title: Oral anticoagulant and antiplatelet therapy and peripheral arterial disease.
abstract: BACKGROUND
  Atherosclerotic peripheral arterial disease is associated with an increased risk of myocardial infarction, stroke, and death from cardiovascular causes. Antiplatelet drugs reduce this risk, but the role of oral anticoagulant agents in the prevention of cardiovascular complications in patients with peripheral arterial disease is unclear.
  
  
  METHODS
  We assigned patients with peripheral arterial disease to combination therapy with an antiplatelet agent and an oral anticoagulant agent (target international normalized ratio [INR], 2.0 to 3.0) or to antiplatelet therapy alone. The first coprimary outcome was myocardial infarction, stroke, or death from cardiovascular causes; the second coprimary outcome was myocardial infarction, stroke, severe ischemia of the peripheral or coronary arteries leading to urgent intervention, or death from cardiovascular causes.
  
  
  RESULTS
  A total of 2161 patients were randomly assigned to therapy. The mean follow-up time was 35 months. Myocardial infarction, stroke, or death from cardiovascular causes occurred in 132 of 1080 patients receiving combination therapy (12.2%) and in 144 of 1081 patients receiving antiplatelet therapy alone (13.3%) (relative risk, 0.92; 95% confidence interval [CI], 0.73 to 1.16; P=0.48). Myocardial infarction, stroke, severe ischemia, or death from cardiovascular causes occurred in 172 patients receiving combination therapy (15.9%) as compared with 188 patients receiving antiplatelet therapy alone (17.4%) (relative risk, 0.91; 95% CI, 0.74 to 1.12; P=0.37). Life-threatening bleeding occurred in 43 patients receiving combination therapy (4.0%) as compared with 13 patients receiving antiplatelet therapy alone (1.2%) (relative risk, 3.41; 95% CI, 1.84 to 6.35; P<0.001).
  
  
  CONCLUSIONS
  In patients with peripheral arterial disease, the combination of an oral anticoagulant and antiplatelet therapy was not more effective than antiplatelet therapy alone in preventing major cardiovascular complications and was associated with an increase in life-threatening bleeding. (ClinicalTrials.gov number, NCT00125671 [ClinicalTrials.gov].).
authors.affiliation: McMaster University, Hamilton, ON, Canada. anands@mcmaster.ca
authors.forename: Sonia
authors.initials: S
authors.lastname: Anand
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.forename: Changchun
authors.initials: C
authors.lastname: Xie
authors.forename: Janice
authors.initials: J
authors.lastname: Pogue
authors.forename: John
authors.initials: J
authors.lastname: Eikelboom
authors.forename: Andrzej
authors.initials: A
authors.lastname: Budaj
authors.forename: Bruce
authors.initials: B
authors.lastname: Sussex
authors.forename: Lisheng
authors.initials: L
authors.lastname: Liu
authors.forename: Randy
authors.initials: R
authors.lastname: Guzman
authors.forename: Claudio
authors.initials: C
authors.lastname: Cina
authors.forename: Richard
authors.initials: R
authors.lastname: Crowell
authors.forename: Matyas
authors.initials: M
authors.lastname: Keltai
authors.forename: Gilbert
authors.initials: G
authors.lastname: Gosselin
mesh_terms: D000074:Acenocoumarol / Q000627:therapeutic use; D000284:Administration, Oral; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use; D050197:Atherosclerosis / Q000188:drug therapy*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced / Q000401:mortality; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D014859:Warfarin; D000077144:Clopidogrel; D000074:Acenocoumarol; D013988:Ticlopidine; D001241:Aspirin