title: Bleeding increases the risk of ischemic events in patients with peripheral arterial disease.
abstract: BACKGROUND
  Patients with peripheral arterial disease are at high risk of ischemic events and therefore are treated with antithrombotics. In patients with coronary artery disease or cerebrovascular disease, bleeding is related to the subsequent occurrence of ischemic events. Our objective was to assess whether this is also the case in patients with peripheral arterial disease.
  
  
  RESULTS
  All patients from the Dutch Bypass and Oral Anticoagulants or Aspirin (BOA) Study, a multicenter randomized trial comparing oral anticoagulants with aspirin after infrainguinal bypass surgery, were included. The primary outcome event was the composite of nonfatal myocardial infarction, nonfatal ischemic stroke, major amputation, and cardiovascular death. To identify major bleeding as an independent predictor for ischemic events, crude and adjusted hazard ratios with 95% confidence intervals were calculated with multivariable Cox regression models. From 1995 until 1998, 2650 patients were included with 101 nonfatal major bleedings. During a mean follow-up of 14 months, the primary outcome event occurred in 218 patients; 22 events were preceded by a major bleeding. The mean time between major bleeding and the primary outcome event was 4 months. Major bleeding was associated with a 3-fold increased risk of subsequent ischemic events (crude hazard ratio, 3.0; 95% confidence interval, 1.9 to 4.6; adjusted hazard ratio, 3.0; 95% confidence interval, 1.9 to 4.7).
  
  
  CONCLUSIONS
  In patients with peripheral arterial disease, as in patients with coronary artery disease or cerebrovascular disease, major bleeding was independently associated with major ischemic complications. Without compromising the benefits of antithrombotics, these findings call for caution relative to the risks of major bleeding.
authors.affiliation: Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, the Netherlands. e.vanhattum@umcutrecht.nl
authors.forename: Eline S
authors.initials: ES
authors.lastname: van Hattum
authors.forename: Ale
authors.initials: A
authors.lastname: Algra
authors.forename: James A
authors.initials: JA
authors.lastname: Lawson
authors.forename: Bert C
authors.initials: BC
authors.lastname: Eikelboom
authors.forename: Frans L
authors.initials: FL
authors.lastname: Moll
authors.forename: Marco J D
authors.initials: MJ
authors.lastname: Tangelder
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D002543:Cerebral Hemorrhage / Q000139:chemically induced; D016001:Confidence Intervals; D005260:Female; D005500:Follow-Up Studies; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced; D006119:Groin / Q000098:blood supply; D006470:Hemorrhage / Q000139:chemically induced* / Q000150:complications* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007511:Ischemia / Q000209:etiology*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000188:drug therapy* / Q000601:surgery; D011182:Postoperative Care; D016016:Proportional Hazards Models; D012307:Risk Factors
chemical_list: D000925:Anticoagulants; D001241:Aspirin