Therapeutic approaches in arterial thrombosis.
The current standard of care for the treatment of arterial thrombosis includes anticoagulants and three classes of antiplatelet agents--aspirin, thienopyridines and glycoprotein IIb-IIIa antagonists. Although these drugs have had a significant impact on morbidity and mortality in several patient populations, up to 15% of the high risk patients with acute coronary syndrome continue to suffer from ischemic events. This problem may occur, in part, because the platelets in many patients are non-responsive to aspirin and clopidogrel. Murine models now indicate that platelets are not only responsible for arterial occlusion, they are also involved in the progression of atherosclerotic disease. New opportunities have emerged identifying potential targets and strategies for drug discovery suited to address these deficiencies by more effectively modulating platelet adhesion, thrombus growth, thrombus stability and the pro-inflammatory activity of platelets. In addition, a growing need has emerged for the development of bedside devices capable of bringing personalized medicine to patients being treated with antithrombotic drugs in order to measure the pharmacodynamic activities of new therapies, to assess the activities achieved by combined antithrombotic therapy, and to identify patients that fail to respond.
Phillips
D R
DR
Portola Pharmaceuticals, Inc., San Francisco, CA 94402, USA. dphillips@portola.com
Conley
P B
PB
Sinha
U
U
Andre
P
P
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000925:Anticoagulants / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use; D050197:Atherosclerosis / Q000188:drug therapy*; D001792:Blood Platelets / Q000166:cytology* / Q000187:drug effects; D000077144:Clopidogrel; D003328:Coronary Thrombosis / Q000188:drug therapy*; D004195:Disease Models, Animal; D018450:Disease Progression; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D008954:Models, Biological; D010973:Platelet Adhesiveness / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000627:therapeutic use; D012306:Risk; D015398:Signal Transduction; D013927:Thrombosis; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011725:Pyridines; C446540:thienopyridine; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin