"Extended Anticoagulation with Apixaban for Venous Thromboembolism".The New England Journal of Medicine. 2013. 368:699-708.
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Contents 1Clinical Question 2Bottom Line 3Major Points 4Guidelines 5Design 6Population 6.1Inclusion Criteria 6.2Exclusion Criteria 6.3Baseline Characteristics 7Interventions 8Outcomes 8.1Primary Outcomes 8.2Secondary Outcome 8.3Additional Analyses 8.4Adverse Events 8.5Subgroup Analysis 9Criticisms 10Funding 11Further Reading
For patients with venous thromboembolism who have completed 6 to 12 months of anticoagulation therapy, is extended anticoagulation with apixaban effective in preventing recurrence without increasing the risk of major bleeding?
Extended anticoagulation with apixaban at doses of 2.5 mg or 5 mg twice daily reduced the risk of recurrent venous thromboembolism without increasing the rate of major bleeding.
Venous thromboembolism, comprising deep-vein thrombosis and pulmonary embolism, is a leading cause of vascular disease-related mortality. Treatment beyond 6 to 12 months presents a challenge due to the inconvenience and bleeding risk associated with warfarin, the standard anticoagulant. AMPLIFY-EXT assessed apixaban, an oral factor Xa inhibitor, for extended thromboprophylaxis post initial anticoagulation.
As of the last knowledge update, no guidelines reflecting the results of this trial could be found.
- Multicenter, double-blind, randomized, placebo-controlled trial - N=2,486 - Apixaban 2.5mg (n=840) - Apixaban 5mg (n=813) - Placebo (n=829) - Setting: 328 centers in 28 countries - Enrollment: 2008-2011 - Follow-Up: 12 months - Analysis: Intention-to-treat - Primary Outcome: Composite of symptomatic recurrent venous thromboembolism or death from any cause
Inclusion Criteria - Age ≥18 years - Symptomatic deep-vein thrombosis or pulmonary embolism - 6-12 months of anticoagulation therapy completed - Clinical equipoise regarding continuation or cessation of anticoagulation Exclusion Criteria - Contraindication to continued anticoagulant therapy or need for ongoing treatment with other anticoagulants or antiplatelet agents - Blood dyscrasias and other exclusions outlined in the study protocol Baseline Characteristics - Demographic and clinical characteristics well balanced between groups
- Randomized in a 1:1:1 ratio to receive 2.5 mg or 5 mg of apixaban or placebo, all given twice daily for 12 months
Primary Outcomes - Composite of symptomatic recurrent venous thromboembolism or death from any cause was significantly lower with apixaban 2.5 mg (3.8%) and 5 mg (4.2%) compared to placebo (11.6%) Secondary Outcome - Composite of symptomatic recurrent venous thromboembolism or venous thromboembolism-related death; apixaban was superior to placebo - Rates of major bleeding were similar across apixaban and placebo groups Additional Analyses - Assessment of arterial thrombotic events alongside confirmatory results for efficacy and safety Adverse Events - Similar rates of adverse events across all groups Subgroup Analysis - Results were consistent among various defined subgroups
- More data needed to determine benefit-to-risk profile in specific populations such as older patients, or those with low body weight or renal impairment - Limited data on extended treatment beyond 18 to 24 months
Funded by Bristol-Myers Squibb and Pfizer
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