Oral Apixaban for the Treatment of Acute Venous Thromboembolism
Abstract & Commentary
By Harold L. Karpman, MD, FACC, FACP
Clinical Professor of Medicine, UCLA School of Medicine
Dr. Karpman reports no financial relationships relevant to this field of study.
Synopsis: A fixed dose of oral apixaban alone was noninferior to conventional therapy for the treatment of acute venous thromboembolism and was associated with significantly less bleeding.
Source: Agnelli G, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013;369:799-808.
Venous thromboembolism occurs only one to two times per 1000 persons in the general population of the United States. However, it is the third most common cause of vascular death after myocardial infarction and stroke.1 Conventional therapy consists of a parenteral anticoagulant such as enoxaparin for at least 5 days and warfarin, which should also be started upon diagnosis and continued for at least 3 months.2 This classic therapeutic regimen is moderately inconvenient, especially in remote geographic regions, both because enoxaparin requires daily subcutaneous injections and because warfarin therapy requires coagulation monitoring and dose adjustment. The oral factor Xa inhibitor apixaban has a rapid onset of action and predictable pharmacokinetics that permits a fixed-dose regimen that significantly simplifies the treatment of venous thromboembolism by eliminating the need for both the initial parenteral anticoagulant therapy and subsequent laboratory monitoring of warfarin therapy.3,4
Although apixaban had been demonstrated to be effective for the prevention of recurrent venous thromboembolism with rates of major bleeding that are similar to those for placebo,5 Agnelli and his colleagues decided to compare apixaban with conventional anticoagulant therapy in patients with acute symptomatic venous thromboembolism.6 In this randomized, double-blind study, apixaban therapy (at a dose of 10 mg twice daily for 7 days, followed by 5 mg twice daily for 6 months) was compared with conventional therapy of subcutaneous enoxaparin followed by warfarin therapy in 5395 patients with acute venous thromboembolism. The primary efficacy outcomes were the avoidance of recurrent symptomatic venous thromboembolism or death related to venous thromboembolism. The principal safety outcomes were the occurrence of major bleeding alone or clinically relevant nonmajor bleeding. The results revealed that the primary efficacy outcome occurred in 2.3% of the apixaban group compared with 2.7% in the conventional therapy group. Therefore, apixaban proved to be not inferior to conventional therapy. Major bleeding occurred in 0.6% of patients receiving apixaban and in 1.8% of patients who received conventional therapy. Major bleeding and clinically relevant nonmajor bleeding occurred in 4.3% of the patients in the apixaban group and in 9.7% of the conventional therapy group.
For the treatment of acute venous thromboembolism, this well-conducted, multicenter study clearly demonstrated that a fixed-dose regimen of oral apixaban alone was as effective as conventional treatment and, equally important, it was associated with a clinically relevant reduction of 69% in major bleeding episodes.6 The reduction in major bleeding was paralleled by a decrease in clinically relevant nonmajor bleeding, which thereby provided further evidence for the safety of the apixaban regimen. These results added to the previously published evidence3,4 that simple therapy with one of the newer oral anticoagulants proved to be an excellent alternative to conventional therapy for patients with acute venous thromboembolic conditions. The efficacy of apixaban in patients with pulmonary embolism was similar to that in patients with deep venous thrombosis. The efficacy and safety of apixaban also proved to be consistent across a broad range of subgroups, including patients who were > 75 years or who were obese. On the basis of the results obtained in this current study as well as in other studies such as the Apixaban for the Extended Treatment of Deep Vein Thrombosis and Pulmonary Embolism trial,5 oral apixaban appears to be a simple, effective, and safe drug for the initial and long-term treatment of venous thromboembolism.
- Goldhaber SZ, et al. Pulmonary embolism and deep vein thrombosis. Lancet 2012;379:1835-1846.
- Kearon C, et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 Suppl):e419S-94S. Erratum, Chest 2012;142:1698-1704.
- The EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010;363:2499-2510.
- The EINSTEIN-PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism.
N Engl J Med 2012;366:1287-1297.
- Agnelli G, et al. Apixaban for extended treatment of venous thromboembolism. N Engl J Med 2013;368:699-708.
- Agnelli G, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013; 369:799-808.