ADOPT

Apixaban for the prevention of thrombosis-related events in patients with acute medical illness (2011)

Condition

Prevention of VTE in patients hospitalized for acute medical illness

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Objective

To evaluate the safety and efficacy of apixaban versus enoxaparin for prophylaxis of VTE in acutely ill medical patients during and following hospitalization

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Trial design

Randomized, double-blind phase III study
Active treatment: while hospitalized: apixaban 2.5 mg p.o. twice daily plus placebo (syringes, s.c.) once daily for 6–14 days; after hospital discharge: apixaban 2.5 mg p.o. twice daily up to 30 days (= duration of double-blind treatment)
Control treatment: enoxaparin 40 mg s.c. once daily for 6–14 days plus placebo (tablets, p.o.) twice daily; after hospital discharge: placebo (tablets, p.o.) twice daily up to 30 days (= duration of double-blind treatment)

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Endpoints

Primary efficacy endpoint: 30-day composite of VTE-related death and fatal or non-fatal PE, symptomatic DVT, or asymptomatic proximal-leg DVT
Secondary efficacy endpoints: Additional secondary efficacy outcomes included the composite of total VTE and VTE-related death occurring from the time of randomization to the time the blinded parenteral therapy was discontinued (the parenteral-treatment period), all cause death during the 30-day treatment period and during the entire 90-day study period
Safety endpoints: major bleeding, clinically relevant non-major bleeding and all bleeding reported by investigators

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Trial participants

6528 patients ≥40 years, hospitalized for congestive heart failure, acute respiratory failure, infection (without septic shock), acute rheumatic disorder, or inflammatory bowel disease, who had an expected hospital stay of at least 3 days and were severely restricted in their mobility. 4495 patients could be evaluated for the primary efficacy outcome at day 30, 2211 in the apixaban group and 2284 in the enoxaparin group

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Results

Efficacy outcome: The primary efficacy outcome, the composite of VTE and death related to VTE, evaluated at day 30, occurred in 2.71% of the patients randomly assigned to receive extended prophylaxis with apixaban (60 of the 2211 patients in the primary efficacy data set) and in 3.06% of those assigned to receive short-term prophylaxis with enoxaparin (70 of 2284 patients) (relative risk with apixaban 0.87; p=0.44). After the parenteral-treatment period (analysis on day 10), the primary efficacy outcome occurred in 1.73% of patients in the apixaban group (43 of 2485 patients) and in 1.61% in the enoxaparin group (40 of 2488 patients) (relative risk 1.06). The rate of symptomatic DVT was lower among patients with apixaban than among those who received enoxaparin (0.15% vs. 0.49%), but this difference did not reach significance. There was no significant difference in the rate of death between the apixaban and the enoxaparin treated group (4.1% in each group, 131 and 133 patients, respectively)
Safety outcome: By day 30, major bleeding was two and a half times more likely in the apixaban group, occurring in 0.47% of patients (15 of the 3184 patients who received at least one dose of apixaban), compared with 0.19% of those in the enoxaparin group (6 of the 3217 patients who received at least one dose of enoxaparin) (relative risk with apixaban 2.58; p=0.04). Major plus clinically relevant non-major bleeding occurred in 2.67% of the patients with apixaban and in 2.08% of those treated with enoxaparin (relative risk 1.28; p=0.12). The rates of total bleeding events in the apixaban and enoxaparin groups were 7.73% and 6.81%, respectively (p=0.18).

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Summary

Efficacy: Prolonging prophylaxis for venous thromboembolism in medically ill patients with a 30-day course of the oral anticoagulant apixaban was not superior to a shorter six- to 14-day course of subcutaneous enoxaparin
Safety: Apixaban was associated with significantly more major bleeding events than was enoxaparin

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Reference

Goldhaber SZ, Leizorovicz A, Kakkar AK, Haas SK, Merli G, Knabb RM, Weitz JI, for the ADOPT Trial Investigators. Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. N Engl J Med 2011;365:2167-2177

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Corresponding author

Samuel Z. Goldhaber, MD, Brigham and Women’s Hospital, Cardiovascular Division, 75 Francis St., Boston, MA 02115, e-mail: sgoldhaber@partners.org

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