Effect of a Treatment Strategy Consisting of Pravastatin, Vitamin E, and Homocysteine Lowering on Carotid Intima-Media Thickness, Endothelial Function, and Renal Function in Patients With Mild to Moderate Chronic Kidney Disease: Results From the Anti-Oxidant Therapy in Chronic Renal Insufficiency (ATIC) Study.
Nanayakkara, Prabath W. B. MD; van Guldener, Coen MD; ter Wee, Piet M. MD, PhD; Scheffer, Peter G. MD, PhD; van Ittersum, Frans J. MD, PhD; Twisk, Jos W. MD, PhD; Teerlink, Tom MD; van Dorp, Wim MD; Stehouwer, Coen D. A. MD
[Article]
Archives of Internal Medicine.
167(12):1262-1270, June 25, 2007.
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Background: Patients with chronic kidney disease have an increased risk of cardiovascular disease. Oxidative stress has been proposed to play a role in the development of cardiovascular disease among these patients.
Methods: We conducted a randomized, double-blind trial in 93 patients (Cockcroft-Gault equation: creatinine clearance, 38 /- 15 [mean /- SD] mL/min per 1.73 m2 [0.63 /- 0.25 mL/s per m2]) to investigate the effect of a treatment strategy designed primarily to achieve stepwise oxidative stress reduction on common carotid intima-media thickness (CC-IMT), brachial artery flow-mediated dilatation (BA-FMD), albuminuria, and renal function. The treatment group received a regimen of pravastatin to which vitamin E supplementation was added after 6 months and homocysteine-lowering therapy after another 6 months. Blood pressure in both groups was managed according to a standard protocol. The placebo group received matching placebos. Measurement of CC-IMT and BA-FMD was performed at randomization after 6, 12, and 18 months. Patients were followed up for 2 years. Generalized estimating equations were used for analysis.
Results: Compared with placebo, active treatment was associated with a decrease in CC-IMT (after 18 months: from 0.68 to 0.63 mm in the treatment group and from 0.65 to 0.71 mm in the placebo group; P<.001), an increase in BA-FMD (after 18 months: from 4.66% to 7.56% in the treatment group and from 6.21% to 4.73% in the placebo group; P<.001), and an attenuated increase in urinary albumin excretion over time (P = .04 for between-group difference after 24 months), but no effect was observed on renal function.
Conclusion: In patients with mild to moderate chronic kidney disease, 18 months of a treatment strategy along with well-controlled blood pressure reduced CC-IMT and urinary albumin excretion and increased BA-FMD.
Trial Registration: clinicaltrials.gov Identifier: NCT00384618
Copyright 2007 by the American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use. American Medical Association, 515 N. State St, Chicago, IL 60610.
