Nanette K. Wenger, MD; Sandra J. Lewis, MD; David M. Herrington, MD; Vera Bittner, MD; Francine K. Welty, MD, PhD; for the Treating to New Targets Study Steering Committee and Investigators
Acknowledgments: The authors thank Andrei Breazna, Attila Kursun, David DeMicco, Liz Cusenza, Sheila Auster, and Miriam Marshood (all full-time employees of Pfizer) for their contributions in the collection and analysis of the data and John Bilbruck of Envision Pharma for editorial assistance.
Potential Financial Conflicts of Interest: Consultancies: N.K. Wenger (Eli Lilly Inc., SmithKline Beecham, DuPont Pharma, Pfizer Inc., Merck & Co. Inc., Bristol-Myers Squibb, Aventis, Sanofi-Aventis, Schering-Plough, GlaxoSmithKline, AstraZeneca, Abbott), S.J. Lewis (Pfizer Inc., Merck & Co. Inc., Bristol-Myers Squibb, AstraZeneca), D.M. Herrington (Merck & Co. Inc.), V. Bittner (Reliant Pharmaceuticals, Pfizer Inc., CV Therapeutics, Novartis), F.K. Welty (AstraZeneca); Honoraria: N.K. Wenger (Aventis, Pfizer Inc., Novartis, Merck & Co. Inc., Bristol-Myers Squibb, Eli Lilly Inc., DuPont Pharma, Searle), S.J. Lewis (Pfizer Inc., AstraZeneca, Merck & Co. Inc., Bristol-Myers Squibb), V. Bittner (Merck & Co. Inc., Merck Schering-Plough, Kos Pharmaceuticals, Pfizer Inc.), F.K. Welty (AstraZeneca, Pfizer Inc.); Grants received: N.K. Wenger (Eli Lilly Inc., AstraZeneca, Bristol-Myers Squibb, Pfizer Inc., Wyeth Ayerst, Merck & Co. Inc.), S.J. Lewis (Pfizer Inc., AstraZeneca), D.M. Herrington (Pfizer Inc.), V. Bittner (Pfizer Inc., Merck & Co. Inc., National Institutes of Health, Kos Pharmaceuticals); Grants pending: V. Bittner (Merck & Co. Inc.); Receipt of payment for manuscript preparation: V. Bittner (Pfizer Inc; attended investigator meetings at which the manuscript was discussed); Other: N.K. Wenger (data safety monitoring boards of Procter & Gamble, Knoll Pharmaceuticals, Pfizer Inc.).
Requests for Single Reprints: Nanette K. Wenger, MD, Division of Cardiology, Emory University School of Medicine, 49 Jesse Hill Jr. Drive SE, Atlanta, GA 30303; e-mail, email@example.com.
Current Author Addresses: Dr. Wenger: Division of Cardiology, Emory University School of Medicine, 49 Jesse Hill Jr. Drive SE, Atlanta, GA 30303.
Dr. Lewis: Northwest Cardiovascular Institute, 2222 North West Lovejoy Street, Suite 606, Portland, OR 97210.
Dr. Herrington: Department of Internal Medicine/Cardiology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston–Salem, NC 27157-1045.
Dr. Bittner: Division of Cardiovascular Disease, University of Alabama at Birmingham, 701 19th Street South, LHRB 310, Birmingham, AL 35294-0007.
Dr. Welty: Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215.
Author Contributions: Conception and design: N.K. Wenger, S.J. Lewis, V. Bittner.
Analysis and interpretation of the data: N.K. Wenger, S.J. Lewis, D.M. Herrington, V. Bittner, F.K. Welty.
Drafting of the article: N.K. Wenger, F.K. Welty.
Critical revision of the article for important intellectual content: N.K. Wenger, S.J. Lewis, D.M. Herrington, V. Bittner, F.K. Welty.
Final approval of the article: N.K. Wenger, S.J. Lewis, D.M. Herrington, V. Bittner, F.K. Welty.
Provision of study materials or patients: S.J. Lewis, D.M. Herrington, V. Bittner.
Collection and assembly of data: V. Bittner, F.K. Welty.
Increased life expectancy is associated with an increase in the burden of chronic cardiovascular disease.
To assess the efficacy and safety of high-dose atorvastatin in patients 65 years of age or older.
A prespecified secondary analysis of the Treating to New Targets study, a randomized, double-blind clinical trial.
256 sites in 14 countries participating in the Treating to New Targets study.
10 001 patients (3809 patients ≥65 years of age) with coronary heart disease (CHD) and low-density lipoprotein cholesterol levels less than 3.4 mmol/L (<130 mg/dL).
Patients were randomly assigned to receive atorvastatin, 10 or 80 mg/d.
The primary end point was the occurrence of a first major cardiovascular event (death from CHD, nonfatal non–procedure-related myocardial infarction, resuscitated cardiac arrest, or fatal or nonfatal stroke).
In patients 65 years of age or older, absolute risk was reduced by 2.3% and relative risk by 19% for major cardiovascular events in favor of the high-dose atorvastatin group (hazard ratio, 0.81 [95% CI, 0.67 to 0.98]; P = 0.032). Among the components of the composite outcome, the mortality rates from CHD, nonfatal non–procedure-related myocardial infarction, and fatal or nonfatal stroke (ischemic, embolic, hemorrhagic, or unknown origin) were all lower in older patients who received high-dose atorvastatin, although the difference was not statistically significant for each individual component. The improved clinical outcome in patients 65 years of age or older was not associated with persistent elevations in creatine kinase levels.
Because the study was a secondary analysis, the findings should be interpreted within the context of the main study results.
The analysis suggests that additional clinical benefit can be achieved by treating older patients with CHD more aggressively to reduce low-density lipoprotein cholesterol levels to less than 2.6 mmol/L (<100 mg/dL). The findings support the use of intensive low-density lipoprotein cholesterol-lowering therapy in high-risk older persons with established cardiovascular disease.
Wenger NK, Lewis SJ, Herrington DM, et al, for the Treating to New Targets Study Steering Committee and Investigators. Outcomes of Using High- or Low-Dose Atorvastatin in Patients 65 Years of Age or Older with Stable Coronary Heart Disease. Ann Intern Med. 2007;147:1–9. doi: 10.7326/0003-4819-147-1-200707030-00002
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Published: Ann Intern Med. 2007;147(1):1-9.
Cardiology, Coronary Risk Factors, Dyslipidemia, Geriatric Medicine.
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