Author + information
- Received October 12, 2007
- Revision received December 12, 2007
- Accepted December 17, 2007
- Published online May 20, 2008.
- 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⁎⁎
- ↵⁎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.
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)
Funding for the study was provided by Pfizer Inc. Dr. Waters has received investigator-initiated research funding from Merck; consulting fees from Merck, Schering-Plough, and Pfizer; and honoraria for lectures from Pfizer. Dr. Barter has received grant support from Pfizer; consulting fees from AstraZeneca, LifeCycle Pharma, Merck, and Sanofi-Aventis; and honoraria for lectures from AstraZeneca, Fournier-Pharma, Merck, Pfizer, and Sanofi-Aventis. Dr. Kastelein has received grant support, consulting fees, and honoraria for lectures from AstraZeneca, Bristol-Myers Squibb, Merck, Pfizer, Sankyo, and Schering-Plough. Dr. Shepherd has received consulting fees from AstraZeneca, GlaxoSmithKline, Merck, Schering-Plough, and Oxford Biosensors and honoraria for lectures from AstraZeneca, Merck, Pfizer, and Schering-Plough. Dr. Wenger has received grant support from Merck and Pfizer, and consulting fees from Abbott, AstraZeneca, CV Therapeutics, Merck, Pfizer, Schering-Plough, and Sanofi-Aventis. Dr. DeMicco is a Pfizer employee. Dr. Breazna is a Pfizer employee. Dr. LaRosa has received consulting fees from AstraZeneca, Bristol-Myers Squibb, Merck, and Pfizer, and honoraria for lectures from Pfizer.
- Received October 12, 2007.
- Revision received December 12, 2007.
- Accepted December 17, 2007.
- American College of Cardiology Foundation