"Apixaban versus Conventional Therapy in Venous Thromboembolism".The New England Journal of Medicine. 2013. 369:799-808.PubMed•Full text•PDF

Contents

1 Clinical Question
2 Bottom Line
3 Major Points
4 Guidelines
5 Design
6 Population
6.1 Inclusion Criteria
6.2 Exclusion Criteria
6.3 Baseline Characteristics
7 Interventions
8 Outcomes
8.1 Primary Outcome
8.2 Secondary Outcomes
9 Criticisms
10 Funding
11 Further Reading

Clinical Question

Does a fixed-dose regimen of apixaban alone compare to conventional therapy with enoxaparin followed by warfarin in patients with acute venous thromboembolism?

Bottom Line

For the treatment of acute venous thromboembolism, apixaban was noninferior to conventional therapy and was associated with significantly less bleeding.

Major Points

Guidelines

Updated guidelines now need to consider the evidence from this trial when prescribing therapy for acute venous thromboembolism.

Design

- Multicenter, double-blind, randomized, controlled trial
- N=5395 patients with acute venous thromboembolism
- Apixaban group (n=2609)
- Conventional therapy group (n=2635)
- Setting: 358 centers in 28 countries
- Enrollment: August 2008 to August 2012
- Mean follow-up: 6 months
- Analysis: Intention-to-treat
- Primary outcome: Recurrence of symptomatic venous thromboembolism or death related to venous thromboembolism

Population

Inclusion Criteria

- Age ≥18 years
- Symptomatic proximal deep-vein thrombosis or pulmonary embolism (with or without deep-vein thrombosis)

Exclusion Criteria

- Active bleeding or high risk of bleeding
- Cancer with planned long-term low-molecular-weight heparin therapy
- Provoked venous thromboembolism without a persistent risk factor for recurrence
- Life expectancy less than 6 months
- Other indications for chronic anticoagulation or dual antiplatelet therapy
- Certain laboratory abnormalities

Baseline Characteristics

- Demographic and clinical characteristics were similar in both groups

Interventions

- Apixaban group: 10 mg twice daily for 7 days, followed by 5 mg twice daily for 6 months
- Conventional therapy group: Enoxaparin followed by warfarin for 6 months with adjustments to maintain INR between 2.0 and 3.0

Outcomes

Primary Outcome

- Recurrence of symptomatic venous thromboembolism or death related to venous thromboembolism occurred in 2.3% of the apixaban group versus 2.7% of the conventional therapy group (P<0.001 for noninferiority)

Secondary Outcomes

- Major bleeding occurred in 0.6% of the apixaban group versus 1.8% of the conventional therapy group (P<0.001 for superiority)
- The composite outcome of major bleeding and clinically relevant nonmajor bleeding occurred in 4.3% of the apixaban group versus 9.7% of the conventional therapy group (P<0.001)

Criticisms

- Further information is needed pertaining to the efficacy and safety of apixaban in patients with cancer, low body weight, or a creatinine clearance of less than 50 ml per minute.

Funding

- The study was funded by Pfizer and Bristol-Myers Squibb.

Further Reading

- The full text of the study is available at NEJM.org with supplementary materials detailing the protocol and full trial appendix.