Design of the blockade of the glycoprotein IIb/IIIa receptor to avoid vascular occlusion (BRAVO) trial

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 re duce the incidence atherothrombotic events in patients with coronary, cereb rovascular, or peripheral vascular disease. Thienopyridine agents, however, including ticlopidine and clopidogrel, inhibit the adenosine diphosphate r eceptor and have modestly superior effects compared with aspirin on reducti on of death, myocardial infarction, and stroke among a brood group of patie nts with vascular disease. More effective antithrombotic agents are still r equired to treat patients at high risk for recurrent vascular events. Methods lotrafiban, a selective, nonpeptide antagonist of the human platele t fibrinogen receptor (glycoprotein [GP] IIb/IIIa [alpha IIb/beta 3 integri n]), blocks the binding of fibrinogen to the GP IIbs/IIIa receptor, which i s 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, plac ebo-controlled, dose-ranging study in patients with recent myocardial infar ction, unstable angina, transient ischemic attack, or stroke when added to aspirin therapy. On the basis of these results, a dosing regimen was select ed for the phase III Blockage of the Glycoprotein IIb/IIIa Receptor to Avoi d Vascular Occlusion (BRAVO) trial based on pharmacodynamics and drug toler ability. In the pivotal BRAVO study, lotrafiban therapy is being evaluated in patients who have had a recent myocardial infarction, unstable angina, t ransient ischemic attack, or ischemic stroke, or who present at any time af ter a diagnosis of peripheral vascular disease combined with either cardiov ascular or cerebrovasculor disease. Results The efficacy evaluation will be based on a composite end point of c linical events (death by any cause, myocardial infarction, stroke, recurren t ischemia requiring hospitalization, or urgent ischemia-driven revasculari zation). The target enrollment is 9200 patients worldwide. Approximately 70 0 centers will participate and will be distributed within 30 countries acro ss North America, Europe, Australia, and Asia.