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CLINICAL RESEARCH: LIPIDS POST-CORONARY BYPASS

Intensive Lipid-Lowering With Atorvastatin for Secondary Prevention in Patients After Coronary Artery Bypass Surgery

Sanjiv J. Shah, MD^_*,, David D. Waters, MD^_*,_*, Philip Barter, MD, John J.P. Kastelein, MD, PhD, James Shepherd, MD^||, Nanette K. Wenger, MD^¶, David A. DeMicco, DPharm^#, Andrei Breazna, PhD^# and John C. LaRosa, MD^_**

^_* Division of Cardiology, San Francisco General Hospital, and the Department of Medicine, University of California, San Francisco, California
Division of Cardiology, Department of Medicine, Northwestern University, Chicago, Illinois
Heart Research Institute, Sydney, Australia
Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
^|| University of Glasgow, Glasgow, United Kingdom
^¶ Emory University School of Medicine, Atlanta, Georgia
^# Pfizer Inc., New York, New York
^_** State University of New York Health Science Center, New York, New York.

Manuscript received October 12, 2007; revised manuscript received December 12, 2007, accepted December 17, 2007.

^_* Reprint requests and correspondence to: Dr. David D. Waters, Room 5G1, Division of Cardiology, San Francisco General Hospital, 1001 Potrero Avenue, San Francisco, California 94110. (Email: dwaters{at}medsfgh.ucsf.edu).

Objectives: The aim of this post hoc analysis from the TNT (Treating to New Targets) trial is to determine whether patients with previous coronary artery bypass grafting (CABG) surgery achieved clinical benefit from intensive low-density lipoprotein (LDL)-cholesterol lowering.

Background: The development and progression of atherosclerosis is accelerated in coronary venous bypass grafts.

Methods: A total of 10,001 patients with documented coronary disease, including 4,654 with previous CABG, were randomized to atorvastatin 80 or 10 mg/day and were followed for a median of 4.9 years. The primary end point was the occurrence of a first major cardiovascular event (cardiac death, nonfatal myocardial infarction, resuscitated cardiac arrest, or stroke).

Results: A first major cardiovascular event occurred in 11.4% of the patients with prior CABG and 8.5% of those without prior CABG (p < 0.001). In CABG patients, mean LDL-cholesterol levels at study end were 79 mg/dl in the 80-mg arm and 101 mg/dl in the 10-mg arm, and the primary event rate was 9.7% in the 80-mg arm and 13.0% in the 10-mg arm (hazard ratio 0.73, 95% confidence interval 0.62 to 0.87, p = 0.0004). Repeat revascularization during follow-up, either CABG or percutaneous coronary intervention, was performed in 11.3% of the CABG patients in the 80-mg arm and 15.9% in the 10-mg arm (hazard ratio 0.70, 95% confidence interval 0.60 to 0.82, p < 0.0001).

Conclusions: Intensive LDL-cholesterol lowering to a mean of 79 mg/dl with atorvastatin 80 mg/day in patients with previous CABG reduces major cardiovascular events by 27% and the need for repeat coronary revascularization by 30%, compared with less intensive cholesterol-lowering to a mean of 101 mg/dl with atorvastatin 10 mg/day. (A Study to Determine the Degree of Additional Reduction in CV Risk in Lowering LDL Below Minimum Target Levels [TNT]; NCT00327691 [ClinicalTrials.gov] )

Abbreviations and Acronyms   CABG = coronary artery bypass graft surgery   CHD = coronary heart disease   CI = confidence interval   HR = hazard ratio   LDL = low-density lipoprotein   SVG = saphenous vein graft

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