title: Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients.
abstract: BACKGROUND
  The efficacy and safety of prolonging prophylaxis for venous thromboembolism in medically ill patients beyond hospital discharge remain uncertain. We hypothesized that extended prophylaxis with apixaban would be safe and more effective than short-term prophylaxis with enoxaparin.
  
  
  METHODS
  In this double-blind, double-dummy, placebo-controlled trial, we randomly assigned acutely ill patients who had congestive heart failure or respiratory failure or other medical disorders and at least one additional risk factor for venous thromboembolism and who were hospitalized with an expected stay of at least 3 days to receive apixaban, administered orally at a dose of 2.5 mg twice daily for 30 days, or enoxaparin, administered subcutaneously at a dose of 40 mg once daily for 6 to 14 days. The primary efficacy outcome was the 30-day composite of death related to venous thromboembolism, pulmonary embolism, symptomatic deep-vein thrombosis, or asymptomatic proximal-leg deep-vein thrombosis, as detected with the use of systematic bilateral compression ultrasonography on day 30. The primary safety outcome was bleeding. All efficacy and safety outcomes were independently adjudicated.
  
  
  RESULTS
  A total of 6528 subjects underwent randomization, 4495 of whom could be evaluated for the primary efficacy outcome--2211 in the apixaban group and 2284 in the enoxaparin group. Among the patients who could be evaluated, 2.71% in the apixaban group (60 patients) and 3.06% in the enoxaparin group (70 patients) met the criteria for the primary efficacy outcome (relative risk with apixaban, 0.87; 95% confidence interval [CI], 0.62 to 1.23; P=0.44). By day 30, major bleeding had occurred in 0.47% of the patients in the apixaban group (15 of 3184 patients) and in 0.19% of the patients in the enoxaparin group (6 of 3217 patients) (relative risk, 2.58; 95% CI, 1.02 to 7.24; P=0.04).
  
  
  CONCLUSIONS
  In medically ill patients, an extended course of thromboprophylaxis with apixaban was not superior to a shorter course with enoxaparin. Apixaban was associated with significantly more major bleeding events than was enoxaparin. (Funded by Bristol-Myers Squibb and Pfizer; ClinicalTrials.gov number, NCT00457002.).
authors.affiliation: Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. sgoldhaber@partners.org
authors.forename: Samuel Z
authors.initials: SZ
authors.lastname: Goldhaber
authors.forename: Alain
authors.initials: A
authors.lastname: Leizorovicz
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Kakkar
authors.forename: Sylvia K
authors.initials: SK
authors.lastname: Haas
authors.forename: Geno
authors.initials: G
authors.lastname: Merli
authors.forename: Robert M
authors.initials: RM
authors.lastname: Knabb
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Weitz
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D017984:Enoxaparin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D006760:Hospitalization; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011655:Pulmonary Embolism / Q000401:mortality / Q000517:prevention & control; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D011728:Pyridones / Q000009:adverse effects / Q000627:therapeutic use*; D012131:Respiratory Insufficiency / Q000188:drug therapy; D012307:Risk Factors; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban