The DOI matches its Crossref record; 25 of the 27 references it cites were found in a registry or an index.
Effect of Lowering LDL Cholesterol Substantially Below Currently Recommended Levels in Patients With Coronary Heart Disease and Diabetes
Open accessAbstract
OBJECTIVE—The Treating to New Targets study showed that intensive lipid-lowering therapy with atorvastatin 80 mg/day provides significant clinical benefit beyond that afforded by atorvastatin 10 mg/day in patients with stable coronary heart disease (CHD). The objective of our study was to investigate whether similar benefits of high-dose intensive atorvastatin therapy can be achieved in patients with CHD and diabetes. RESEARCH DESIGN AND METHODS—A total of 1,501 patients with diabetes and CHD, with LDL cholesterol levels of <130 mg/dl, were randomized to double-blind therapy with either atorvastatin 10 (n = 753) or 80 (n = 748) mg/day. Patients were followed for a median of 4.9 years. The primary end point was the time to first major cardiovascular event, defined as death from CHD, nonfatal non–procedure-related myocardial infarction, resuscitated cardiac arrest, or fatal or nonfatal stroke. RESULTS—End-of-treatment mean LDL cholesterol levels were 98.6 mg/dl with atorvastatin 10 mg and 77.0 mg/dl with atorvastatin 80 mg. A primary event occurred in 135 patients (17.9%) receiving atorvastatin 10 mg, compared with 103 patients (13.8%) receiving atorvastatin 80 mg (hazard ratio 0.75 [95% CI 0.58–0.97], P = 0.026). Significant differences between the groups in favor of atorvastatin 80 mg were also observed for time to cerebrovascular event (0.69 [0.48–0.98], P = 0.037) and any cardiovascular event (0.85 [0.73–1.00], P = 0.044). There were no significant differences between the treatment groups in the rates of treatment-related adverse events and persistent elevations in liver enzymes. CONCLUSIONS—Among patients with clinically evident CHD and diabetes, intensive therapy with atorvastatin 80 mg significantly reduced the rate of major cardiovascular events by 25% compared with atorvastatin 10 mg.
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“Subgroup analyses of people with diabetes in larger trials (101-105) and trials in people with diabetes (106,107) showed significant primary and secondary prevention of ASCVD events and CHD death in people with diabetes.”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [104]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“Subgroup analyses of people with diabetes in larger trials (94–98) and trials in people with diabetes (99,100) showed significant primary and secondary prevention of ASCVD events and coronary heart disease (CHD) death in people with diabetes.”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [97]
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In the citing paper
“Although statins are efficacious in patients with type 2 diabetes, rates of cardiovascular events remain elevated in such patients even after statin treatment.7–9”
From Effects of Combination Lipid Therapy in Type 2 Diabetes Mellitus (2010) · cites this paper as [8]
In the citing paper
“Lipid profile has long been considered among the most important risk factors for CVD in T2DM, and several trials have confirmed that lowering low-density lipoprotein cholesterol (LDL-C) via statins in T2DM was effective in reducing the risk of CVD [81, 82].”
From Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007–2017 (2018) · cites this paper as [82]
In the citing paper
“A subgroup analysis of 1501 diabetic patients included in the Treating to New Targets (TNT) study, which compared intensive statin therapy (atorvastatin 80 mg) with standard statin therapy (atorvastatin 10 mg), showed a reduction in risk of primary events, cerebrovascular events, and all cardiovascular events in patients in the intensive statin therapy group.442”
From European Guidelines on cardiovascular disease prevention in clinical practice (version 2012) (2012) · cites this paper as [442]
In the citing paper
“These recommendations are based on the observation that high-intensity versus moderate-intensity statin therapy reduces cardiovascular event rates in high-risk individuals with established cardiovascular disease in randomized trials (95,107).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [95]
In the citing paper
“Subgroup analyses of people with diabetes in larger trials (92 -96) and trials in people with diabetes (97,98) showed signi fi cant primary and secondary prevention of ASCVD events and CHD death in people with diabetes.”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [95]
In the citing paper
“For patients with a myocardial infarction history, it has been reported that the risk of recurrence of cardiovascular events increases with the presence of diabetes137, 749–751).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [751]
In the citing paper
“According to a meta-analysis by the Cholesterol Treatment Trialists' (CTT) Collaboration, the effects of LDL-C-lowering therapy using statins on cardiovascular event are equal regardless of whether the patient had diabetes751).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [751]
In the citing paper
“These effects were similar to those in nondiabetic subjects751).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [751]
In the citing paper
“Subanalyses of diabetic subgroups of larger trials (186–190) and trials specifically in subjects with diabetes (191,192) showed significant primary and secondary prevention of CVD events ± CHD deaths in diabetic populations.”
From Standards of Medical Care in Diabetes—2009 (2009) · cites this paper as [189]
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European Guidelines on cardiovascular disease prevention in clinical practice (version 2012)
Authors/Task Force Members:, Perk, J., De Backer, G., Gohlke, H., Graham, I., Reiner, Ž., Verschuren, M., Albus, C., Benlian, P., Boysen, G., et al. (2012) · European Heart Journal · doi:10.1093/eurheartj/ehs092 · Cited by 8,490
2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes
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2016 European Guidelines on cardiovascular disease prevention in clinical practice
Piepoli, M. F., Hoes, A. W., Agewall, S., Albus, C., Brotons, C., Catapano, A. L., Cooney, M.-T., Corrà, U., Cosyns, B., Deaton, C., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw106 · Cited by 6,457
Standards of medical care in diabetes—2014
American Diabetes Association (2014) · Diabetes Care · doi:10.2337/dc14-s014 · Cited by 4,572
Metadata
- Authors
- Shepherd, J., Barter, P., Carmena, R., Deedwania, P., Fruchart, J.-C., Haffner, S., Hsia, J., Breazna, A., LaRosa, J., Grundy, S., Waters, D., & for the Treating to New Targets Investigators
- Affiliations
- University of Glasgow (GB)
- The University of Sydney (AU)
- Universitat de València (ES)
- University of California, San Francisco (US)
- Inserm (FR)
- The University of Texas at San Antonio Health Science Center (US)
- George Washington University Hospital (US)
- Pfizer (United States) (US)
- SUNY Downstate Health Sciences University (US)
- The University of Texas Southwestern Medical Center (US)
- San Francisco General Hospital (US)
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2006-06-01
- Volume
- 29
- Issue
- 6
- Pages
- 1220-1226
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2160390128
- Cited by
- 525
- References
- 27
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 13 · 2023: 16 · 2022: 10 · 2021: 10 · 2020: 18 · 2019: 21 · 2018: 26 · 2017: 16 · 2016: 25 · 2015: 25 · 2014: 33 · 2013: 35 · 2012: 37
- FWCI
- 47.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Coronary Interventions and Diagnostics
- Keywords
- atorvastatin, intensive lipid-lowering therapy, LDL cholesterol lowering, coronary artery disease, diabetes mellitus, major adverse cardiovascular events, cardiovascular risk reduction, statin dose comparison
- MeSH terms
- Atorvastatin, Aged, Blood Pressure, Coronary Disease, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Dose-Response Relationship, Drug, Female, Heptanoic Acids, Humans, Cholesterol, HDL, Cholesterol, LDL, Male, Middle Aged, Pyrroles, Triglycerides, Hydroxymethylglutaryl-CoA Reductase Inhibitors
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