Differential metabolic effects of pravastatin and simvastatin in hypercholesterolemic patients

Abstract

Background: Lipophilic and hydrophilic statins have different effects on adiponectin and insulin resistance in experimental studies and different effects on the rate of onset of new diabetes in large scale clinical studies. Therefore, we hypothesized that simvastatin and pravastatin may have differential metabolic effects in hypercholesterolemic patients.

Methods: This was a randomized, single-blind, placebo-controlled, parallel study. Age, gender, and body mass index were matched. Forty-three patients were given placebo, simvastatin 20mg, or pravastatin 40 mg, respectively once daily for 2 months.

Results: Simvastatin and pravastatin therapy significantly changed lipoprotein levels and improved flow-mediated dilation after 2 months when compared with baseline (P<0.001) or placebo treatment (P<0.001 by ANOVA). Simvastatin therapy significantly increased insulin levels (mean % changes; 127%, P=0.014) and decreased plasma adiponectin levels (10%, P=0.012) and insulin sensitivity as assessed by QUICKI (6%, P=0.007) when compared with baseline. By contrast, pravastatin therapy did not significantly change insulin levels (-3%, P=0.437) but significantly increased plasma adiponectin levels (9%, P=0.011) and insulin sensitivity (6%, P=0.008) when compared with baseline. In addition, these effects of simvastatin were significant when compared with pravastatin (P<0.001 for insulin levels by ANOVA on Ranks, P<0.001 for adiponectin and P=0.001 for QUICKI by ANOVA). When compared with baseline, simvastatin significantly increased plasma leptin levels (35%, P=0.028), but pravastatin did not (1%, P=0.822).

Conclusions: Despite causing comparable changes in lipoprotein and endothelium-dependent dilation, simvastatin and pravastatin therapy had differential metabolic effects in hypercholesterolemic patients that may be clinically relevant.

Fig. 1

Simvastatin and pravastatin significantly reduced total cholesterol (mean % changes; 28 and 24%) and LDL cholesterol (40 and 35%) from baseline (both P < 0.001 by paired t-test) after 2 months administration. And these effects of simvastatin and pravastatin were also significant when compared with placebo (P < 0.001 by ANOVA). Pl, placebo; S20, simvastatin 20 mg; P40, pravastatin 40 mg. Standard error of the mean is identified by the bars.

Fig. 2

Simvastatin and pravastatin significantly improved flow-mediated dilator response to hyperemia (FMD) (mean % changes; 63 and 71%) after 2 months therapy when compared with baseline (both P < 0.001 by paired t-test). All of these effects were also significant when compared with placebo (P < 0.001 by ANOVA). Simvastatin significantly increased insulin levels (mean % changes; 127%) after 2 months therapy when compared with baseline (P = 0.014 by paired t-test). Pravastatin did not significantly change insulin levels (mean % changes; −3%) after 2 months therapy when compared with baseline (P = 0.437 by paired t-test). The effects of simvastatin to raise fasting insulin levels were significant when compared with pravastatin (P < 0.001 by ANOVA on Ranks). Pl, placebo; S20, simvastatin 20 mg; P40, pravastatin 40 mg. Standard error of the mean is identified by the bars.

Fig. 3

Simvastatin significantly decreased plasma adiponectin levels (mean % changes; 10%, P = 0.012 by paired t-test) and insulin sensitivity (mean % changes; 6%, P = 0.007 by paired t-test) when compared with baseline. Pravastatin significantly increased plasma adiponectin levels (mean % changes; 9%, P = 0.011 by paired t-test) and insulin sensitivity (mean % changes; 6%, P = 0.008 by paired t-test) when compared with baseline. Moreover, these effects of pravastatin were significant when compared with placebo and simvastatin (P < 0.001 for adiponectin and P = 0.001 for QUICKI by ANOVA). Pl, placebo; S20, simvastatin 20 mg; P40, pravastatin 40 mg. Standard error of the mean is identified by the bars.