NCEP ATP IV Guidelines: Whats New in 2012?

NCEP ATP IV GuidelineS: 2013 Update

The National Cholesterol Education Program Adult Treatment Panel guidelines, national guidelines for the management of dyslipidemias in adults.

The last update, ATP III, were released in 2001. ATP IV was originally scheduled for release in 2009, but there have been many factors involved with the delays.

This session will focus on the current development process for ATP IV, potential areas of change for those guidelines, and some practice changes that have already been occurring based on research evidence over the past decade.

1Learning ObjectivesList three anticipated changes to the ATP IV guidelinesCompare and contrast two validated risk assessment tools used to stratify risk of developing cardiovascular disease and individualize LDL-c goalsDescribe the primary treatment targets from the ATP III guidelines and potential changes for ATP IVReview ATP III recommendations and compare to potential areas of change.2National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) GuidelinesU.S. guidelines for the detection, evaluation, and treatment of hyperlipidemia in adultsDeveloped 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 guidelinesFirst JNC report published 1976ATP release history:ATP I First released in 1988ATP II 1993ATP III 2001

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For more information or to check status:http://www.nhlbi.nih.gov/guidelines/indevelop.htmThis process has been taking a very long time and began in 2005. The review process has become much more complicated this time.

Used a new methodology to comprehensively review of the literature and systematically evaluate the evidence Eliminate forms of bias (expert opinion) Develop an integrated set of cardiovascular risk reduction guidelines (HTN, Obesity, lifestyle, CV risk assessment)4. Perhaps some delay to review results of some major trials due to be completed in 2013. Studies: HPS2-Thrive : Treatment of HDL to reduce incidence of vascular events simva plus high dose Niacin ER. Results expected in 2013, Dal-outcomes, Reveal, Improve-IT

To check status: check website

Cholesterol, Risk assessment and lifestyle guidelines in draft form, have completed federal and expert review and are currently being reviewed by NHBLI advisory council, who will then review, comment and recommend approval.

Next step is to be released for public comment. Process takes roughly six months and then final guidelines are published.

4Potential Changes for ATP IVCurrent guidelinesATP IIIFocus on LDL-c Greatest intensity of treatment for patients at highest riskOther dyslipidemia management guidelinesChanges in LDL-c targets for those at highest riskSome modifications of risk factorsDirection from expert panel for ATP IVCritical questionsScientific evidence from clinical trials

ATP III LDL will remain a primary target. There is a log-linear relationship between LDL-c levels and relative risk for CHD. Numerous RCT have demonstrated the reduction of LDL reduces CHD risk in primary and secondary prevention and in angiographic trials.

Growing evidence to show targeting LDLc is not the complete picture. 5U.S. Guidelines for Management of Dyslipidemias2001NCEP ATP III guidelines 2004NCEP ATP III implications2008ADA/ACCF Consensus Statement on Lipoprotein Management in Patients with Cardiometabolic Risk2011AHA/ACC guidelines for secondary prevention2012 AACE Guidelines for the Management of Dyslipidemia and Prevention of Atherosclerosis2013ADA Standards of Medical Care in DM

AACE = American Association of Clinical Endocrinologists, ACC = American College of Cardiology, ACCF = American College of Cardiology Foundation, ADA = American Diabetes Association, AHA= American Heart Association2001- Updated ATP II 1. lowered TG goal < 150 and raised HDL cut points2. DM became a CV risk equivalent3. FRS used further identify those at risk and stratify treatment4. Non-HDL was identified as a secondary target for those with elevated TG >200

2004 recommendations to modify ATP III goals based on results of several (5) clinical trials with statin therapy. Established optional goals for very high risk individuals or those moderately high risk with FRS 10-20

ADA/ACCF Lipid goals for patients with cardiometabolic risk (HTN, obesity, IR, abnormal lipid metabolism, family history, inflammation/hypercoagulability) more stringent goals for very high risk LDL< 70, non-HDL < 100 apo B < 80, high risk LDL< 100, apo < 90 (similar to optional goals from 2004 ATP III update.)

AHA/ACC 2nd prevention in those with ASVD. This panel is Planning to review their recommendations when ATP guidelines are released. States that LDL goal < 70 is reasonable for very high risk patients (C)

AACE -1.Recommends lower LDL goals for very high and high risk patients. 2. Recommend patients with pre-DM have same treatment goals as DM pts.3. Recommends FRS or RRS. 4. these guidelines support use of apo B or LDL particle number to further assess residual risk in patients with TG > 150 and HDL < 40.

ADA updated annually. Goals are same as 2004 NCEP update. Recommend expanded statin use in DM with CHD regardless of baseline lipids and for DM > 40 with 1 risk factor.

6Critical Questions for ATP IVWhat 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?

AHA Scientific Sessions in Nov 2011, chairs from each expert committee presented prioritized list of critical questions which will be used as the basis for recommendations

#1 Looking at evidence in subpopulations: Women, DM, metabolic syndrome, CKD, smokers, LDLc 20, men/women, ethnicity

#3 efficacy at different LDL, TG, HDL cut points and safety in different populations: transplant, HIV +/- PIs

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Before we discuss the changes, lets review the major classes of lipoproteins and role in atherogenesis.

Cholesterol is a relatively water-insoluble molecule, so it is packaged with TG and phospholipids into a carrier protein called a lipoprotein which is water-soluble and allows for transportation of cholesterol in the blood.

Lipoprotein vary in size and density with regard to fat and protein content. The major lipoproteins are listed here based on size.

HDL Good cholesterol. Involved in reverse cholesterol transport -Acquires cholesterol from the bodys tissues and promotes efflux from foam cells from AS lesions and transports it back to the liver. Also has antioxidant and antiinflammatory properties, protects LDL from oxidation- that inhibit atherogenesis. Raising HDL through targeted drug therapy has not proven to show benefit, current evidence does not support practice.

LDL-c is responsible for transporting cholesterol from the liver to cells throughout the body and carries up 60-70% of TC. It is the most atherogenic of the lipoproteins. When levels are in excess, LDL readily enters arterial wall and accumulates leading to atherogenic changes. Different densities. Small, dense LDL is assoc with increased risk of CVD. May migrate into the arterial wall more readily and are more susceptible to oxidation. It is preferred to have an LDL pattern with more large buoyant molecules light, fluffy compared to small and dense. May have normal LDL levels, but increased number of small dense LDL particles.

IDL: precursor to LDL, number included in LDL in a cholesterol panel.

Very low density lipoproteins (VLDL) are also TG rich, Are a precursor to LDL. VLDL reminants are atherogenic another type of bad cholesterol

Chylomicrons are TG-rich lipoproteins that are formed following consumption of dietary fat. Not normally present in plasma after a 12 hour fast.

Lipoproteins carry different types of surface apolipoproteins which direct the processing and removal of lipoprotein particles. Apolipoprotein B are contained on the surface of lipoproteins that are atherogenic (LDL, VLDL, IDL, Lp (a) and chymlomicrons) while HDL carries - Apolipoprotein A.

If we just look and measure the LDL cholesterol, part of the picture may be missing.

Non-HdL number TC HDL = estimates total atherogenic, apo B containing cholesterol (to further reduce risk)

8Overview of Potential Changes for ATP IV Modification of CVD Risk EstimationAdjustment of major risk factors and CHD risk equivalentsAlternative risk assessment tool to Framingham Risk Score (FRS)Changes in Treatment TargetsChanges in LDL-c goalsMore aggressive treatments in those at elevated risk of CHDChanges in target emphasisRecommended Pharmacologic TreatmentContinued use of statins at optimal dosingHighlight lack of CV outcome evidence for adjunctive therapies

There are several projections for changes for ATP IV recommendations based on research, other available guidelines and expert opinion

Add-on therapies will further reduce LDL, but generally insignificant reduction in CV events

9ATP III Classification of Cholesterol ConcentrationsLipoproteinConcentration (mg/dL)InterpretationTC< 200200-239240DesirableBorderline highHighLDL-c