A Randomized Trial of the Effect of Statin and Fibrate Therapy on Arterial Function in CKD
Received 23 October 2006; accepted 6 March 2007. published online 26 April 2007.
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.
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.
1School of Medicine and Pharmacology, University of Western Australia and Western Australian Heart Research Institute, Perth, Western Australia
2Department of Nephrology, Royal Perth Hospital, Perth, Western Australia.
Address correspondence to Gursharan Dogra, MBBCh, FRACP, PhD, School of Medicine and Pharmacology, Level 4, MRF Bldg, Royal Perth Hospital, Box X2213 GPO Perth, Western Australia 6847.
Support: This study was supported by Medical Research Grants from Pfizer Cardiovascular Lipid (CVL) grants, the Faculty of Medicine and Dentistry at the University of Western Australia, and the Royal Perth Hospital Medical Research Foundation. Potential conflicts of interest: None.
ABSTRACT