Oral apixaban for the treatment of acute venous thromboembolism.

Abstract

BACKGROUND:

Apixaban, an oral factor Xa inhibitor administered in fixed doses, may simplify the treatment of venous thromboembolism.

METHODS:

In this randomized, double-blind study, we 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 5395 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 2609 patients (2.3%) in the apixaban group, as compared with 71 of 2635 (2.7%) in the conventional-therapy group (relative risk, 0.84; 95% confidence interval [CI], 0.60 to 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% confidence intervals 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 to 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 to 0.55; P<0.001). Rates of other adverse events were similar in the two groups.

CONCLUSIONS:

A fixed-dose regimen of apixaban alone was noninferior to conventional therapy for the treatment of acute venous thromboembolism and was associated with significantly less bleeding (Funded by Pfizer and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00643201).

• Authors: Giancarlo Agnelli, Harry R Buller, Alexander Cohen, Madelyn Curto, Alexander S Gallus, Margot Johnson, Urszula Masiukiewicz, Raphael Pak, John Thompson, Gary E Raskob, Jeffrey I Weitz, AMPLIFY Investigators
• Journal: The New England journal of medicine (N Engl J Med) Vol. 369 Issue 9 Pg. 799-808 (Aug 29 2013) ISSN: 1533-4406 [Electronic] United States
• PMID: 23808982 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anticoagulants
• Enoxaparin
• Factor Xa Inhibitors
• Pyrazoles
• Pyridones
• apixaban
• Warfarin

Topics

• Acute Disease
• Administration, Oral
• Adult
• Aged
• Anticoagulants (administration & dosage, adverse effects, therapeutic use)
• Double-Blind Method
• Enoxaparin (adverse effects, therapeutic use)
• Factor Xa Inhibitors
• Female
• Follow-Up Studies
• Hemorrhage (chemically induced, mortality)
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Pyrazoles (administration & dosage, adverse effects)
• Pyridones (administration & dosage, adverse effects)
• Treatment Outcome
• Venous Thromboembolism (drug therapy)
• Warfarin (adverse effects, therapeutic use)