title: The constitutive procoagulant and hypofibrinolytic state in patients with intermittent claudication due to infrainguinal disease significantly improves with percutaneous transluminal balloon angioplasty.
abstract: BACKGROUND
  Patients with intermittent lower limb claudication (IC) exhibit a prothrombotic diathesis that is acutely exacerbated by exercise. This may occur because of ischemia/reperfusion injury within the leg muscles during walking and may contribute to the increased risk of thrombotic vascular events in this group of patients. This randomized study compared the effect of lower limb revascularization by percutaneous transluminal balloon angioplasty (PTA), supervised exercise, and best medical therapy (BMT) alone on this prothrombotic state.
  
  
  METHODS
  Twenty-three patients (16 men and 7 women; median age, 67 years; range, 57-77 years) with IC due to infrainguinal disease were randomized to receive BMT alone (n = 7), BMT plus PTA (n = 9), or BMT plus supervised exercise (n = 7) as part of the Health Technology Assessment-funded EXercise vs Angioplasty in Claudication Trial (EXACT). Patients were assessed at baseline and at 3 and 6 months. Thrombin-antithrombin complex (TAT) was determined as a marker of thrombin generation, and plasminogen activator inhibitor (PAI) antigen was determined as a marker of fibrinolysis. Increased TAT indicates a procoagulant state, and increased PAI antigen indicates a hypofibrinolytic state.
  
  
  RESULTS
  At 6 months, subjects randomized to BMT plus PTA demonstrated a significant improvement in ankle-brachial pressure index (P = .013) and maximal walking distance (P = .008), a significant decline in resting thrombin generation (median [interquartile range] TAT, 6.4 microg/L [2.7-13.5 microg/L] to 1.5 microg/L [0.3-2.9 microg/L]; P = .038), and an improvement in resting fibrinolysis (median [interquartile range] PAI-1, 10.0 ng/mL [1.0-20.5 ng/mL] to 1.0 ng/mL [1.0-14.8 ng/mL]; P = .043). There was no significant change in any of these parameters in patients randomized to BMT plus supervised exercise or to BMT alone.
  
  
  CONCLUSIONS
  The addition of lower limb revascularization by PTA to BMT in patients with IC due to infra-inguinal disease results in a medium-term improvement in the resting procoagulant and hypofibrinolytic state. This may translate into a reduction in morbidity and mortality from thrombotic vascular events in this group of patients.
authors.affiliation: University Department of Vascular Surgery, Heart of England NHS Foundation Trust, Birmingham, UK. simon@hobbsy.fsworld.co.uk
authors.forename: Simon D
authors.initials: SD
authors.lastname: Hobbs
authors.forename: Tim
authors.initials: T
authors.lastname: Marshall
authors.forename: Chris
authors.initials: C
authors.lastname: Fegan
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Adam
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Bradbury
mesh_terms: D000368:Aged; D000800:Angioplasty, Balloon; D000990:Antithrombin III; D001777:Blood Coagulation; D005081:Exercise Therapy; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D007383:Intermittent Claudication / Q000097:blood* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000097:blood*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D010447:Peptide Hydrolases