Statins, platelet aggregation and coronary heart disease.
It is becoming increasingly recognized that the beneficial effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-Co-A) reductase inhibitors (statins) on reducing clinically important cardiovascular events (myocardial infarction and stroke) are not only attributable to their hypocholesterolemic effect but also to non-lipid mechanisms of action. The nonlipid factors may include the stabilization of arterial plaques, endothelial normalization, anti-inflammatory effects and inhibition of platelet thrombus formation. The inhibition of platelet thrombus formation has not been adequately studied in man and the results are often contradictory. It is the objective of this review to discuss the effects of statins on platelet aggregation in the context of relatively new and specific techniques for the measurement of platelet function as reported by Ma and coinvestigators in this issue of JAAMP. Ma et al. examined the effect of pravastatin given for 8 to 12 weeks on platelet function and low density lipoprotein-cholesterol (LDL-C) in 21 Chinese patients with primary hypercholesterolemia. Platelet function was evaluated by adenosine diphosphate (ADP)-induced aggregation, thromboxane B2 (TXB2) and the expression of alpha granule membrane protein-140 (GMP-140). GMP-140 is considered one of the most sensitive indicators of the state of platelet function. As expected, pravastatin treatment significantly reduced LDL-C and inhibited ADP-induced platelet aggregation, TXB2 synthesis and the expression of GMP-140--all such parameters can lead to thrombus formation and subsequent cardiovascular events. Using the test methods of Ma et al., additional dose-response studies with several statins and standard antiplatelet drugs are needed to confirm their effects on platelet aggregation, if any. Furthermore, we need to determine whether the antiplatelet effect of the statins, if present, is independent of their hypocholesterolemic action. The additional studies could provide important clues toward the development of new and specific antithrombotic drugs.
Dajani
Esam Z
EZ
International Drug Development Consultants Corp., 1549 RFD, Long Grove, IL 60047-9532, USA. EsamD@aol.com
Shahwan
Thomas G
TG
Dajani
Noura E
NE
D002318:Cardiovascular Diseases / Q000517:prevention & control*; D008078:Cholesterol, LDL / Q000187:drug effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*
D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors