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Received December 22, 2006
Accepted on July 29, 2007

ORIGINAL ARTICLES

Effect of Intensive Lipid Lowering with Atorvastatin on Renal Function in Patients with Coronary Heart Disease: The Treating to New Targets (TNT) Study

James Shepherd ^*1, John J.P. Kastelein , Vera Bittner , Prakash Deedwania , Andrei Breazna ^||, Stephen Dobson ^¶, Daniel J. Wilson ^**, Andrea Zuckerman ^**, Nanette K. Wenger , and Treating to New Targets Investigators

*Department of Vascular Biochemistry, University of Glasgow, Glasgow, United Kingdom; Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands; Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama; Cardiology Division, VA Central California Healthcare System and UCSF School of Medicine, Fresno, California; ||Global Research and Development and **Pfizer Global Pharmaceuticals, Pfizer Inc., New York, New York; ¶Scientific Solutions, Envision Pharma Ltd., Horsham, United Kingdom; and Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia

*Department of Vascular Biochemistry, University of Glasgow, Glasgow, United Kingdom; Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands; Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama; Cardiology Division, VA Central California Healthcare System and UCSF School of Medicine, Fresno, California; ||Global Research and Development and **Pfizer Global Pharmaceuticals, Pfizer Inc., New York, New York; ¶Scientific Solutions, Envision Pharma Ltd., Horsham, United Kingdom; and Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia

¹ To whom correspondence should be addressed. E-mail: jshepherd{at}gri-biochem.org.uk.

	Abstract

Background and objectives: Data suggest that atorvastatin may be nephroprotective. This subanalysis of the Treating to New Targets study investigated how intensive lipid lowering with 80 mg of atorvastatin affects renal function when compared with 10 mg in patients with coronary heart disease.

Design, setting, participants, & measurements: A total of 10,001 patients with coronary heart disease and LDL cholesterol levels of <130 mg/dl were randomly assigned to double-blind therapy with 10 or 80 mg/d atorvastatin. Estimated GFR using the Modification of Diet in Renal Disease equation was compared at baseline and at the end of follow-up in 9656 participants with complete renal data.

Results: Mean estimated GFR at baseline was 65.6 ± 11.4 ml/min per 1.73 m² in the 10-mg group and 65.0 ± 11.2 ml/min per 1.73 m² in the 80-mg group. At the end of follow-up (median time to final creatinine measurement 59.5 months), mean change in estimated GFR showed an increase of 3.5 ± 0.14 ml/min per 1.73 m² with 10 mg and 5.2 ± 0.14 ml/min per 1.73 m² with 80 mg (P < 0.0001 for treatment difference). In the 80-mg arm, estimated GFR improved to 60 ml/min per 1.73 m² in significantly more patients and declined to <60 ml/min per 1.73 m² in significantly fewer patients than in the 10-mg arm.

Conclusions: The expected 5-yr decline in renal function was not observed. Estimated GFR improved in both treatment groups but was significantly greater with 80 mg than with 10 mg, suggesting this benefit may be dosage related.

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