A Randomized Trial of the Effect of Statin and Fibrate Therapy on Arterial Function in CKD

Background

Although patients with chronic kidney disease (CKD) are at increased risk of cardiovascular disease (CVD), the roles of lipid-modifying therapies in decreasing CVD risk are unclear. Our aim is to compare the effects of statin and fibrate therapy on arterial function as a risk marker of CVD.

Study Design

Double-blind, randomized, placebo-controlled, parallel-group study.

Setting & Participants

Ambulatory patients with stages 3 to 5 CKD.

Intervention

6 weeks of atorvastatin, 40 mg/d, or gemfibrozil, 600 mg twice daily, with placebo.

Outcomes & Measurements

Primary outcome was arterial function assessed by means of endothelial-dependent flow-mediated dilatation (FMD) and small-artery compliance (C2). Secondary outcomes included endothelial-independent glyceryl trinitrate–mediated dilatation (GTNMD), large-artery compliance (C1), and levels of lipids, lipoproteins, and oxidized low-density lipoprotein, as well as markers of insulin resistance and inflammation.

Results

Compared with placebo, atorvastatin significantly decreased low-density lipoprotein (−52%), triglyceride (−30%), and oxidized low-density lipoprotein levels (−41%; P < 0.0001). Gemfibrozil significantly decreased triglyceride levels (−40%) and increased high-density lipoprotein levels (+20%; P < 0.0001). Neither atorvastatin nor gemfibrozil had a significant effect on markers of insulin resistance or inflammation. There was no significant change in FMD, GTNMD, or C1 with either atorvastatin or gemfibrozil. There was improvement in C2 with atorvastatin (+1.1 mL/mm Hg × 100) compared with placebo (P = 0.024), but not with gemfibrozil compared with placebo.

Limitations

Small sample size leading to inadequate power, short duration of therapy, and use of a heterogeneous group of patients with CKD and dialysis patients.

Conclusion

In patients with advanced CKD, atorvastatin is associated with improvement in dyslipidemia and small-artery stiffness, but not endothelial function. Gemfibrozil improves dyslipidemia, but has no effect on arterial function.

Index Words: Chronic kidney disease, endothelial function, arterial compliance, dyslipidemia, statin, fibrate