title: Polypharmacy is associated with an increased risk of bleeding in elderly patients with venous thromboembolism.
abstract: BACKGROUND
  Polypharmacy, defined as the concomitant use of multiple medications, is very common in the elderly and may trigger drug-drug interactions and increase the risk of falls in patients receiving vitamin K antagonists.
  
  
  OBJECTIVE
  To examine whether polypharmacy increases the risk of bleeding in elderly patients who receive vitamin K antagonists for acute venous thromboembolism (VTE).
  
  
  METHODS
  We used a prospective cohort study.
  
  
  METHODS
  In a multicenter Swiss cohort, we studied 830 patients aged ≥ 65 years with VTE.
  
  
  METHODS
  We defined polypharmacy as the prescription of more than four different drugs. We assessed the association between polypharmacy and the time to a first major and clinically relevant non-major bleeding, accounting for the competing risk of death. We adjusted for known bleeding risk factors (age, gender, pulmonary embolism, active cancer, arterial hypertension, cardiac disease, cerebrovascular disease, chronic liver and renal disease, diabetes mellitus, history of major bleeding, recent surgery, anemia, thrombocytopenia) and periods of vitamin K antagonist treatment as a time-varying covariate.
  
  
  RESULTS
  Overall, 413 (49.8 %) patients had polypharmacy. The mean follow-up duration was 17.8 months. Patients with polypharmacy had a significantly higher incidence of major (9.0 vs. 4.1 events/100 patient-years; incidence rate ratio [IRR] 2.18, 95 % confidence interval [CI] 1.32-3.68) and clinically relevant non-major bleeding (14.8 vs. 8.0 events/100 patient-years; IRR 1.85, 95 % CI 1.27-2.71) than patients without polypharmacy. After adjustment, polypharmacy was significantly associated with major (sub-hazard ratio [SHR] 1.83, 95 % CI 1.03-3.25) and clinically relevant non-major bleeding (SHR 1.60, 95 % CI 1.06-2.42).
  
  
  CONCLUSIONS
  Polypharmacy is associated with an increased risk of both major and clinically relevant non-major bleeding in elderly patients receiving vitamin K antagonists for VTE.
authors.affiliation: Department of General Internal Medicine, Bern University Hospital, Bern, Switzerland, Waltraud.Leiss@Insel.ch.
authors.forename: Waltraud
authors.initials: W
authors.lastname: Leiss
authors.forename: Marie
authors.initials: M
authors.lastname: Méan
authors.forename: Andreas
authors.initials: A
authors.lastname: Limacher
authors.forename: Marc
authors.initials: M
authors.lastname: Righini
authors.forename: Kurt
authors.initials: K
authors.lastname: Jaeger
authors.forename: Hans-Jürg
authors.initials: HJ
authors.lastname: Beer
authors.forename: Joseph
authors.initials: J
authors.lastname: Osterwalder
authors.forename: Beat
authors.initials: B
authors.lastname: Frauchiger
authors.forename: Christian M
authors.initials: CM
authors.lastname: Matter
authors.forename: Nils
authors.initials: N
authors.lastname: Kucher
authors.forename: Anne
authors.initials: A
authors.lastname: Angelillo-Scherrer
authors.forename: Jacques
authors.initials: J
authors.lastname: Cornuz
authors.forename: Martin
authors.initials: M
authors.lastname: Banyai
authors.forename: Bernhard
authors.initials: B
authors.lastname: Lämmle
authors.forename: Marc
authors.initials: M
authors.lastname: Husmann
authors.forename: Michael
authors.initials: M
authors.lastname: Egloff
authors.forename: Markus
authors.initials: M
authors.lastname: Aschwanden
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rodondi
authors.forename: Drahomir
authors.initials: D
authors.lastname: Aujesky
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D019338:Polypharmacy; D011446:Prospective Studies; D012307:Risk Factors; D013557:Switzerland / Q000453:epidemiology; D054556:Venous Thromboembolism / Q000188:drug therapy* / Q000453:epidemiology; D014812:Vitamin K / Q000037:antagonists & inhibitors
chemical_list: D000925:Anticoagulants; D014812:Vitamin K