NO INFLUENCE OF SIMVASTATIN TREATMENT ON PLATELET-FUNCTION IN-VIVO INPATIENTS WITH HYPERCHOLESTEROLEMIA

Hypercholesterolemia is associated with platelet activation. Reduction of plasma cholesterol levels by the 3-hydroxy-3-methylglutaryl coenzy me A reductase inhibitor simvastatin has been found to improve certain aspects of platelet function in vitro and in vivo, but controlled tri als are largely lacking. The present randomized, double-blind, crossov er study was performed to evaluate whether 10- to 12-week treatment wi th simvastatin or placebo affects platelet function in vivo in 23 hype rcholesterolemic men. Measurements were performed at rest and during m ental stress. Simvastatin treatment reduced plasma total cholesterol l evels by 18+/-12% and low density lipoprotein cholesterol levels by 26 +/-2% (P<.001 for both), whereas high density liproprotein cholesterol levels increased slightly (6+/-2%, P<.05). Platelet aggregability as assessed by filtragometry ex vivo was unaffected by simvastatin treatm ent both at rest and during mental stress. Plasma beta-thromboglobulin levels, which reflect platelet secretion, were also unaltered by simv astatin treatment both at rest (antilog of the mean: 20.2 versus 20.0 ng/mL during placebo) and during mental stress. Moreover, nocturnal ex cretion of 11-dehydrothromboxane B-2 in urine did not differ between p lacebo and active treatment: 218 versus 216 ng/mmol creatinine, respec tively. The corresponding values for urinary excretion of high-molecul ar-weight beta-thromboglobulin were 1.78 versus 1.92 ng/mmol creatinin e. Thus, simvastatin treatment had no clear-cut effect on platelet fun ction, as assessed by four different in vivo related platelet function variables, in hypercholesterolemic men.