Current issues in thrombosis prevention with antiplatelet drugs.
In this review, the major current problems related to the pharmacology and clinical use of antiplatelet drugs are discussed in relation to the physiopathology of the platelet-vessel wall interaction and arterial thrombus formation. Although platelet adhesion to injured vessels is a crucial step in thrombogenesis, none of the currently used antiaggregating drugs prevents this phenomenon. Why the normal endothelium does not react with platelets is not known. Thus we are unable to pharmacologically restore endothelial 'non-thrombogenicity' when lost by single or repeated injury. In contrast, more information is available on the mechanisms controlling and amplifying platelet activation by physiological stimuli (such as collagen and thrombin), and on their pharmacological modulation. The 3 main amplification loops involve arachidonic acid metabolism, ADP release and possibly the availability of a phospholipid platelet activating factor. These pathways are in turn activated by the phosphatidylinositol cycle. The most widely used antiaggregating drug is aspirin. It prevents the formation of arachidonic acid metabolites both in platelets and in vascular cells. The use of low-dose aspirin, thromboxane-synthase inhibitors, thromboxane receptor antagonists, epoprostenol (prostacyclin) and its stable analogues, and ticlopidine all appear to be promising pharmacological approaches, but none has so far been tested in clinical trials for thrombosis prevention. On the other hand, aspirin (in relatively large doses of 300 to 1500 mg daily), sulphinpyrazone and dipyridamole have been tested alone or in combination in the secondary prevention of thromboembolic complications. Aspirin has significantly reduced both the occurrence of myocardial infarction and mortality rate in patients with unstable angina and/or previous myocardial infarction; it has also proved beneficial in cerebrovascular disease. The beneficial effect of aspirin was dose-independent. In some of these trials aspirin was combined with either dipyridamole or sulphinpyrazone. When used alone, the latter compound has reduced sudden death or thromboembolic complications in patients with myocardial infarction. It remains to be established whether antiplatelet therapy may prevent or stop the progression of atherosclerosis.
D001241:Aspirin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D001026:Coronary Artery Bypass; D003327:Coronary Disease / Q000188:drug therapy; D004727:Endothelium / Q000502:physiology; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use; D005337:Fibrin / Q000096:biosynthesis; D005342:Fibrinolysis; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D011982:Receptors, Prostaglandin / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D013927:Thrombosis / Q000097:blood / Q000517:prevention & control*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D005343:Fibrinolytic Agents; D011982:Receptors, Prostaglandin; D005337:Fibrin; D011464:Epoprostenol; D013930:Thromboxane-A Synthase; D001241:Aspirin