Current issues in failure of antiplatelet therapy - Emerging role of catecholamines

Dr. Róbert Gábor Kiss was born in 1957. He is currently the head of Department of Cardiology at the State Health Center in Budapest and also the general secretary and board member of the Hungarian Society of Cardiology. As a specialist of internal medicine, angiology and cardiology he also holds the award of the European Cardiologist Diploma. R. G. Kiss joined the research work at the Center for Molecular and Vascular Biology at the Catholic University of Leuven, Belgium in 1992, where he earned a Ph.D. title on studying the glycoprotein IIb/IIIa receptors of platelets. As a visiting clinician at the Mayo Clinic in Minnesota, United States he was active under the leadership of Professor W. Bowie. After relocating to Hungary in 1995 he become first associate professor of medicine and then head of Departmentof Cardiology at the State Health Center. He is a distinguished member of numerous Hungarian and international societies as well as clinical groups. These include the working group on thrombosis and haemostasis of the European Society of Cardiology and the abstract grading committee of the American Heart Association. R. G. Kiss served as president of the Hungarian society of thrombosis and haemostasis between 2003 and 2005.

Abstract

Central role of platelet purinergic receptors and cyclooxygenase system in human atherothrombosis have been well-defined, and widely discussed previously. Consequently, stable coronary heart disease patients frequently require combined antiplatelet therapy for secondary prevention of recurrent atherothrombotic events. According to current guidelines, dual antiplatelet regimenis recommended after percutaneous coronary interventions with high level of evidence. However, despite uniformly applied drug doses, significantly different individual platelet inhibitory response can be detected and often referred as aspirin or clopidogrel resistance. Underlying mechanisms of antiplatelet drug resistance include reduced bioavailability of antiplatelet drugs, potential drug interactions, sustained thromboxane-A2 production (i.e. COX-2 activity of macrophages), genetic polymorphisms and finally, alternative pathways of platelet activation. Stable coronary heart disease patients with prominent in vitro adrenoceptor activity have significantly increased platelet aggregability and more functional P2Y12 receptor, indicating poor inhibitory response to thienopyridines. Therefore, platelet adrenergic receptor represents a considerable, dynamic factor of high residual platelet reactivity and might contribute to cardiovascular eventsindicating failure of antiplatelet therapy.