Pravastatin: An antithrombotic effect independent of the cholesterol-lowering effect

Lipid-lowering with statins reduces blood thrombogenicity. Hour ever, it is unknown whether this is purely due to LDL-cholesterol reduction, or it is related to a statin or agent specific effect. We investigated the relations hip between reduction in blood thrombogenicity and the magnitude of low-den sity lipoprotein cholesterol (LDL-C) during pravastatin therapy. We prospectively followed for 6 months 57 hyperlipidemic patients who initi ated therapy with pravastatin, and 36 patients who were randomized into pla cebo plus diet. Pravastatin-treated patients were grouped according to the LDL-C reduction at 6 months; (i) "adequate LDL-C reduction": LDL-C reductio n >30% from baseline or LDL-C<125 mg/dl (n = 38; LDL-C reduction 74 +/- 4 m g/dl; 6-month LDL-C 119 +/- 5 mg/dl); (ii) "inadequate LDL-C reduction": ne ither of the above criteria (n = 19; LDL-C reduction 31 +/- 5 mg/dl; 6-mont h LDL-C 158 +/- 6 mg/dl). Placebo patients were divided into those " with L DL-C reduction" (n = 17, mean reduction 21 +/- 5 mg/dl) and those "without LDL reduction" (n = 19). The following parameters were altered at 6 months in both patients with "ad equate" and "inadequate" LDL-C reduction: (1) tissue plasminogen activator decreased by 1.4 +/- 0.4 and 1.5 +/- 0.5 ng/ml respectively (p = NS); (2) p lasminogen activator inhibitor-1 decreased by 8.7 +/- 2.0 and 10.1 +/- 2.7 ng/ml respectively (p = NS); (3) thrombus formation under dynamic flow cond itions decreased by 3.5 +/- 0.9 and 2.8 +/- 1.2 mu m(2) X 10(3) respectivel y (p = NS). In contrast, no significant changes from baseline were noted in placebo-treated patients, regardless of their LDL-C reduction category, an d multivariate analysis eliminated LDL-C reduction as an independent predic tor of reduction in thrombogenicity. Therefore, the reduction in thrombogenicity was not proportional to the mag nitude of LDL-C reduction suggesting that a class or agent specific propert y is primarily responsible for the pro-fibrinolytic/anti-thrombotic effects observed.