REFINING THE TREATMENT OF WOMEN WITH UNSTABLE ANGINA - A RANDOMIZED, DOUBLE-BLIND, COMPARATIVE SAFETY AND EFFICACY EVALUATION OF INTEGRELIN(TM) VERSUS ASPIRIN IN THE MANAGEMENT OF UNSTABLE ANGINA

Background: Although women typically develop coronary artery disease s everal years after men, once they have symptomatic disease their throm boembolic complications are worse than in men. The mechanism mediating this gender difference in outcome after thromboembolic events is unkn own. We previously studied platelet functions in siblings from patient s with premature coronary artery disease. We observed that platelets f rom women are more responsive than their male counterparts. In particu lar, platelets from women stimulated ex vivo with various agonists bin d more fibrinogen molecules than platelets from men. Hypothesis: We hy pothesized that in patients with acute coronary events, the control of platelet activity might require stronger antagonists in women than in men. Methods: To test this hypothesis, we investigated retrospectivel y the results of a trial on Integrelin(TM) in unstable angina. Results : We report that platelet aggregation and Holter-detected ischemic epi sodes are significantly reduced in women with unstable angina treated with the specific GPIIb-IIIa inhibitor, Integrelin, compared with the standard platelet inhibitor aspirin. In contrast, both platelet aggreg ation and Holter-detected ischemic events are well controlled in men w ith unstable angina treated with standard therapy including aspirin. C onclusion: Integrelin does provide protection in men, but, in contrast with women, not beyond what can be achieved with aspirin. Our data ar e consistent with the concept that the platelets from women require st ronger and more specific inhibitors to limit their activity, and that platelets may play a more important role in women with acute coronary syndromes than in men. Most important, specific GPIIb-IIIa inhibitors may represent a therapeutic option which provides as much suppression of ischemic events in women as they do in men with coronary artery dis ease.