A placebo-controlled crossover study was conducted to evaluate whether
lipid-lowering with
gemfibrozil (10 to 12 weeks) affects platelet function in vivo at rest and during mental stress in 21 men with combined
hyperlipoproteinemia.
Gemfibrozil lowered plasma
triglycerides and total and
VLDL cholesterol (P < .001 for all), whereas
HDL cholesterol increased (P < .001).
Gemfibrozil increased platelet counts by 18% (P < .001) and, according to filtragometry measurements, enhanced overall (means of rest and stress values) platelet aggregability in vivo (P = .014); this effect was more evident during mental stress (P = .027) than at rest (P = .18). Moreover, the urinary excretion of 11-dehydro-thromboxane-B2 was 54% higher during treatment with
gemfibrozil (P < .001), whereas the excretion of
beta-thromboglobulin in urine was unaltered. Plasma
beta-thromboglobulin tended to be slightly elevated during active treatment (P = .15). Mental stress increased heart rate and
catecholamine levels and elevated all
cholesterol fractions (P < .01) and plasma
beta-thromboglobulin (during placebo, P = .02), but platelet aggregability did not increase significantly. A positive correlation was found between 11-dehydrothromboxane-B2 excretion and
LDL cholesterol levels during placebo (r = .62, P = .0057). In conclusion,
gemfibrozil has beneficial effects on plasma
lipoprotein levels but enhances several aspects of platelet activity in vivo and increases platelet counts. These changes might be prothrombotic and thus adverse for the hyperlipidemic patient. Primary preventive effects of
gemfibrozil might be enhanced if a
platelet inhibitor such as
aspirin is administered with
gemfibrozil.