title: A safety and feasibility report of combined direct thrombin and GP IIb/IIIa inhibition with bivalirudin and tirofiban in peripheral vascular disease intervention: treating critical limb ischemia like acute coronary syndrome.
abstract: BACKGROUND
  The combination of glycoprotein (GP) IIb-IIIa inhibition and direct thrombin inhibition (DTI) with bivalirudin (Angiomax, The Medicines Company, Cambridge, Massachusetts) have shown ischemic and hemorrhagic outcomes benefit in coronary interventions and may have similar benefits in percutaneous peripheral interventions (PPI). The high incidence of diabetes, chronic renal disease, platelet dysfunction, hypercoagulability, inflammation and a thrombus-rich environment make a GP IIb-IIIa and DTI combination with tirofiban (Aggrastat Merck and Company, Inc., Whitehouse Station, New Jersey) an attractive anticoagulation strategy in the PPI treatment of critical limb ischemia (CLI).
  
  
  METHODS
  Between May 1, 2001 and January 31, 2003, a CLI treatment group of 149 patients received PPI with bivalirudin (0.75 mg per kg bolus with 1.75 mg per kg per hour periprocedural infusion) and tirofiban (10 mcg per kg per minute bolus with 12-hour 0.1 mcg per kg per minute infusion) as an anticoagulation and antiplatelet strategy, and were compared to a matched unfractionated heparin (UFH) control group without GP IIb-IIIa inhibitors. Clinical and hemostasis outcomes were analyzed, including distal embolization (DE).
  
  
  RESULTS
  Procedural success was 95.9% and 97.3% in the UFH control group and DTI-GP IIb-IIIa group, respectively. Significant differences were observed in the sheath removal time < 2 hours (60.5% UFH group versus 19.4% DTI-GP IIb-IIIa group; p = < 0.0001). Vascular closure devices were used equally in both groups. No statistical significance was observed in major and minor complications, femoral access complications, acute (< 48 hours) or subacute (30 days) vessel thrombosis, and 6-month duplex ultrasound restenosis rate between the DTI-GP IIb-IIIa versus the UFH group. A trend towards statistical significance was observed in the 6-month secondary re-intervention and limb salvage rates (10.7% versus 18.8%; p = 0.0501 and 93.9% versus 88.5%; p = 0.053) in the DTI-GP IIb-IIIa versus the UFH group, respectively. Angiographically relevant DE occurred in 4 of 149 (1.3%) and 8 of 149 (5.4%) of the bivalirudin-tirofiban and UFH groups, respectively.
  
  
  CONCLUSIONS
  The combination of DTI with bivalirudin and GP IIb-IIIa inhibition with tirofiban is a safe and feasible alternative anticoagulation and antiplatelet strategy in PPI, and may offer improved clinical and hemostasis outcomes in treating CLI. A larger, prospective randomized trial is warranted.
authors.affiliation: Cardiovascular Institute of the South, Houma, LA, USA. david.allie@cardio.com
authors.forename: David E
authors.initials: DE
authors.lastname: Allie
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Hebert
authors.forename: Mitchell D
authors.initials: MD
authors.lastname: Lirtzman
authors.forename: Charles H
authors.initials: CH
authors.lastname: Wyatt
authors.forename: V Antoine
authors.initials: VA
authors.lastname: Keller
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Khan
authors.forename: Muhammad A
authors.initials: MA
authors.lastname: Khan
authors.forename: Peter S
authors.initials: PS
authors.lastname: Fail
authors.forename: Krishnamoorthy
authors.initials: K
authors.lastname: Vivekananthan
authors.forename: Sonja E
authors.initials: SE
authors.lastname: Allie
authors.forename: Elena V
authors.initials: EV
authors.lastname: Mitran
authors.forename: Gary
authors.initials: G
authors.lastname: Chaisson
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Stagg
authors.forename: Adam A
authors.initials: AA
authors.lastname: Allie
authors.forename: Michael W
authors.initials: MW
authors.lastname: McElderry
authors.forename: Esmond A
authors.initials: EA
authors.lastname: Barker
authors.forename: Craig M
authors.initials: CM
authors.lastname: Walker
mesh_terms: D000208:Acute Disease; D000368:Aged; D000800:Angioplasty, Balloon; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006629:Hirudins; D006801:Humans; D007511:Ischemia / Q000097:blood / Q000628:therapy; D007866:Leg / Q000098:blood supply; D008297:Male; D017202:Myocardial Ischemia / Q000097:blood / Q000628:therapy; D010446:Peptide Fragments / Q000627:therapeutic use*; D016491:Peripheral Vascular Diseases / Q000097:blood / Q000628:therapy*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077466:Tirofiban; D016896:Treatment Outcome; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D006629:Hirudins; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; D014443:Tyrosine; D013917:Thrombin; D000077466:Tirofiban; C074619:bivalirudin