Influences of lipid-modifying agents on hemostasis.
Drugs affecting lipid metabolism may influence, to a variable extent, the hemostatic system, that is, platelet activation, fibrinogen, and fibrinolysis. These effects may or may not be linked to the activity of these compounds on the lipid/lipoprotein profile. For this reason it may be important to consider the effects of hypolipidemic drugs on the different aspects of hemostasis, because this may allow a better understanding of their clinical use, as well as, eventually, a more proper selection in individual patients. Among the major lipid-lowering agents, fibric acids belong to a multifaceted series of abnormal fatty acids known to interact with a liver nuclear receptor, in turn activating fatty acid catabolism. A similar activity may be exerted by n-3 fatty acids from fish, as well as by other chemically related or unrelated compounds. Among fibric acids all but gemfibrozil can reduce fibrinogen levels; this last drug can, however, apparently activate fibrinolysis. Among the selective cholesterol-lowering medications, both resins and HMG CoA reductase inhibitors may reduce, in some patients, over prolonged periods of treatment, platelet sensitivity to major aggregants. This effect may be seen best with non-liver-selective agents (e.g., simvastatin), although recent data cast doubt on its constancy. A direct comparative evaluation of different HMG CoA reductase inhibitors on platelet aggregability has never been carried out. These last drugs may also reduce the circulating levels of the tissue factor pathway inhibitor (TFPI), transported by LDL in plasma, which is a potentially negative effect. A lipid-lowering molecule with antioxidant activity, for example, probucol, may also possibly play a role in controlling platelet activation.(ABSTRACT TRUNCATED AT 250 WORDS)
Sirtori
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CR
Center E. Grossi Paoletti, University of Milano, Italy.
Colli
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S
D002986:Clinical Trials as Topic; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*
D000960:Hypolipidemic Agents