GEMFIBROZIL HAS ANTI-PLATELET EFFECTS IN PATIENTS WITH HYPERCHOLESTEROLAEMIA DURING PHYSICAL STRESS

Earlier studies indicate an increased platelet reactivity in patients with hypercholesterolaemia. Physical and mental stress have also been reported to cause increased reactivity. The present study was undertaken to evaluate the effect of gemfibrozil (G) a new lipid lowering drug on platelet reactivity during physical stress. Ten otherwise healthy male subjects with serum cholesterol levels above 7 mmol/l were involved in a double-blind study. It consisted of two treatment periods of 8 weeks during which the patients were given either G (600 mg b.i.d.) or placebo (PI) and an 8 weeks wash-out period before the cross-over. At the end of the treatment periods an exercise test was carried out and platelet reactivity tested. Adrenaline, ADP and collagen were used to induce aggregation and 5-HT and T×B₂ release measured. Plasma beta-TG and fibrinogen were also determined.

The treshold concentration of adrenaline necessary to evoke secondary aggregation was increased in 8/10 patients during exercise after G treatment and in 2/10 after PI. When the lowest ADP concentration to cause secondary aggregation (2-4 uM) was used there was a significant decrease in the 5-HT (− 44%) and T×B₂ (− 48%) secretion and a significant decrease in the area under the aggregation curve (− 28%). A decrease in 5-HT secretion was also seen after G treatment when a fixed ADP concentration of 10 uM was used. During collagen stimulation no changes were seen between the two groups. Beta-TG remained unchanged irrespective of treatment and fibrinogen showed a modest increase during exercise in both treatment groups. These results indicate a new anti-platelet effect of gemfibrozil which might be of importance in prevention of acute thrombotic events in hypercho1estero1aemic patients.