Differential metabolic effects of rosuvastatin and pravastatin in hypercholesterolemic patients

Abstract

Background: Rosuvastatin and pravastatin have differential hydrophilicity and potency to inhibit hydroxymethylglutaryl-CoA reductase that may be relevant to changes in adiponectin levels, insulin resistance, and the rate of new onset diabetes in large clinical studies. Therefore, we hypothesized that rosuvastatin 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. Fifty-four patients were given placebo, rosuvastatin 10mg, or pravastatin 40mg, respectively once daily for 2 months.

Results: When compared with pravastatin therapy, rosuvastatin therapy significantly reduced total, LDL cholesterol, and apolipoprotein B levels (P<0.05 by post-hoc comparison), but comparably improved flow-mediated dilation after 2 months. Interestingly, rosuvastatin therapy significantly increased fasting insulin (mean % changes; 28%, P=0.005). and HbA1c (1%, P=0.038) while decreasing plasma adiponectin levels (9%, P=0.010) and insulin sensitivity (assessed by QUICKI; 2%, P=0.007) when compared with baseline. By contrast, pravastatin therapy significantly decreased fasting insulin (8%, P=0.042), and HbA1c levels (1%, P=0.019) while increasing plasma adiponectin levels (36%, P=0.006) and insulin sensitivity (3%, P=0.005) when compared with baseline. Moreover, these differential effects were evident when outcomes of rosuvastatin and pravastatin therapy were directly compared (P=0.002 for insulin levels by ANOVA on Ranks, P=0.003 for adiponectin, P=0.003 for QUICKI, and P=0.010 for HbA1c by ANOVA).

Conclusions: While significantly reducing lipoprotein profiles, rosuvastatin therapy had unwanted metabolic effects in hypercholesterolemic patients when compared with pravastatin therapy, that may be clinically relevant in patients prone to metabolic diseases.