title: Apixaban for extended treatment of venous thromboembolism.
abstract: Apixaban, an oral factor Xa inhibitor that can be administered in a simple, fixed-dose regimen, may be an option for the extended treatment of venous thromboembolism.
  
  
  
  In this randomized, double-blind study, we compared two doses of apixaban (2.5 mg and 5 mg, twice daily) with placebo in patients with venous thromboembolism who had completed 6 to 12 months of anticoagulation therapy and for whom there was clinical equipoise regarding the continuation or cessation of anticoagulation therapy. The study drugs were administered for 12 months.
  
  
  
  A total of 2486 patients underwent randomization, of whom 2482 were included in the intention-to-treat analyses. Symptomatic recurrent venous thromboembolism or death from venous thromboembolism occurred in 73 of the 829 patients (8.8%) who were receiving placebo, as compared with 14 of the 840 patients (1.7%) who were receiving 2.5 mg of apixaban (a difference of 7.2 percentage points; 95% confidence interval [CI], 5.0 to 9.3) and 14 of the 813 patients (1.7%) who were receiving 5 mg of apixaban (a difference of 7.0 percentage points; 95% CI, 4.9 to 9.1) (P<0.001 for both comparisons). The rates of major bleeding were 0.5% in the placebo group, 0.2% in the 2.5-mg apixaban group, and 0.1% in the 5-mg apixaban group. The rates of clinically relevant nonmajor bleeding were 2.3% in the placebo group, 3.0% in the 2.5-mg apixaban group, and 4.2% in the 5-mg apixaban group. The rate of death from any cause was 1.7% in the placebo group, as compared with 0.8% in the 2.5-mg apixaban group and 0.5% in the 5-mg apixaban group.
  
  
  
  Extended anticoagulation with apixaban at either a treatment dose (5 mg) or a thromboprophylactic dose (2.5 mg) reduced the risk of recurrent venous thromboembolism without increasing the rate of major bleeding. (Funded by Bristol-Myers Squibb and Pfizer; AMPLIFY-EXT ClinicalTrials.gov number, NCT00633893.).
authors.affiliation: Department of Internal and Cardiovascular Medicine-Stroke Unit, University of Perugia, Perugia, Italy. agnellig@unipg.it
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Agnelli
authors.forename: Harry R
authors.initials: HR
authors.lastname: Buller
authors.forename: Alexander
authors.initials: A
authors.lastname: Cohen
authors.forename: Madelyn
authors.initials: M
authors.lastname: Curto
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Gallus
authors.forename: Margot
authors.initials: M
authors.lastname: Johnson
authors.forename: Anthony
authors.initials: A
authors.lastname: Porcari
authors.forename: Gary E
authors.initials: GE
authors.lastname: Raskob
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Weitz
mesh_terms: D000328:Adult; D000368:Aged; D003404:Creatinine / Q000378:metabolism; D004311:Double-Blind Method; D065427:Factor Xa Inhibitors; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D057194:Intention to Treat Analysis; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D011728:Pyridones / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D012008:Recurrence; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000188:drug therapy* / Q000401:mortality
chemical_list: D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D003404:Creatinine