Following myocardial infarction (MI) and stroke, venous thromboembolism (VTE) is the third most common cause of vascular death in the general population.1 The American College of Chest Physicians (ACCP) recommend the use of a parenteral anticoagulant, such as a low-molecular-weight heparin (LMWH), for at least five days or until the international normalized ratio (INR) is ≥2.0 for more than 24 hours.2 Concurrent therapy with a vitamin K antagonist (VKA) should be initiated and continued for at least three months.2 While this treatment is effective, it is challenging and alternatives may exist. Apixaban (Eliquis®) is an oral factor Xa inhibitor already approved to treat stroke and systemic embolism in atrial fibrillation, and may simplify VTE treatment with regards to laboratory monitoring and drug interactions.3 The Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-Line Therapy (AMPLIFY) trial was conducted to compare apixaban with conventional therapy in patients with acute VTE.3
The AMPLIFY trial was a randomized, double-blind, double-dummy, non-inferiority trial comparing the safety and efficacy of apixaban treatment to conventional therapy of enoxaparin plus warfarin.3 Patients included were 18 years and older, and had a diagnosis of symptomatic proximal deep venous thrombosis (DVT), pulmonary embolism (PE), or both. Exclusion criteria consisted of patients with active bleeding, at high risk for bleeding, unable to tolerate medications in either treatment arm, or if the patient was already receiving treatment for a certain period of time. The primary efficacy outcome was a composite of recurrent symptomatic VTE or death related to VTE. Major bleeding was deemed the primary safety outcome, with a secondary safety outcome of major bleeding and clinically relevant non-major bleeding. Major bleeding was defined as a decrease in hemoglobin level of 2 g/dL or more, requiring a transfusion of 2 or more units of blood, occurring into a critical site, or contributing to death. Secondary endpoints included a composite of the primary endpoint plus death, and a composite of the primary endpoint plus death and major bleeding.3
The study randomized 5395 patients to be treated with either 10 mg of apixaban twice daily for the first 7 days followed by 5 mg twice daily for 6 months, or enoxaparin 1 mg/kg every 12 hours for at least 5 days and concurrent warfarin with an INR goal of 2.0 to 3.0 continued for 6 months.3 Each group also received the placebo treatment of the regimen they were not receiving. Baseline demographic and clinical characteristics were similar between the two groups. Median duration of enoxaparin treatment was 6.5 days and patients in the conventional therapy arm stayed within therapeutic INR range 61% of the time. Recurrent symptomatic VTE occurred in 59 of 2609 patients (2.3%) in the apixaban group compared with 71 of 2635 patients (2.7%) in the conventional therapy group (RR 0.84, 95% CI, 0.60 to 1.18, P<0.001 for non-inferiority). Major bleeding occurred in 15 of 2676 patients (0.6%) in the apixaban group and in 49 of 2689 patients (1.8%) in the conventional therapy group (RR 0.31, 95% CI, 0.17 to 0.55, P<0.001 for superiority). Apixaban proved to be superior to conventional therapy for the secondary efficacy outcome as well, with 73 of 2609 patients (2.8%) in the apixaban group having recurrent symptomatic VTE, VTE-related death, or major bleeding versus 118 of 2635 (4.5%) in the conventional therapy group (RR 0.62, 95% CI, 0.47 to 0.88, P<0.001). No other differences were observed for all other specified endpoints. 3
This study demonstrated that fixed-dose oral apixaban is as ...