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.


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


METHODS
Ambulatory patients with stages 3 to 5 CKD.


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


METHODS
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 x 100) compared with placebo (P = 0.024), but not with gemfibrozil compared with placebo.


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


CONCLUSIONS
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.
Dogra
Gursharan
G
School of Medicine and Pharmacology, University of Western Australia and Western Australian Heart Research Institute, Perth, Western Australia. sdogra@meddent.uwa.edu.au
Irish
Ashley
A
Chan
Dick
D
Watts
Gerald
G
D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D001916:Brachial Artery / Q000503:physiopathology; D004311:Double-Blind Method; D004548:Elasticity; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D005260:Female; D015248:Gemfibrozil / Q000494:pharmacology* / Q000627:therapeutic use; D005919:Glomerular Filtration Rate; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007333:Insulin Resistance; D007676:Kidney Failure, Chronic / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D011758:Pyrroles; D000069059:Atorvastatin; D015248:Gemfibrozil