title: Recombinant nematode anticoagulant protein c2, an inhibitor of the tissue factor/factor VIIa complex, in patients undergoing elective coronary angioplasty.
abstract: OBJECTIVE
  We investigated the safety and pharmacodynamics of escalating doses of recombinant nematode anticoagulant protein c2 (rNAPc2) in patients undergoing elective coronary angioplasty.
  
  
  BACKGROUND
  Recombinant NAPc2 is a potent inhibitor of the tissue factor/factor VIIa complex, which has the potential to reduce the risk of thrombotic complications in coronary artery disease.
  
  
  METHODS
  In a randomized, double-blinded, dose-escalation, multicenter trial, 154 patients received placebo or rNAPc2 at doses of 3.5, 5.0, 7.5, and 10.0 microg/kg body weight as a single subcutaneous administration 2 to 6 h before angioplasty. All patients received aspirin, unfractionated heparin during angioplasty, and clopidogrel in case of stent implantation.
  
  
  RESULTS
  Minor bleeding rates for the doses 3.5 to 7.5 microg/kg were comparable to that with placebo (6.7%), whereas an incidence of 26.9% was observed at the 10.0 microg/kg dose level (p < 0.01). Major bleedings occurred in the 5.0 microg/kg (n = 3) and 7.5 microg/kg (n = 1) dose groups. The three patients in the 5.0 microg/kg dose group also received a glycoprotein IIb/IIIa receptor inhibitor at the moment of major bleeding. Systemic thrombin generation, as measured by prothrombin fragment 1+2 (F(1+2)), was suppressed in all rNAPc2 dose groups to levels below pretreatment values for at least 36 h. In the placebo group, a distinct increase of F(1+2) levels was observed following cessation of heparin.
  
  
  CONCLUSIONS
  Inhibition of the tissue factor/factor VIIa complex with rNAPc2, at doses up to 7.5 microg/kg, in combination with aspirin, clopidogrel, and unfractionated heparin appears to be a safe and effective strategy to prevent thrombin generation during coronary angioplasty.
authors.affiliation: Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands. A. H. Moons@amc.uva.nl
authors.forename: Arno H M
authors.initials: AH
authors.lastname: Moons
authors.forename: Ron J G
authors.initials: RJ
authors.lastname: Peters
authors.forename: Nick R
authors.initials: NR
authors.lastname: Bijsterveld
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Piek
authors.forename: Martin H
authors.initials: MH
authors.lastname: Prins
authors.forename: George P
authors.initials: GP
authors.lastname: Vlasuk
authors.forename: William E
authors.initials: WE
authors.lastname: Rote
authors.forename: Harry R
authors.initials: HR
authors.lastname: Büller
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D023921:Coronary Stenosis / Q000628:therapy*; D003328:Coronary Thrombosis / Q000209:etiology* / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D017558:Elective Surgical Procedures / Q000009:adverse effects; D015942:Factor VIIa / Q000037:antagonists & inhibitors* / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D015801:Helminth Proteins / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D013925:Thromboplastin / Q000037:antagonists & inhibitors* / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D015801:Helminth Proteins; C400226:anti-coagulant protein C2, Ancylostoma caninum; D013925:Thromboplastin; D015942:Factor VIIa