title: Use of single and combined antithrombotic therapy and risk of serious upper gastrointestinal bleeding: population based case-control study.
abstract: OBJECTIVE
  To assess the risk of serious upper gastrointestinal bleeding associated with the newer antithrombotic agents used alone or in combination with other antithrombotic drugs; to describe the trends in use of antithrombotic drugs in the background population.
  
  
  METHODS
  Population based case-control study.
  
  
  METHODS
  Funen County, Denmark (population 470,000).
  
  
  METHODS
  1443 cases of serious upper gastrointestinal bleeding identified during 2000-4; 57,720 age and sex matched controls.
  
  
  METHODS
  Exposure to low dose aspirin, clopidogrel, dipyridamole, vitamin K antagonists, and combined antithrombotic treatment.
  
  
  RESULTS
  Adjusted odds ratios associating drug use with upper gastrointestinal bleeding were 1.8 (95% confidence interval 1.5 to 2.1) for low dose aspirin, 1.1 (0.6 to 2.1) for clopidogrel, 1.9 (1.3 to 2.8) for dipyridamole, and 1.8 (1.3 to 2.4) for vitamin K antagonists. Corresponding figures for combined use were 7.4 (3.5 to 15) for clopidogrel and aspirin, 5.3 (2.9 to 9.5) for vitamin K antagonists and aspirin, and 2.3 (1.7 to 3.3) for dipyridamole and aspirin. Other combinations were used too infrequently to allow estimation. The number of treatment years needed to produce one excess case varied from 124 for the clopidogrel-aspirin combination to 8800 for clopidogrel alone. During the study period, exposure to combined antithrombotic regimens increased by 425% in the background population.
  
  
  CONCLUSIONS
  Antithrombotic treatment is becoming increasingly aggressive. Combined antithrombotic treatment confers particular risk and is associated with high incidence of gastrointestinal bleeding.
authors.affiliation: Department of Clinical Pharmacology, IST, Syddansk Universitet, 5000 Odense, Denmark. jhallas@health.sdu.dk
authors.forename: Jesper
authors.initials: J
authors.lastname: Hallas
authors.forename: Michael
authors.initials: M
authors.lastname: Dall
authors.forename: Alin
authors.initials: A
authors.lastname: Andries
authors.forename: Birthe Søgaard
authors.initials: BS
authors.lastname: Andersen
authors.forename: Claus
authors.initials: C
authors.lastname: Aalykke
authors.forename: Jane Møller
authors.initials: JM
authors.lastname: Hansen
authors.forename: Morten
authors.initials: M
authors.lastname: Andersen
authors.forename: Annmarie Touborg
authors.initials: AT
authors.lastname: Lassen
mesh_terms: D000368:Aged; D001241:Aspirin / Q000009:adverse effects*; D016022:Case-Control Studies; D004359:Drug Therapy, Combination; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects*; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced*; D006801:Humans; D008297:Male; D010438:Peptic Ulcer Hemorrhage / Q000139:chemically induced; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D013276:Stomach Ulcer / Q000139:chemically induced
chemical_list: D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D001241:Aspirin