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J Am Coll Cardiol, 2008; 51:1448-1454, doi:10.1016/j.jacc.2007.11.072
© 2008 by the American College of Cardiology Foundation
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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{dagger}, Vera Bittner, MD, FACC{ddagger}, 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
{dagger} Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
{ddagger} 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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