James Douketis, MD
In patients having total hip replacement (THR), what are the efficacy and safety of thromboprophylaxis with apixaban compared with enoxaparin?
Randomized placebo-controlled trial (Apixaban Dosed Orally Versus Anticoagulation with Injectable Enoxaparin to Prevent Venous Thromboemblism 3 [ADVANCE-3] trial). ClinicalTrials.gov NCT00423319.
Blinded (patients, clinicians, outcome adjudicators, and safety committee).*
Mean 36 days.
160 centers in 21 countries.
5407 patients (mean age 61 y, 53% women) scheduled for elective THR or revision of a hip prosthesis. Exclusion criteria included active bleeding, contraindication to anticoagulant prophylaxis, and need for ongoing anticoagulant or antiplatelet treatment.
Apixaban, 2.5 mg orally twice daily for 32 to 38 days starting after surgery, and once daily subcutaneous placebo injections (n = 2708), or subcutaneous enoxaparin, 40 mg/d, beginning 12 hours before surgery and continued according to the investigator’s standard of care, plus placebo tablets twice daily (n = 2699).
Primary outcome was a composite of deep venous thrombosis, nonfatal pulmonary embolism, or death from any cause during treatment. The secondary outcome was a composite of proximal deep venous thrombosis, nonfatal pulmonary embolism, or death from venous thromboembolism during the treatment period. Safety outcomes included major bleeding.
71% for primary composite outcome (29% had no or suboptimal venograms), 81% for secondary composite outcome, and 99% for safety outcomes.
The main results are in the Table.
In patients having total hip replacement, apixaban reduced venous thromboembolism more than enoxaparin without increasing risk for major bleeding.
Thromboprophylaxis with apixaban vs enoxaparin in total hip replacement†
†Abbreviations defined in Glossary. RRR, RRI, NNT, and CI calculated from data in article.
‡Deep venous thrombosis (1.1% vs 3.6%), nonfatal pulmonary embolism (<0.1% vs 0.2%), and death (0.1% vs <0.1%).
§Proximal deep venous thrombosis (0.3% vs 0.9%), nonfatal pulmonary embolism (<0.1% vs 0.2%), and venous thromboembolism death (<0.1% vs 0%).
||Acute, clinically overt bleeding accompanied by ≥ 1 of decrease in hemoglobin level of ≥ 2 g/dL over a 24-h period; transfusion of ≥ 2 units of packed red blood cells; bleeding at a critical site; bleeding into the operated joint necessitating reoperation or intervention; intramuscular bleeding with the compartment syndrome; or fatal bleeding.
Douketis J. Apixaban reduced VTE and did not increase major bleeding compared with enoxaparin in hip replacement. Ann Intern Med. ;154:JC5–7. doi: 10.7326/0003-4819-154-10-201105170-02007
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Published: Ann Intern Med. 2011;154(10):JC5-7.
Prevention/Screening, Venous Thromboembolism.
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