Simvastatin Effects in Normo‐ and Hypercholesterolaemic Patients with Peripheral Arterial Occlusive Disease: A Pilot Study

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Abstract
Improvement of endothelial function caused by statin treatment is not related to lowering of the cholesterol levels but results primarily from statin pleiotropic effects. Accordingly, we designed a pilot study in 10 normocholesterolaemic and 10 hypercholesterolaemic patients with peripheral arterial occlusive disease to investigate potential biological effects of statins in relation to their effects on endothelial function. The patients were treated with simvastatin 40 mg/daily for 3 months. Simvastatin led to significant reduction in total cholesterol and trigliceride levels in normocholesterolaemic and hypercholesterolaemic patients. Elongation of pain‐free and total walking distance was observed in both groups studied. Inconsiderable changes in rest ankle brachial index were seen. Flow‐mediated dilation increased in normocholesterolaemic group by 153% and in the hypercholesterolaemic group by 180% after 3 months of treatment. Euglobulin clot lysis time was shortened significantly in both groups each time after drug intake. Platelet aggregates ratio was increased in normocholesterolaemic patients by 8.9% and in hypercholesterolaemic patients by 17.6% each time after intake and remained significantly increased during the observation after 1 and 3 months. Simvastatin inhibited platelet aggregation induced by collagen and ADP in both study groups 3 hr after intake, but the platelets of hypercholesterolaemic patients were less sensitive to these aggregatory agents after 3 months of treatment. Simvastatin therapy caused clinical improvement in normocholesterolaemic and hypercholesterolaemic patients with peripheral occlusive disease. It is suggested that this effect is due to the restoration of endothelial function.