Venous thromboembolism (VTE) including pulmonary embolism (PE) and deep vein thrombosis (DVT), is the third most common cardiovascular disease after MI and stroke. The condition causes between 100,000 and 180,000 deaths per year in the U.S. alone.1 Therefore, VTE is a major US health problem, and remains a problem in hospitalized patients. It is also evident that the risk of VTE increases beyond the time of hospital discharge; extending VTE prophylaxis has been the routine practice for patients undergoing total hip replacement or other high-risk orthopedic surgery.2,3
Extending prophylaxis however, in medically ill patients beyond hospital discharge, remains uncertain. The Extended Prophylaxis for Venous Thromboembolism in Acutely Ill Medical Patients with Prolonged Immobilization (EXCLAIM) and the Venous Thromboembolic Event (VTE) Prophylaxis in Medically Ill Patients (MAGELLAN) trials reported the event rates of VTE at 30 days to be 5% and 6%, respectively. The EXCLAIM trial found lower rates of VTE with extended prophylaxis with subcutaneous enoxaparin for an average period of 28 days compared with placebo. This benefit however was offset by a significant increase in major bleeding in the enoxaparin group.4 Similarly, the MAGELLAN trial examined extended prophylaxis with rivaroxaban 10 mg once daily compared with short-term prophylaxis with enoxaparin (10 days, 40 mg per day) followed by placebo. Again, lower rates of VTE in the rivaroxaban group were offset by more major bleeding events.5
The recently published Apixaban Dosing to Optimize Protection from Thrombosis (ADOPT) trial is a double-blind, double-dummy, placebo-controlled trial conducted at 302 centers in 35 countries. The study included acutely ill patients with congestive heart failure, respiratory failure or other medical disorders and at least one additional risk factor for VTE. Patients, who were hospitalized with an expected stay of at least three days, were randomly selected to receive apixaban (2.5 mg orally twice daily for 30 days) or enoxaparin (40 mg subcutaneously once daily for 6 to 14 days). The primary efficacy outcome was the 30-day composite of death related to VTE, PE, symptomatic deep vein thrombosis (DVT) or asymptomatic proximal-leg DVT, as detected with the use of systematic bilateral compression ultrasonography at 30 days. The primary safety outcome was bleeding.6
A total of 4495 were evaluated for the primary efficacy outcome, 2211 in the apixaban group and 2284 in the enoxaparin group. Only 2.71% in the apixaban group and 3.06% in the enoxaparin group met the criteria for the primary efficacy outcome, a 13% relative risk reduction. The extended course of thromboprophylaxis with apixaban was not found to be superior to enoxaparin and led to more bleeding. Major bleeding occurred in 0.47% of patients in the apixaban group and in 0.19% of patients in the enoxaparin group. The resulting 2.58-fold increased relative risk of major bleeding in the apixaban group was significant. The investigators noted that as soon as enoxaparin prophylaxis stopped, the rate of symptomatic VTE or VTE-related death occurred in 0.56% in the enoxaparin arm compared with 0.25% ...