title: Known knowns and known unknowns: risks associated with combination antithrombotic therapy.
abstract: BACKGROUND
  Use of antiplatelet therapy in combination with oral anticoagulants remains controversial. The purpose of this article is to review current consensus recommendations for antithrombotic therapy, to evaluate risks for bleeding among patients taking combination antithrombotic therapy, and lastly to review single-center data from Kaiser Permanente Colorado detailing clinical outcomes associated with combination therapy.
  
  
  METHODS
  This was a retrospective, longitudinal pharmacoepidemiologic review. Adult patients receiving warfarin managed by a clinical pharmacy service who had documented antiplatelet (aspirin, clopidogrel, and/or dipyridamole) use (combination therapy cohort) or non-use (monotherapy cohort) were identified as of September 30, 2005. Utilizing integrated, electronic medical records, anticoagulation-related adverse events (death, hemorrhage, thrombosis) and coronary events were identified during a six-month follow-up (October 2005 through March 2006). Proportions of events were compared between cohorts. Independent associations between the cohorts and the outcomes were assessed with adjustment for potential confounding factors.
  
  
  RESULTS
  Data from 2,560 monotherapy and 1,623 combination therapy patients were analyzed. Patients in the combination therapy cohort were more likely to have had anticoagulation-related hemorrhages (4.2% vs. 2.0%, unadjusted p<0.001). With adjustment, combined warfarin and antiplatelet use was independently associated with hemorrhagic (OR=2.75; 95% CI 1.44, 5.28) but not coronary (OR=0.99; 95% CI 0.37, 2.62) events.
  
  
  CONCLUSIONS
  At the population level, the hemorrhagic risk associated with warfarin therapy combined with antiplatelet therapy appears to outweigh the benefits. These findings suggest that clinicians carefully consider risks and benefits when prescribing antiplatelet therapy for patients taking warfarin who do not meet evidence-based criteria for that approach.
authors.affiliation: Clinical Pharmacy Services, Rock Creek Medical Center, Kaiser Permanente Colorado, Denver, CO, USA. samuel.g.johnson@kp.org
authors.forename: S
authors.initials: S
authors.lastname: Johnson
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies; D012307:Risk Factors; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D014859:Warfarin