Oral Apixaban for the Treatment of Acute Venous Thromboembolism

Study Questions:

What is the efficacy of apixaban compared with conventional anticoagulant therapy in patients with acute symptomatic venous thromboembolism?

Methods:

In AMPLIFY, a randomized, double-blind study, the investigators compared apixaban (at a dose of 10 mg twice daily for 7 days, followed by 5 mg twice daily for 6 months) with conventional therapy (subcutaneous enoxaparin, followed by warfarin) in 5,395 patients with acute venous thromboembolism. The primary efficacy outcome was recurrent symptomatic venous thromboembolism or death related to venous thromboembolism. The principal safety outcomes were major bleeding alone and major bleeding plus clinically relevant nonmajor bleeding.

Results:

The primary efficacy outcome occurred in 59 of 2,609 patients (2.3%) in the apixaban group, as compared with 71 of 2,635 (2.7%) in the conventional-therapy group (relative risk, 0.84; 95% confidence interval [CI], 0.60-1.18; difference in risk [apixaban minus conventional therapy], −0.4 percentage points; 95% CI, −1.3 to 0.4). Apixaban was noninferior to conventional therapy (p < 0.001) for predefined upper limits of the 95% CIs for both relative risk (<1.80) and difference in risk (<3.5 percentage points). Major bleeding occurred in 0.6% of patients who received apixaban and in 1.8% of those who received conventional therapy (relative risk, 0.31; 95% CI, 0.17-0.55; p < 0.001 for superiority). The composite outcome of major bleeding and clinically relevant nonmajor bleeding occurred in 4.3% of the patients in the apixaban group, as compared with 9.7% of those in the conventional-therapy group (relative risk, 0.44; 95% CI, 0.36-0.55; p < 0.001). Rates of other adverse events were similar in the two groups.

Conclusions:

The authors concluded a that fixed-dose regimen of apixaban alone was noninferior to conventional therapy for the treatment of acute venous thromboembolism.

Perspective:

This study shows that a fixed-dose regimen of oral apixaban alone was as effective as conventional treatment consisting of enoxaparin followed by warfarin for the treatment of acute venous thromboembolism, and was associated with a clinically relevant reduction of 69% in major bleeding. These data add to the evidence that the new oral anticoagulants are simple alternatives to conventional therapy for patients with acute venous thromboembolism. It appears that apixaban may provide a simple, effective, and safe regimen for the initial and long-term treatment of venous thromboembolism.

Clinical Topics: Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine

Keywords: Venous Thromboembolism


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