title: Apixaban after hip or knee arthroplasty versus enoxaparin: efficacy and safety in key clinical subgroups.
abstract: BACKGROUND
  New oral anticoagulants for thromboprophylaxis after hip or knee arthroplasty have been given as fixed-dose regimens.
  
  
  OBJECTIVE
  To evaluate the consistency of the antithrombotic efficacy and bleeding risk of apixaban 2.5 mg twice daily compared with enoxaparin 40 mg once daily after knee or hip arthroplasty across the clinical characteristics of age, gender, body weight, body mass index (BMI) and creatinine clearance.
  
  
  METHODS
  The pooled results of the ADVANCE-2 (knee arthroplasty) and -3 (hip arthroplasty) randomized trials were used to evaluate if treatment had a statistically significantly different effect (P < 0.10) on major venous thromboembolism (VTE) and bleeding for the characteristics of age, gender, body weight, BMI and creatinine clearance. Both univariate analysis and multivariate logistic regression were used.
  
  
  RESULTS
  Univariate analyses identified statistically significant interactions for age and major VTE (P = 0.09); for both age (P = 0.07) and body weight (P = 0.07) and the outcome of major bleeding; and for creatinine clearance (P = 0.03) and the composite outcome of major and clinically relevant non-major bleeding. Estimates of these possible differences were not precise, with wide 95% confidence intervals (CIs) that included a zero difference for several subgroups. Multivariate logistic regression analysis did not detect a statistically significant interaction for any outcomes.
  
  
  CONCLUSIONS
  This analysis found no convincing evidence that age, weight, gender, BMI or creatinine clearance influenced the balance of benefit to risk for apixaban compared with enoxaparin. Because only 5% of patients had a creatinine clearance between 30 and 50 mL min(-1), further data are needed in such patients.
authors.affiliation: Department of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: G F
authors.initials: GF
authors.lastname: Pineo
authors.forename: A S
authors.initials: AS
authors.lastname: Gallus
authors.forename: G E
authors.initials: GE
authors.lastname: Raskob
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.forename: L-M
authors.initials: LM
authors.lastname: Ramirez
authors.forename: E
authors.initials: E
authors.lastname: Ramacciotti
authors.forename: M R
authors.initials: MR
authors.lastname: Lassen
authors.forename: L
authors.initials: L
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D000367:Age Factors; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects*; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D001835:Body Weight; D016009:Chi-Square Distribution; D017326:Clinical Trials, Phase III as Topic; D003404:Creatinine / Q000097:blood; D004334:Drug Administration Schedule; D017984:Enoxaparin / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects; D011728:Pyridones / Q000008:administration & dosage* / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D017984:Enoxaparin; D005343:Fibrinolytic Agents; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D003404:Creatinine