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Implications of Recent Clinical Trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines
Open accessAbstract
The Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program issued an evidence-based set of guidelines on cholesterol management in 2001. Since the publication of ATP III, 5 major clinical trials of statin therapy with clinical end points have been published. These trials addressed issues that were not examined in previous clinical trials of cholesterol-lowering therapy. The present document reviews the results of these recent trials and assesses their implications for cholesterol management. Therapeutic lifestyle changes (TLC) remain an essential modality in clinical management. The trials confirm the benefit of cholesterol-lowering therapy in high-risk patients and support the ATP III treatment goal of low-density lipoprotein cholesterol (LDL-C) <100 mg/dL. They support the inclusion of patients with diabetes in the high-risk category and confirm the benefits of LDL-lowering therapy in these patients. They further confirm that older persons benefit from therapeutic lowering of LDL-C. The major recommendations for modifications to footnote the ATP III treatment algorithm are the following. In high-risk persons, the recommended LDL-C goal is <100 mg/dL, but when risk is very high, an LDL-C goal of <70 mg/dL is a therapeutic option, ie, a reasonable clinical strategy, on the basis of available clinical trial evidence. This therapeutic option extends also to patients at very high risk who have a baseline LDL-C <100 mg/dL. Moreover, when a high-risk patient has high triglycerides or low high-density lipoprotein cholesterol (HDL-C), consideration can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug. For moderately high-risk persons (2+ risk factors and 10-year risk 10% to 20%), the recommended LDL-C goal is <130 mg/dL, but an LDL-C goal <100 mg/dL is a therapeutic option on the basis of recent trial evidence. The latter option extends also to moderately high-risk persons with a baseline LDL-C of 100 to 129 mg/dL. When LDL-lowering drug therapy is employed in high-risk or moderately high-risk persons, it is advised that intensity of therapy be sufficient to achieve at least a 30% to 40% reduction in LDL-C levels. Moreover, any person at high risk or moderately high risk who has lifestyle-related risk factors (eg, obesity, physical inactivity, elevated triglycerides, low HDL-C, or metabolic syndrome) is a candidate for TLC to modify these risk factors regardless of LDL-C level. Finally, for people in lower-risk categories, recent clinical trials do not modify the goals and cutpoints of therapy.
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“The use of combination fibrate–statin therapy in such patients is consistent with current guidelines that recommend treatment for patients with hypertriglyceridemia and low HDL cholesterol levels that persist despite statin therapy.25”
From Effects of Combination Lipid Therapy in Type 2 Diabetes Mellitus (2010) · cites this paper as [25]
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In the citing paper
“According to practice guidelines in place at the time of patient enrollment in IMPROVE-IT, treatment of hypercholesterolemia was based on lowering LDL cholesterol to target levels, 20,21 which were set on the basis of a patient's risk of cardiovascular events.”
From Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes (2015) · cites this paper as [20]
In the citing paper
“Statins are currently the most effective agents available for managing dyslipidemia and have been shown to reduce CV events in a wide variety of patient populations [10,25,31].”
In the citing paper
“Statins are currently the most effective agents available for managing dyslipidemia and have been shown to reduce CV events in a wide variety of patient populations [10,25,31].”
In the citing paper
“Assiduous attention to abnormalities other than hyperglycemia that accompany type 2 diabetes, such as hypertension and dyslipidaemia, has been shown to improve microvascular and cardiovascular complications.”
From Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy (2009) · cites this paper as [21]
In the citing paper
“Nevertheless, measurement and treatment of blood lipids, blood pressure, and glucose levels have became the major emphases for cardiovascular risk reduction.”
From Beyond Established and Novel Risk Factors: Lifestyle Risk Factors for Cardiovascular Disease (2008) · cites this paper as [25]
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Metadata
- Authors
- Grundy, S. M., Cleeman, J. I., Merz, C. N. B., Brewer, H. B., Clark, L. T., Hunninghake, D. B., Pasternak, R. C., Smith, S. C., & Stone, N. J.
- Affiliations
- American College of Cardiology (US)
- Venue
- Circulation
- Published
- 2004-07-13
- Volume
- 110
- Issue
- 2
- Pages
- 227-239
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2106343349
- Cited by
- 6,902
- References
- 54
- Citations by year
- 2026: 32 · 2025: 44 · 2024: 72 · 2023: 71 · 2022: 85 · 2021: 100 · 2020: 127 · 2019: 137 · 2018: 152 · 2017: 189 · 2016: 248 · 2015: 324 · 2014: 382 · 2013: 506 · 2012: 489
- FWCI
- 539.21
- Type
- journal article
- Language
- en
- Update notices
- correction (2004-08-10)
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- American Heart Association
- American College of Cardiology Foundation
- National Heart, Lung, and Blood Institute
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- Adult Treatment Panel III, LDL cholesterol targets, statin therapy, cholesterol-lowering therapy, diabetes mellitus, older adults, triglycerides, HDL cholesterol, nicotinic acid, therapeutic lifestyle changes, cardiovascular risk stratification, hypercholesterolemia, metabolic syndrome, cardiovascular disease prevention
- MeSH terms
- Aged, Anticholesteremic Agents, Antihypertensive Agents, Hypolipidemic Agents, Cardiovascular Diseases, Clinical Trials as Topic, Diabetes Mellitus, Humans, Hypercholesterolemia, Hypertension, Cholesterol, LDL, Middle Aged, Myocardial Infarction, Patient Education as Topic, Risk, Risk Factors, Comorbidity, Thrombolytic Therapy, Randomized Controlled Trials as Topic, Practice Guidelines as Topic, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Evidence-Based Medicine
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