High-dose atorvastatin treatment in patients with peripheral arterial disease: Effects on platelet aggregation, blood rheology and plasma homocysteine

Abstract

Statins are used for the treatment of hypercholesterolemia. Although they are well known to have pleiotropic effects, their dose-dependent influence on platelet aggregation, hemorheologic properties and the plasma levels of homocysteine in patients with peripheral arterial disease (PAD) has not been thoroughly investigated so far. From a total of 100 patients with PAD 48 patients were randomized to a treatment with atorvastatin 80 mg/d for six months, and 52 patients served as controls who continued their medication including statins in lower doses. At baseline and at six months' follow up we assessed platelet aggregation upon stimulation with ADP, collagen and epinephrine using light transmission aggregometry. Furthermore, we determined major hemorheologic variables as well as the plasma levels of homocysteine, folic acid, and vitamin B6 and B12. No patient had obtained folic acid or B vitamin supplement. Platelet aggregation upon agonist-induced stimulation did not differ between patients under high-dose atorvastatin therapy and controls at baseline and after six months (p > 0.05). All hemorheologic parameters (plasma viscosity, red cell aggregation, whole blood viscosity, hematocrit, platelets, leucocytes) measured at baseline and after six months were not significantly different between both groups, too. After therapy with 80 mg atorvastatin homocysteine levels were significantly elevated as compared with baseline values (p = 0.0007), whereas levels remained unchanged in the control group. Folic acid levels were higher in the patients receiving high-dose atorvastatin as compared with controls both at baseline (p = 0.002) and at six months' follow up (p = 0.034). No significant difference in vitamin B6 and B12 levels both at baseline and after six months could be detected in either group. Treatment with 80 mg atorvastatin did not affect platelet aggregation and major hemorheologic parameters. The finding of an increase of homocysteine plasma levels in the presence of rather elevated levels of folic acid needs further investigation.