"Extended Anticoagulation with Apixaban for Venous Thromboembolism".The New England Journal of Medicine. 2013. 368:699-708.PubMed•Full text•PDF

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

Clinical Question

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?

Bottom Line

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.

Major Points

Guidelines

As of the last knowledge update, no guidelines reflecting the results of this trial could be found.

Design

- 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

Population

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

Interventions

- 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

Outcomes

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

Criticisms

- 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

Funding

Funded by Bristol-Myers Squibb and Pfizer

Further Reading

The full text of the article and supplementary materials can be found at NEJM.org