title: Comparative risk of major bleeding with new oral anticoagulants (NOACs) and phenprocoumon in patients with atrial fibrillation: a post-marketing surveillance study.
abstract: BACKGROUND
  Non-vitamin K antagonist oral anticoagulants (NOACs) are at least as effective and safe as vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF). All pivotal trials have compared NOACs to warfarin. However, other VKAs are commonly used, for instance phenprocoumon.
  
  
  METHODS
  A retrospective cohort study using a German claims database assessed the comparative risks of bleeding leading to hospitalization during therapy with NOACs and phenprocoumon in AF patients. Endpoints consisted of major bleeding, gastrointestinal bleeding, and any bleeding. Data were collected from January 1, 2013 to March 31, 2015. Patients newly initiated on dabigatran, apixaban, rivaroxaban, or phenprocoumon were included. Hazard Ratios for bleeding events were derived from Cox proportional hazard models, adjusting for differences in baseline characteristics. Propensity score matching was performed as a sensitivity analysis.
  
  
  RESULTS
  A total of 35,013 patients were identified, including 3138 on dabigatran, 3633 on apixaban, 12,063 on rivaroxaban, and 16,179 on phenprocoumon. Patients prescribed apixaban or phenprocoumon were older compared to those on dabigatran or rivaroxaban and had a higher CHA2DS2-VASc score. After adjusting for baseline confounders, apixaban was associated with lower risks of major bleeding (HR 0.68, 95% CI 0.51-0.90, p = 0.008), gastrointestinal bleeding (HR 0.53, 95% CI 0.39-0.72, p < 0.001), and any bleeding (HR 0.80, 95% CI 0.70-0.92, p = 0.002) compared to phenprocoumon. There were no significant differences in bleeding risk between dabigatran and phenprocoumon. Rivaroxaban was associated with more gastrointestinal bleeding (HR 1.39, 95% CI 1.21-1.60, p < 0.001) and any bleeding (HR 1.19, 95% CI 1.10-1.28, p < 0.001). Sensitivity analysis using propensity score matching confirmed these observations.
  
  
  CONCLUSIONS
  Apixaban therapy is associated with a significantly reduced risk of bleeding compared to phenprocoumon. Bleeding risk with dabigatran was similar to that of phenprocoumon but bleeding risk with rivaroxaban was higher.
authors.affiliation: Division Clinical Electrophysiology, Department of Cardiology, Johann Wolfgang Goethe University, Frankfurt, Germany. Hohnloser@em.uni-frankfurt.de.
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Hohnloser
authors.affiliation: Pfizer Deutschland GmbH, Berlin, Germany.
authors.forename: Edin
authors.initials: E
authors.lastname: Basic
authors.affiliation: Department of Cardiology, Ludwig Maximilians University, Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Nabauer
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000150:complications* / Q000188:drug therapy; D005260:Female; D005500:Follow-Up Studies; D005858:Germany / Q000453:epidemiology; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D010644:Phenprocoumon / Q000008:administration & dosage / Q000009:adverse effects*; D011358:Product Surveillance, Postmarketing / Q000379:methods*; D012189:Retrospective Studies; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D010644:Phenprocoumon
keywords: Apixaban; Atrial fibrillation; Dabigatran; Major bleeding; Phenprocoumon; Rivaroxaban