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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
Prabath W. B. Nanayakkara, MD;
Coen van Guldener, MD;
Piet M. ter Wee, MD, PhD;
Peter G. Scheffer, MD, PhD;
Frans J. van Ittersum, MD, PhD;
Jos W. Twisk, MD, PhD;
Tom Teerlink, MD;
Wim van Dorp, MD;
Coen D. A. Stehouwer, MD
Arch Intern Med. 2007;167(12):1262-1270.
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
Author Affiliations: Departments of Internal Medicine (Dr Nanayakkara), Nephrology (Drs ter Wee and van Ittersum), and Clinical Chemistry (Drs Scheffer and Teerlink) and Institute for Research in Extramural Medicine (Drs Twisk and Stehouwer), VU University Medical Center, Amsterdam, Department of Internal Medicine, Amphia Hospital, Breda (Dr van Guldener), Department of Nephrology, Kennemer Gasthuis, Haarlem (Dr van Dorp), and Department of Internal Medicine, University Hospital Maastricht, Maastricht (Dr Stehouwer), the Netherlands.
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