Implications of Recent Clinical Trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines
Scott M. Grundy; James I. Cleeman; C. Noel Bairey Merz; H. Bryan Brewer, Jr.; Luther T. Clark; Donald B. Hunninghake; Richard C. Pasternak; Sidney C. Smith, Jr.; Neil J. Stone; for the Coordinating Committee of the National Cholesterol Education Program
The Adult Treatment Panel (ATP III) of the National Cholesterol Education Program issued an evidence-based set of guidelines on cholesterol management in 2001
Implications of Recent Clinical Trials for the NCEP ATP III Guidelines
Background
Grundy, S. et al., Circulation 2004;110:227-39.
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
Background
Grundy, S. et al., Circulation 2004;110:227-39.
Implications of Recent Clinical Trials for the NCEP ATP III Guidelines
To review the results of these recent trials and assess their implications for cholesterol management
Objective
Grundy, S. et al., Circulation 2004;110:227-39.
Implications of Recent Clinical Trials for the NCEP ATP III Guidelines
Log-Linear Relationship Between LDL-C Levels and Relative Risk for CHD
3.7
2.9
2.2
1.7
1.3
1.0
40 70 100 130 160 190
Relative Risk for Coronary Heart Disease (Log Scale)
LDL-Cholesterol (mg/dL)
Grundy, S. et al., Circulation 2004;110:227-39.
Doses of Currently Available Statins Required to Attain an Approximate 30% to 40% Reduction of LDL-C Levels (Standard Doses)
Grundy, S. et al., Circulation 2004;110:227-39.
? All of these are available at doses up to 80 mg. For every doubling of the dose above the standard dose, an approximate 6% decrease in LDL-C level can be obtained.
? For rosuvastatin, doses available up to 40 mg; the efficacy for 5 mg is estimated by subtracting 6% from the FDA reported efficacy at 10 mg
ATP III LDL-C Goals and Cutpoints for TLC and Drug Therapy in Different Risk Categories and Proposed Modifications Based on Recent Clinical Trial Evidence
Grundy, S. et al., Circulation 2004;110:227-39.
Therapeutic lifestyle changes (TLC) remain an essential modality in clinical management
TLC have the potential to reduce CV risk through several mechanisms beyond LDL lowering
Recommendations for Modifications to Footnote the ATP III Treatment Algorithm for LDL-C
Grundy, S. et al., Circulation 2004;110:227-39.
Overview of Recommendations
Recommended LDL-C goal is <100 mg/dL
An LDL-C goal of <70 mg/dL is a therapeutic option on the basis of available clinical trial evidence, especially for patients at very high risk
If LDL-C is ?100 mg/dL, an LDL-lowering drug is indicated simultaneously with lifestyle changes
Grundy, S. et al., Circulation 2004;110:227-39.
High-Risk Persons
Recommendations for Modifications to Footnote the ATP III Treatment Algorithm for LDL-C
Recommended LDL-C goal is <100 mg/dL
If baseline LDL-C is <100 mg/dL, institution of an LDL-lowering drug to achieve an LDL-C level <70 mg/dL is a therapeutic option on the basis of available clinical trial evidence
Grundy, S. et al., Circulation 2004;110:227-39.
High-Risk Persons
Recommendations for Modifications to Footnote the ATP III Treatment Algorithm for LDL-C
Recommended LDL-C goal is <100 mg/dL
If a high-risk person has high triglycerides or low HDL-C, consideration can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug
When triglycerides are ?200 mg/dL, non-HDL-C is a secondary target of therapy, with a goal 30 mg/dL higher than the identified LDL-C goal
Grundy, S. et al., Circulation 2004;110:227-39.
High-Risk Persons
Recommendations for Modifications to Footnote the ATP III Treatment Algorithm for LDL-C
Recommended LDL-C goal is <130 mg/dL
An LDL-C goal <100 mg/dL is a therapeutic option on the basis of available clinical trial evidence
Grundy, S. et al., Circulation 2004;110:227-39.
Moderately High-Risk Persons
Recommendations for Modifications to Footnote the ATP III Treatment Algorithm for LDL-C
Recommended LDL-C goal is <100 mg/dL
When LDL-C level is 100 to 129 mg/dL, at baseline or on lifestyle therapy, initiation of an LDL-lowering drug to achieve an LDL-C level <100 mg/dL is a therapeutic option on the basis of available clinical trial evidence
Grundy, S. et al., Circulation 2004;110:227-39.
Moderately High-Risk Persons
Recommendations for Modifications to Footnote the ATP III Treatment Algorithm for LDL-C
Any person at high risk or moderately high risk who has lifestyle-related risk factors (e.g., obesity, physical inactivity, elevated triglyceride, low HDL-C, or metabolic syndrome) is a candidate for TLC to modify these risk factors regardless of LDL-C level
Grundy, S. et al., Circulation 2004;110:227-39.
High Risk/Moderately High-Risk Persons
Recommendations for Modifications to Footnote the ATP III Treatment Algorithm for LDL-C
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
Grundy, S. et al., Circulation 2004;110:227-39.
High Risk/Moderately High-Risk Persons
Recommendations for Modifications to Footnote the ATP III Treatment Algorithm for LDL-C
For people in lower-risk categories, recent clinical trials do not modify the goals and cutpoints of therapy
Grundy, S. et al., Circulation 2004;110:227-39.
Lower-Risk Persons
Recommendations for Modifications to Footnote the ATP III Treatment Algorithm for LDL-C