title: Efficacy and safety of dabigatran etexilate and warfarin in "real-world" patients with atrial fibrillation: a prospective nationwide cohort study.
abstract: OBJECTIVE
  The aim of this study was to assess the efficacy and safety in an "everyday clinical practice" population of anticoagulant-naïve patients with atrial fibrillation (AF) treated with dabigatran etexilate after its post-approval availability in Denmark, compared with warfarin.
  
  
  BACKGROUND
  Concerns have been raised about an excess of bleeding events or myocardial infarction (MI) among patients treated with the new oral direct thrombin inhibitor, dabigatran etexilate.
  
  
  METHODS
  From the Danish Registry of Medicinal Product Statistics, we identified a dabigatran-treated group and a 1:2 propensity-matched warfarin-treated group of 4,978 and 8,936, respectively. Comparisons on efficacy and safety outcomes were made on the basis of Cox-proportional hazards models stratified on propensity-matched groups.
  
  
  RESULTS
  Stroke and systemic embolism were not significantly different between warfarin- and dabigatran-treated patients. Adjusted mortality was significantly lower with both dabigatran doses (110 mg b.i.d., propensity-match group stratified hazard ratio [aHR]: 0.79, 95% confidence interval [CI]: 0.65 to 0.95; 150 mg b.i.d., aHR: 0.57, 95% CI: 0.40 to 0.80), when compared with warfarin. Pulmonary embolism was lower compared with warfarin for both doses of dabigatran. Less intracranial bleeding was seen with both dabigatran doses (110 mg b.i.d., aHR: 0.24, 95% CI: 0.08 to 0.56; 150 mg b.i.d., aHR: 0.08, 95% CI: 0.01 to 0.40). The incidence of MI was lower with both dabigatran doses (110 mg b.i.d., aHR: 0.30, 95% CI: 0.18 to 0.49; 150 mg b.i.d., aHR: 0.40, 95% CI: 0.21 to 0.70). Gastrointestinal bleeding was lower with dabigatran 110 mg b.i.d. (aHR: 0.60, 95% CI: 0.37 to 0.93) compared with warfarin but not dabigatran 150 mg b.i.d. The main findings were broadly consistent in a subgroup analysis of dabigatran users with ≥1-year follow-up (median follow-up 13.9 months [interquartile range: 12.6 to 15.3 months]).
  
  
  CONCLUSIONS
  In this "everyday clinical practice" post-approval nationwide clinical cohort, there were similar stroke/systemic embolism and major bleeding rates with dabigatran (both doses) compared with warfarin. Mortality, intracranial bleeding, pulmonary embolism, and MI were lower with dabigatran, compared with warfarin. We found no evidence of an excess of bleeding events or MI among dabigatran-treated patients in this propensity-matched comparison against warfarin, even in the subgroup with ≥1-year follow-up.
authors.affiliation: Department of Cardiology, Cardiovascular Research Centre, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Torben Bjerregaard
authors.initials: TB
authors.lastname: Larsen
authors.forename: Lars Hvilsted
authors.initials: LH
authors.lastname: Rasmussen
authors.forename: Flemming
authors.initials: F
authors.lastname: Skjøth
authors.forename: Karen Margrete
authors.initials: KM
authors.lastname: Due
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Callréus
authors.forename: Mary
authors.initials: M
authors.lastname: Rosenzweig
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use*; D000991:Antithrombins / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000453:epidemiology; D001562:Benzimidazoles / Q000627:therapeutic use*; D000069604:Dabigatran; D003718:Denmark / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D005260:Female; D005500:Follow-Up Studies; D006471:Gastrointestinal Hemorrhage / Q000453:epidemiology; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D015994:Incidence; D020300:Intracranial Hemorrhages / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D009203:Myocardial Infarction / Q000453:epidemiology; D057216:Propensity Score; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011655:Pulmonary Embolism / Q000453:epidemiology; D011725:Pyridines / Q000627:therapeutic use*; D012042:Registries; D020521:Stroke / Q000453:epidemiology; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D001562:Benzimidazoles; D011725:Pyridines; D014859:Warfarin; D000069604:Dabigatran