Glycoprotein IIb/IIIa antagonism and fibrinolytic therapy for acute myocardial infarction.
Fibrinolytic therapy for the treatment of ST-segment elevation myocardial infarction unquestionably reduces mortality when administered within 12 hours of symptom onset. By promptly restoring antegrade perfusion, infarct size is limited, ventricular function is less compromised, and mortality rates are lowered. Although fibrinolytic therapy initially restores antegrade flow in the infarct vessel in the majority of patients, sustained, tissue-level reperfusion occurs in only approximately one fourth of patients. Thrombin and platelets associated with a coronary thrombus are not specifically targeted by fibrinolytic agents, but rather have paradoxically increased activity. These components contribute to the tendency for vessel reocclusion after initially successful reperfusion. Thus, adjunctive therapy with antithrombins and antiplatelet agents are essential in the successful treatment of a coronary thrombus. Although aspirin has been shown to reduce mortality in acute myocardial infarction, it is a weak antiplatelet agent that is pathway specific. Glycoprotein IIb/IIIa inhibitors are potent antiplatelet agents that block the final common pathway for platelet aggregation. Thus, the growing evidence of platelet preeminence in the pathophysiology of failed thrombolysis has lead to the study of combination drug therapy with glycoprotein IIb/IIIa inhibition and reduced dose fibrinolytic agents in the treatment of acute ST-segment elevation myocardial infarction. This article reviews the rationale, results, and clinical implications of the major trials of combination drug therapy in acute myocardial infarction.
Vivekananthan
Deepak P
DP
Dept. of Cardiovascular Medicine, F-25, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195, USA.
Patel
Vasant B
VB
Moliterno
David J
DJ
D000818:Animals; D002986:Clinical Trials as Topic; D003328:Coronary Thrombosis / Q000503:physiopathology / Q000517:prevention & control; D004353:Drug Evaluation, Preclinical; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D015912:Thrombolytic Therapy
D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex