Beyond heparin and aspirin: new treatments for unstable angina and non-Q-wave myocardial infarction.
The goals of therapy for unstable angina and non-Q-wave myocardial infarction (MI) are to maintain myocardial perfusion by inhibiting platelet aggregation and fibrin deposition at sites of plaque rupture, thereby preventing ongoing or new myocardial ischemia and cardiac death. Although aspirin and heparin sodium are cornerstones in the management of unstable angina and non-Q-wave MI, both have significant limitations that have prompted the development of new agents. The thienopyridines, ticlopidine hydrochloride and clopidogrel, appear to be at least as effective as aspirin in the management of unstable angina. Glycoprotein IIb/IIIa receptor antagonists are a new class of platelet inhibitors that are more potent than aspirin, because they target the final common pathway of platelet aggregation. Low-molecular-weight heparins provide a more stable pharmacodynamic response and are more convenient to use than unfractionated heparin. Direct thrombin inhibitors show promise for inhibiting thrombin-mediated platelet aggregation and fibrin deposition. We focus on the opportunities presented by these agents, detailing mechanisms of action, advantages over aspirin and heparin, and performance in recent clinical trials.
Weitz
J I
JI
Department of Medicine, McMaster University, Hamilton Civic Hospital Research Center, Ontario, Canada. jweitz@thrombosis.hhscr.org
Bates
S M
SM
D000789:Angina, Unstable / Q000188:drug therapy*; D000991:Antithrombins / Q000627:therapeutic use*; D000077144:Clopidogrel; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D024764:Hirudin Therapy; D006629:Hirudins / Q000031:analogs & derivatives; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology*; D010446:Peptide Fragments / Q000627:therapeutic use; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000627:therapeutic use; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use
D000991:Antithrombins; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D006629:Hirudins; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D017482:Receptors, Thromboxane; D011994:Recombinant Proteins; D000077144:Clopidogrel; D013930:Thromboxane-A Synthase; D013988:Ticlopidine; C074619:bivalirudin