Antiplatelet and anticoagulant drugs in coronary vascular disease.
The stimulation of platelets, activation of the coagulation cascade, release of platelet-derived vasoconstrictors, and endothelial dysfunction all contribute to the thrombotic vascular occlusion that results in myocardial infarction. Despite the importance of platelets in the initiation of this process, they are activated by multiple endogenous mediators. Thus, one might anticipate that redundancy in the system would confound the efficacy of antiplatelet drugs that were mediator-specific. The success of aspirin in clinical trials is likely to reflect the role of thromboxane A2 (TxA2) as an amplification signal for other platelet agonists. Activated platelets provide a substrate for assembly of the prothrombinase complex and both heparin and warfarin also reduce the mortality due to thrombotic vascular disease. The relative efficacy of these compounds versus aspirin and the safety of their combination, particularly in the setting of therapeutic thrombolysis, are under investigation. Novel antiplatelet agents, particularly those directed against the glycoprotein 11b/111a complex, are more potent than aspirin in animal models. Similarly, direct thrombin inhibitors seem superior to heparin. Whether such compounds can be administered safely in effective doses to humans is under study. It is hoped that the success of aspirin does not impede the clinical evaluation of theoretically more attractive antithrombotic drugs.
FitzGerald
G A
GA
Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN.
Shipp
E
E
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects; D003328:Coronary Thrombosis / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D013928:Thromboxane A2 / Q000502:physiology
D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D013928:Thromboxane A2; D001241:Aspirin