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CLINICAL RESEARCH: CORONARY ARTERY DISEASE

Intensive Lipid Lowering With Atorvastatin in Patients With Coronary Heart Disease and Chronic Kidney Disease

The TNT (Treating to New Targets) Study

James Shepherd, MD^_*,_*, John J.P. Kastelein, MD, PhD, Vera Bittner, MD, FACC, Prakash Deedwania, MD, FACC, Andrei Breazna, PhD^||, Stephen Dobson, BSc^¶, Daniel J. Wilson, MD^||, Andrea Zuckerman, MD^||, Nanette K. Wenger, MD, FACC^# for the TNT (Treating to New Targets) Investigators

^_* University of Glasgow, Glasgow, United Kingdom
Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
University of Alabama at Birmingham, Birmingham, Alabama
VA Central California Healthcare System and UCSF School of Medicine, Fresno, California
^|| Pfizer Inc., New York, New York
^¶ Envision Pharma Ltd., Horsham, United Kingdom
^# Emory University School of Medicine, Atlanta, Georgia.

Manuscript received August 16, 2007; revised manuscript received November 9, 2007, accepted November 12, 2007.

^_* Reprint requests and correspondence: Dr. James Shepherd, Department of Biochemistry, Macewen Building, Glasgow Royal Infirmary, Greater Glasgow NHS, 8 Alexandra Parade, Glasgow G31 2ER, United Kingdom. (Email: jshepherd{at}gri-biochem.org.uk).

Objectives: This subanalysis of the TNT (Treating to New Targets) study investigates the effects of intensive lipid lowering with atorvastatin in patients with coronary heart disease (CHD) with and without pre-existing chronic kidney disease (CKD).

Background: Cardiovascular disease is a major cause of morbidity and mortality in patients with CKD.

Methods: A total of 10,001 patients with CHD were randomized to double-blind therapy with atorvastatin 80 mg/day or 10 mg/day. Patients with CKD were identified at baseline on the basis of an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m² using the Modification of Diet in Renal Disease equation. The primary efficacy outcome was time to first major cardiovascular event.

Results: Of 9,656 patients with complete renal data, 3,107 had CKD at baseline and demonstrated greater cardiovascular comorbidity than those with normal eGFR (n = 6,549). After a median follow-up of 5.0 years, 351 patients with CKD (11.3%) experienced a major cardiovascular event, compared with 561 patients with normal eGFR (8.6%) (hazard ratio [HR] = 1.35; 95% confidence interval [CI] 1.18 to 1.54; p < 0.0001). Compared with atorvastatin 10 mg, atorvastatin 80 mg reduced the relative risk of major cardiovascular events by 32% in patients with CKD (HR = 0.68; 95% CI 0.55 to 0.84; p = 0.0003) and 15% in patients with normal eGFR (HR = 0.85; 95% CI 0.72 to 1.00; p = 0.049). Both doses of atorvastatin were well tolerated in patients with CKD.

Conclusions: Aggressive lipid lowering with atorvastatin 80 mg was both safe and effective in reducing the excess of cardiovascular events in a high-risk population with CKD and CHD. (Treating to New Targets Study; NCT00327691 [ClinicalTrials.gov] )

Abbreviations and Acronyms   CHD = coronary heart disease   CI = confidence interval   CKD = chronic kidney disease   eGFR = estimated glomerular filtration rate   HR = hazard ratio   LDL-C = low-density lipoprotein cholesterol   MDRD = Modification of Diet in Renal Disease

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