title: Design of the blockade of the glycoprotein IIb/IIIa receptor to avoid vascular occlusion (BRAVO) trial.
abstract: BACKGROUND
  Platelets play a key role in the pathogenesis of atherosclerosis, thrombosis, and acute coronary and cerebrovascular syndromes. Inhibition of platelet function by acetylsalicylic acid (aspirin) has been shown to reduce the incidence atherothrombotic events in patients with coronary, cerebrovascular, or peripheral vascular disease. Thienopyridine agents, however, including ticlopidine and clopidogrel, inhibit the adenosine diphosphate receptor and have modestly superior effects compared with aspirin on reduction of death, myocardial infarction, and stroke among a broad group of patients with vascular disease. More effective antithrombotic agents are still required to treat patients at high risk for recurrent vascular events.
  
  
  METHODS
  Lotrafiban, a selective, nonpeptide antagonist of the human platelet fibrinogen receptor (glycoprotein [GP] IIb/IIIa [alphaIIb/beta3 integrin]), blocks the binding of fibrinogen to the GP IIb/IIIa receptor, which is the final common pathway of platelet aggregation. Lotrafiban at doses of up to 50 mg twice daily was well-tolerated in a 12-week, double-blind, placebo-controlled, dose-ranging study in patients with recent myocardial infarction, unstable angina, transient ischemic attack, or stroke when added to aspirin therapy. On the basis of these results, a dosing regimen was selected for the phase III Blockage of the Glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion (BRAVO) trial based on pharmacodynamics and drug tolerability. In the pivotal BRAVO study, lotrafiban therapy is being evaluated in patients who have had a recent myocardial infarction, unstable angina, transient ischemic attack, or ischemic stroke, or who present at any time after a diagnosis of peripheral vascular disease combined with either cardiovascular or cerebrovascular disease.
  
  
  RESULTS
  The efficacy evaluation will be based on a composite end point of clinical events (death by any cause, myocardial infarction, stroke, recurrent ischemia requiring hospitalization, or urgent ischemia-driven revascularization). The target enrollment is 9200 patients worldwide. Approximately 700 centers will participate and will be distributed within 30 countries across North America, Europe, Australia, and Asia.
authors.affiliation: Department of Cardiology, The Cleveland Clinic Foundation, OH 44195, USA. topole@ccf.org
authors.forename: E J
authors.initials: EJ
authors.lastname: Topol
authors.forename: J D
authors.initials: JD
authors.lastname: Easton
authors.forename: P
authors.initials: P
authors.lastname: Amarenco
authors.forename: R
authors.initials: R
authors.lastname: Califf
authors.forename: R
authors.initials: R
authors.lastname: Harrington
authors.forename: C
authors.initials: C
authors.lastname: Graffagnino
authors.forename: S
authors.initials: S
authors.lastname: Davis
authors.forename: H C
authors.initials: HC
authors.lastname: Diener
authors.forename: J
authors.initials: J
authors.lastname: Ferguson
authors.forename: D
authors.initials: D
authors.lastname: Fitzgerald
authors.forename: A
authors.initials: A
authors.lastname: Shuaib
authors.forename: P J
authors.initials: PJ
authors.lastname: Koudstaal
authors.forename: P
authors.initials: P
authors.lastname: Theroux
authors.forename: F
authors.initials: F
authors.lastname: Van de Werf
authors.forename: J T
authors.initials: JT
authors.lastname: Willerson
authors.forename: R
authors.initials: R
authors.lastname: Chan
authors.forename: R
authors.initials: R
authors.lastname: Samuels
authors.forename: B
authors.initials: B
authors.lastname: Ilson
authors.forename: J
authors.initials: J
authors.lastname: Granett
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D001157:Arterial Occlusive Diseases / Q000097:blood / Q000517:prevention & control*; D001569:Benzodiazepines; D004311:Double-Blind Method; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D002546:Ischemic Attack, Transient / Q000097:blood / Q000188:drug therapy*; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000097:blood / Q000188:drug therapy*; D010880:Piperidines; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012107:Research Design; D055502:Secondary Prevention; D020521:Stroke / Q000097:blood / Q000517:prevention & control
chemical_list: D010880:Piperidines; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D001569:Benzodiazepines; C412702:lotrafiban