Coronary artery diseaseSafety and Efficacy of Atorvastatin-Induced Very Low-Density Lipoprotein Cholesterol Levels in Patients With Coronary Heart Disease (a Post Hoc Analysis of the Treating to New Targets [TNT] Study)†
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Study design and patients
The study protocol and outcome measures for the TNT trial have been published previously.1, 2 All patients gave written informed consent, and the study was approved by the local research ethics committee or institutional review board at each center. In brief, patients with clinically evident CHD (defined as previous myocardial infarction [MI] or previous or present angina with objective evidence of atherosclerotic CHD and/or those who had undergone coronary revascularization procedures)
Patient population
In the TNT study, 10,001 patients were randomized and given double-blind treatment with atorvastatin 10 or 80 mg. Of these, 9,769 (97.7%) had LDL cholesterol measurements taken after 3 months, and this group was stratified into quintiles (Table 1).
Baseline characteristics across quintiles are listed in Table 2. Patients in the quintile with the lowest levels of on-treatment LDL cholesterol concentrations were slightly more likely to be older, to be men, to have lower systolic and diastolic
Discussion
The present analysis supports the quantitative relation between reduced LDL cholesterol and reduced CHD risk and demonstrates that this association exists even at very low LDL cholesterol levels. In the TNT cohort, there was a consistent and highly significant reduction in the rate of major cardiovascular events with decreasing levels of on-treatment LDL cholesterol, with the lowest event rate observed in patients with LDL cholesterol <64 mg/dl (1.7 mmol/L). The incremental clinical benefit at
Acknowledgment
A full list of TNT investigators has been published previously.1 We acknowledge the contributions made by Andrei Breazna, Liz Cusenza, Sheila Auster, and Miriam Marshood, all employees of Pfizer, in the collection and analysis of the data and John Bilbruck of Envision Pharma, Inc., Horsham, United Kingdom (a medical writer funded by Pfizer), for editorial assistance.
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The Treating to New Targets study was funded by Pfizer, Inc., New York, New York.
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Conflicts of interest: Dr. LaRosa has served as a consultant to Pfizer, Inc., New York, New York; Merck Whitehouse Station, New Jersey; Bristol-Myers Squibb, New York, New York; and AstraZeneca, Wilmington, Delaware; and has received lecture fees from Pfizer. Dr. Grundy has consulted with Abbott, Chicago, Illinois; GlaxoSmithKline, Durham, North Carolina, Pfizer, AstraZeneca, and Sanofi-Aventis, Bridgewater, New Jersey; received lecture fees from Merck Schering Plough, Kenilworth, New Jersey; Kos, Edison, New Jersey, Pfizer, GlaxoSmithKline, Lilly, and Bristol-Myers Squibb; and received research support from Abbott and GlaxoSmithKline. Dr. Kastelein has received consulting fees, lecture fees, and grant support from Pfizer, Merck Schering Plough, Bristol-Myers Squibb, and Sankyo, Munich, Germany; Dr. Kostis has served as a consultant to Pfizer, Schering Plough, Berlex, Montville, New Jersey; Taisho, Tokyo, Japan; Forest Laboratories, New York, New York; and Sankyo; received lecture fees from Pfizer, Merck, Bristol-Myers Squibb, AstraZeneca, Sanofi Aventis, and Otsuka, Rockville, Maryland; and received grant support from Pfizer and Schering Plough. Dr. Greten has received consulting and lecturing fees from Pfizer, Merck, Schering Plough, and Kowa Company, Nagoya, Japan.