NCEP ATP IV GUIDELINES:

2013 UPDATE

Learning Objectives
1. List three anticipated changes to the ATP IV guidelines

2. Compare and contrast two validated risk assessment

tools used to stratify risk of developing cardiovascular disease and individualize LDL-c goals 3. Describe the primary treatment targets from the ATP III guidelines and potential changes for ATP IV

National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) Guidelines
U.S. guidelines for the detection, evaluation, and

treatment of hyperlipidemia in adults Developed by an expert panel for the National Heart, Lung, and Blood Institute (NHLBI)
Division of National Institutes of Health (NIH)
Long history of developing clinical practice guidelines
First JNC report published 1976

ATP release history: ATP I First released in 1988 ATP II 1993 ATP III 2001

For more information or to check status: http://www.nhlbi.nih.gov/guidelines/indevelop.htm

Potential Changes for ATP IV

Current guidelines ATP III
Focus on LDL-c Greatest intensity of treatment for patients at highest risk

Other dyslipidemia management guidelines

Changes in LDL-c targets for those at highest risk Some modifications of risk factors

Direction from expert panel for ATP IV Critical questions

Scientific evidence from clinical trials

U.S. Guidelines for Management of Dyslipidemias

2001 2004 2008 NCEP ATP III guidelines NCEP ATP III implications ADA/ACCF Consensus Statement on Lipoprotein Management in Patients with Cardiometabolic Risk AHA/ACC guidelines for secondary prevention AACE Guidelines for the Management of Dyslipidemia and Prevention of Atherosclerosis ADA Standards of Medical Care in DM

2011 2012 2013

AACE = American Association of Clinical Endocrinologists, ACC = American College of Cardiology, ACCF = American College of Cardiology Foundation, ADA = American Diabetes Association, AHA= American Heart Association

Critical Questions for ATP IV

What evidence supports LDL-c goals for secondary prevention? What evidence supports LDL-c goals for primary prevention? What is the impact of the major cholesterol drugs on efficacy/safety in the populations?

Overview of Potential Changes for ATP IV

Modification of CVD Risk Estimation Adjustment of major risk factors and CHD risk equivalents Alternative risk assessment tool to Framingham Risk Score (FRS) Changes in Treatment Targets Changes in LDL-c goals
More aggressive treatments in those at elevated risk of CHD

Changes in target emphasis

Recommended Pharmacologic Treatment Continued use of statins at optimal dosing Highlight lack of CV outcome evidence for adjunctive therapies

ATP III Classification of Cholesterol Concentrations

Lipoprotein TC Concentration (mg/dL) < 200 200-239 240 <100 100-129 130-159 160-189 190 <40 60 <150 150-199 200-499 500 Interpretation Desirable Borderline high High Optimal Near/above optimal Borderline high High Very high Low High Normal Borderline high High Very high

LDL-c

HDL-c TG

ATP III Treatment Targets

Secondary Target: Non-HDL-c
(Once LDL goal met and if TG 200)

Primary Target: LDL-c

Exception: TG lowering is an immediate target if 500 mg/dL

NCEP ATP III: Determining LDL-c Goals

Presence of ASVD, DM
Yes No

2 major CV risk factors*

Yes

No

10-year CHD risk: FRS

High-Risk: <100mg/dL, optional <70mg/dL

>20%

10-20%

<10%

High-Risk: <100mg/dL

Mod-high Risk: <130mg/dL, optional <100mg/dL

Moderate risk <130mg/dL

Lower risk <160mg/dL

ATP III 2004 Implications

Very high risk definition: Presence of CVD plus:
Multiple major risk factors (DM) Severe and poorly controlled risk factors (smoking) Metabolic syndrome ACS

Optional goal of LDL-c < 70

Potential Change for ATP IV

CHD Risk Equivalents
Chronic kidney disease (CKD) Potentially added as a CHD risk equivalent
Increased risk of CHD and premature CHD Evidence suggests patients with CKD have expected 10-yr risk CHD >

20%
Guidelines
National Kidney Foundation (NKF) Kidney Disease Outcomes Quality

Initiative (K/DOQI) Group 2003 AHA supported recommendation 2003

NCEP ATP III: Determining LDL-c Goals

Presence of ASVD, DM
Yes No

2 major CV risk factors*

Yes No

10-year CHD risk: FRS

High-Risk: <100mg/dL, optional <70mg/Dl

>20%

10-20%

<10%

High-Risk: <100mg/dL

Mod-high Risk: <130mg/dL, optional <100mg/dL

Moderate risk <130mg/dL

Lower risk <160mg/dL

ATP III Risk Stratification for LDL-c Goal

Determine presence of other major risk factors Age
Men45 Women 55

Family history of premature CHD

First degree relative with heart disease in males before 55 or women before 65

Hypertension
140/90 or on antihypertensive medications

Cigarette smoking Low HDL

< 40mg/dL* (negative risk factor if HDL > 60)

If 2 or more risk points are present, then calculate FRS

NCEP ATP III: Determining LDL-c Goals

Presence of ASVD, DM
Yes No

2 major CV risk factors*

Yes No

10-year CHD risk: FRS

High-Risk: <100mg/dL, optional <70mg/Dl

>20%

10-20%

<10%

High-Risk: <100mg/dL

Mod-high Risk: <130mg/dL, optional <100mg/dL

Moderate risk <130mg/dL

Lower risk <160mg/dL

Framingham Risk Assessment Tool

Background Derived from the Framingham Heart Study Validated method to predict 10-year risk of hard coronary heart disease (nonfatal MI or coronary death) Used in those without ASVD or risk equivalents (DM) Score Low <10%, Moderate 10-20%, High >20% Limitations Predicts risk best
ages 30-65

Less precise in those with diabetes, pre-diabetes, severe HTN, LVH, younger

men and women, and some racial groups Japanese-Americans, Hispanic men, and Native American women. Limited to estimation of 10-year risk Available http://www.nhlbi.nih.gov/guidelines/cholesterol/atglance.pdf http://hp2010.nhlbihin.net/atpiii/calculator.asp

Framingham Risk Assessment Tool

Alternative Risk Assessment Tools

Reynolds Risk Assessment (RRS) Tool has been developed to improve 10-year risk estimation FRS may underestimate risk in the young and in women who are classified as low risk Utilizes 7 risk factors:
age, SBP, TC, HDL-c, smoking hs-CRP <1 mg/L low, 1-3 mg/L (intermediate), >3 mg/L (high risk) parental history of premature MI

An optional assessment tool in the Canadian Cardiovascular

Society guidelines 2009 and 2012 AACE Dyslipidemia Guidelines www.reynoldsriskscore.org

NCEP ATP III: Determining LDL-c Goals

Presence of ASVD, DM
Yes No

2 major CV risk factors*

Yes No

10-year CHD risk: FRS

High-Risk: <100mg/dL, optional <70mg/Dl

>20%

10-20%

<10%

High-Risk: <100mg/dL

Mod-high Risk: <130mg/dL, optional <100mg/dL

Moderate risk <130mg/dL

Lower risk <160mg/dL

Anticipated Changes to LDL-c Goals

Optional goals will become new treatment goals LDLc goal < 70 for very high risk High risk and moderate risk less clear Several clinical trials have shown consistent reduction in CHD

events (patients with CHD or ACS) when achieving LDL-c of 60-80mg/dL compared to LDL-c levels of 100mg/dL
PROVEIT-TIMI22, A-to-Z, TNT, IDEAL

One study has also shown coronary atheroma regression when

LDL-c levels are lowered below 80mg/dL (average 60.8mg/dL) with high potency statins
Asteriod

Two studies have shown continuous risk reduction in patients

with moderate risk taking statins

ASCOT, JUPITER

ADA/ACCF Consensus Statement

Lipoprotein Management in Patients with Cardiometabolic Risk
LDLc (mg/dL) Very High Risk Established CVD DM and 1 major CVD risk factors* High Risk No CVD and 2 major CVD risk factors* DM and no major CVD risk factors*
*Risk factors: dyslipidemia, smoking, HTN, family history of premature CAD

Non-HDLc (mg/dL)

Apo B (mg/dL)

<70

<100

<80

<100

<130

<90

Brunzell JD, et al. Diabetes Care 2008; 31:811-22

AACE LDLc Treatment Goals

Risk Category Very High Risk Patient Population Established or recent hospitalization for coronary, carotid or peripheral vascular disease DM with additional risk factors LDLc (mg/dL) < 70

High Risk

2 major risk factors and FRS > 20% CHD risk equivalent

< 100

Moderately High Risk

2 major risk factors and FRS 10-20%

<130

Moderate Risk

2 major risk factors and FRS < 10%

< 130

Low Risk

risk factor

< 160

CHD risk equivalent = DM, PAD, AAA, CAD

Endocr Pract. 2012; 18 (Suppl 1)

Treatment Strategies
Statins Recommended first line: Most robust data for efficacy in reducing CHD events LDL lowering with statin therapy correlates with 30-35% CVD relative risk reduction Lowers LDL 21-63% Pleiotropic effects

Improves endothelial function Inhibits platelet aggregation Decreases LDL oxidation Reduces vascular inflammation Stabilizes atherosclerotic plaques

CV event reduction has been disappointing when adding on

other lipid lowering therapies

Enhance, SEAS statin plus ezetimibe AIM-HIGH statin plus niacin ACCORD fenofibrate plus simvastatin (in DM)