Apixaban After the Initial Management of Pulmonary Embolism and Deep Vein Thrombosis With First-Line Therapy–Extended Treatment - AMPLIFY-EXT
Description:
The goal of the trial was to evaluate treatment with apixaban, a factor Xa inhibitor, compared with placebo among patients with venous thromboembolism who had completed 6-12 months of anticoagulation therapy.
Hypothesis:
Apixaban will prevent recurrent venous thromboembolism or death.
Study Design
- Placebo Controlled
- Randomized
- Parallel
- Blinded
- Stratified
Patient Populations:
- Patients at least 18 years of age with prior venous thromboembolism (deep vein thrombosis or pulmonary embolism) who had completed 6-12 months of anticoagulation therapy
Number of enrollees: 2,482
Duration of follow-up: 1 year
Mean patient age: 57 years
Percentage female: 42%
Exclusions:
- Contraindication to anticoagulation or antiplatelet therapy
- Hemoglobin <9 g/dl
- Platelet count <100,000 per mm3
- Serum creatinine >2.5 mg/dl (or creatinine clearance <25 ml/min)
- AST or ALT >2 times the upper limit of normal
- Total bilirubin >1.5 times the upper limit of normal
Primary Endpoints:
- Symptomatic recurrent venous thromboembolism or death
- Major bleeding
Secondary Endpoints:
- Clinically relevant nonmajor bleeding
- Major or clinically relevant nonmajor bleeding
Drug/Procedures Used:
Patients with venous thromboembolism who had completed 6-12 months of anticoagulation therapy were randomized to apixaban 2.5 mg twice daily (n = 840), apixaban 5 mg twice daily (n = 813), versus placebo twice daily (n = 829). Study drugs were administered for 12 months.
Principal Findings:
Overall 2,482 patients were randomized. The mean age was 57 years, 42% were women, mean weight was 86 kg, and initial diagnosis was deep vein thrombosis in 65% and pulmonary embolism in 35%.
The primary efficacy outcome, symptomatic recurrent venous thromboembolism or all-cause mortality, occurred in 3.8% of the apixaban 2.5 mg twice daily group, 4.2% of the apixaban 5 mg twice daily group, versus 11.6% of the placebo group (p < 0.001 for both comparisons).
All-cause mortality occurred in 0.8% of the apixaban 2.5 mg twice daily group, 0.5% of the apixaban 5 mg twice daily group, versus 1.7% of the placebo group.
The primary safety outcome, major bleeding, occurred in 0.2% of the apixaban 2.5 mg twice daily group, 0.1% of the apixaban 5 mg twice daily group, versus 0.5% of the placebo group (p = not significant [NS] for both comparisons).
Clinically relevant nonmajor bleeding occurred in 3.0% of the apixaban 2.5 mg twice daily group, 4.2% of the apixaban 5 mg twice daily group, versus 2.3% of the placebo group (p = NS for apixaban 2.5 mg vs. placebo; p < 0.05 for apixaban 5 mg vs. placebo).
Major or clinically relevant nonmajor bleeding occurred in 3.2% of the apixaban 2.5 mg twice daily group, 4.3% of the apixaban 5 mg twice daily group, versus 2.7% of the placebo group (p = NS for both comparisons).
Interpretation:
Among patients with venous thromboembolism who had completed 6-12 months of anticoagulation therapy, extended therapy with apixaban (2.5 mg or 5 mg twice daily) reduced symptomatic recurrent venous thromboembolism or death. Clinical benefit was accomplished without an increase in major bleeding; however, clinically relevant nonmajor bleeding was increased with apixaban 5 mg compared with placebo. Future research will need to examine an even longer duration of treatment.
References:
Agnelli G, Buller HR, Cohen A, et al., on behalf of the AMPLIFY-EXT Investigators. Apixaban for Extended Treatment of Venous Thromboembolism. N Engl J Med 2012;Dec 8:[Epub ahead of print].
Keywords: Pulmonary Embolism, Venous Thromboembolism, Venous Thrombosis, Pyrazoles, Factor Xa, Pyridones
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