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

Arch Intern Med. 2007 Jun 25;167(12):1262-70. doi: 10.1001/archinte.167.12.1262.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Carotid Artery, Common / diagnostic imaging*
  • Carotid Artery, Common / physiopathology
  • Double-Blind Method
  • Drug Therapy, Combination
  • Endothelium, Vascular / physiopathology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Folic Acid / administration & dosage
  • Folic Acid / therapeutic use
  • Follow-Up Studies
  • Glomerular Filtration Rate / physiology*
  • Homocysteine / antagonists & inhibitors*
  • Homocysteine / blood
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Kidney Failure, Chronic / drug therapy*
  • Kidney Failure, Chronic / metabolism
  • Kidney Failure, Chronic / physiopathology
  • Male
  • Middle Aged
  • Oxidative Stress
  • Pravastatin / administration & dosage
  • Pravastatin / therapeutic use*
  • Pyridoxine / administration & dosage
  • Pyridoxine / therapeutic use
  • Retrospective Studies
  • Severity of Illness Index
  • Treatment Outcome
  • Ultrasonography
  • Vitamin E / administration & dosage
  • Vitamin E / therapeutic use*
  • Vitamins / administration & dosage
  • Vitamins / therapeutic use*


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Vitamins
  • Homocysteine
  • Vitamin E
  • Folic Acid
  • Pyridoxine
  • Pravastatin

Associated data

  • ClinicalTrials.gov/NCT00384618