk factors: previous documented venous thromboembolism or a history of venous thromboembolism that had been treated with anticoagulation for at least 6 weeks, were ≥75 years of age, cancer, a body mass index ≥30, received estrogenic hormone therapy, or had chronic heart failure or respiratory failure. Patients were enrolled in the study at 302 centers in 35 countries from June 2007 to February 2011. Researchers identified the primary efficacy outcome in the ADOPT trial as the 30-day composite of death related to venous thromboembolism, pulmonary embolism, symptomatic deep-vein thrombosis, or asymptomatic proximal-leg deep-vein thrombosis based on results from a systematic bilateral compression ultrasonography on day 30. The primary safety outcome of the trial was bleeding. Based on the results, researchers found that the extended treatment with apixaban was not superior to the shorter treatment with enoxaparin. They reported that of the 4495 patients who were evaluated for the primary efficacy outcome at the 30-day mark, 2.71% of patients in the extended prophylaxis with apixaban group and 3.06% of those in the enoxaparin group met the primary efficacy outcome (relative risk with apixaban, 0.87; 95% confidence interval [CI], 0.62-1.23; P=.44). However, researchers did find that there was significantly more major bleeding events among those in the apixaban group (0.47%) compared with those in the enoxaparin group (0.19%) (relative risk with apixaban, 2.58; 95% CI, 1.02-7.24; P=.04). The total bleeding rates were also higher in the apixaban group, but the difference was not statistically significant (7.73% vs 6.81% in the enoxaparin group; relative risk, 1.13; 95% CI, 0.95-1.34; P=.18). Researchers noted there were no significant differences between the groups when evaluating rates of death or adverse events. The study’s authors highlighted several strengths of the study including the large sample size, the double-blind design, and randomization. They also acknowledged some limitations, including the inclusion of asymptomatic proximal deep-vein thrombosis as part of the primary efficacy outcome and a follow-up ultrasound examination rate of only 64% of patients, which reduced the statistical power of the trial.