New Lipid GuidelinesWhat Has Changed ?

Atherosclerosis and Metabolic Syndrome Units,2nd Prop Clinic of Internal Medicine,

Aristotelian University, Hippocration Hospital, Thessaloniki, Greece

V.G ATHYROS, MD, FESC, FRSPH, FASA, FACS

Treatment of Hyperlipidemia

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.

High LDL-C

Therapeutic Lifestyle Change

Drug Therapy

Therapy of Choice: Statin

Alternative: Resin or niacin

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.

2001 NCEP ATP III Treatment Categories, LDL-C Goals and Cutpoints

Risk Category LDL-C GoalConsider Drug

Therapy

CHD or CHD risk equivalent <100 mg/dL 130 mg/dL*

2 Risk Factors

10-yr risk 10–20%

10-yr risk <10%

<130 mg/dL

<130 mg/dL

130 mg/dL

160 mg/dL

<2 Risk Factors <160 mg/dL 190 mg/dL

* 100–129 mg/dL = after TLC, consider statin, niacin, or fibrate therapy

Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA): Study Design

• Nonfatal MI, including silent MI, and fatal CHD

Primary efficacy end point

HTN=hypertension; SBP=systolic blood pressure; DBP=diastolic blood pressure; TC=total cholesterol;

CVD=cardiovascular disease.

Sever PS et al. Lancet. 2003;361:1149-1158.

• Men and women aged 40-79 years

• Untreated HTN (SBP 160 mm Hg, DBP 100 mm Hg, or both)

• Treated HTN (SBP 140 mm Hg, DBP 90 mm Hg, or both)

• TC 251.4 mg/dL

• At least 3 additional CVD risk factors

Atorvastatin 10 mg(n=5168)

Placebo

(n=5137)

Patient population

5 years

19,342

patients

with HTN

10,305

patients with

TC 251.4 mg/dL

•Trial stopped at 3.3 years,

2 years earlier than expected

0

1

2

3

4

0,0 0,5 1,0 1,5 2,0 2,5 3,0 3,5

Έτη

Aθρ

οισ

τική

συ

χνό

τητα

36% Reduction

ASCOT: Πρωτεύον Τελικό Σημείo: Non-fatal MI – CVD death

HR = 0.64 (0.50-0.83)

Atorvastatin 10 mg Number of CVD events 100

Placebo Number of CVD events 154

p=0.0005

Sever PS, et al, for the ASCOT Investigators. Lancet. 2003;361:1149-58

LDL=130 mg/dl

LDL=90 mg/dl

NCEP ATP III: 2004 Updated LDL-C Goals, Treatment Cutpoints

Risk Category LDL-C Goal Initiate TLCConsiderDrug Therapy

Lower risk:0–1 risk factor

<160 mg/dL 160 mg/dL 190 mg/dL

Moderate risk:2 risk factors(10-year risk<10%)

<130 mg/dL 130 mg/dL 160 mg/dL

Moderatelyhigh risk:2 risk factors(10-year risk 10%–20%)

High risk:CHD or CHD risk equivalents*

(10-year risk >20%)

<130 mg/dLoptional:

<100 mg/dL

<100 mg/dL

optional:

<70 mg/dL

130 mg/dL

100 mg/dL

130 mg/dL(100–129 mg/dL: consider drug options)

100 mg/dL(<100 mg/dL: consider drug options)

Endpoint Studies: Treating to New Targets (TNT): Study Design

Site SelectionNovember 1997

InvestigatorMeeting

March 1998

RecruitmentCompleteJune 1999

Study EndDec 2004

Atorvastatin10 mg

LDL75 mg/dL

LDL100 mg/dL

5 Years

Atorvastatin80 mg

10,000 CAD Patients

TNT: Major CHD events

LaRosa JC et al. N Engl J Med. 2005;352.

22% RRR

Years

65421 3

Atorvastatin 10 mg

Atorvastatin 80 mg

0

0.00

Major CHD event (%)

0.05

0.10

0.15

HR = 0.78 (0.69–0.89)P < 0.001

Death, non-fatal MI, cardiac arest, stroke.

TNT: Stroke

LaRosa JC et al. N Engl J Med. 2005;352.

25% RRR

Years

65421 3

Atorvastatin 10 mg

Atorvastatin 80 mg

0

0.00

Stroke (%) 0.02

0.04

0.01

0.03

HR = 0.75 (0.59–0.96)P = 0.02

TNT diabetes analysis:Major CHD events

Shepherd J. American Diabetes Association 2005 Scientific Sessions; June 10-14, 2005; San Diego, CA.

25% RRR

Years

65421 3

Atorvastatin 10 mg (n= 753)

Atorvastatin 80 mg(n= 748)

0

0.00

(%) 0.10

0.20

0.05

0.15

HR = 0.75, P = 0.026

N=1.500

TNT diabetes analysis: Stroke

Shepherd J. American Diabetes Association 2005 Scientific Sessions; June 10-14, 2005; San Diego, CA.

31% RRR

Years

65421 3

Atorvastatin 10 mg (n= 753)

Atorvastatin 80 mg(n= 748)

0

0.00

(%)

0.05

0.10

HR = 0.69, P = 0.037

N=1.5000.15

The Need to Implement Secondary Prevention

Multiple studies of the use of these recommended therapies in appropriate patients continue to show that many patients in whom therapies are indicated are not receiving them in actual clinical practice

The AHA and ACC urge that in all medical care settings where these patients are managed that programs be implemented to provide practitioners with useful reminder clues based on the guidelines and to continuously assess the success achieved in providing these therapies to the patients who can benefit from them.

Encourage that the AHA’s Get With the Guidelines and/or ACC’s Guidelines Applied to Practice Programs be instituted to identify appropriate patients for therapy

AHA=American Heart AssociationACC=American College of Cardiology

Care Gap

AHA Get With The Guidelines (GWTG) Program

GWTG is a national initiative of the AHA to improve guidelines adherence in patients hospitalized with cardiovascular disease

GWTG uses collaborative learning sessions, conference calls, e-mail and staff support to assist hospital teams improve acute and secondary prevention care systems

A web-based Patient Management Tool is used for point-of-care data collection and decision support, on-demand reporting, communication, and patient education

Get With The Guidelines Hospital Tool Kit. Dallas, TX: American Heart Association 2006.

AHA=American Heart Association

Athyros V, et al. Curr Vasc Pharmacol 11 April 2011

95

96

97

98

99

100

0 6 12 18 24 30 36 42

Group A Group B

Δ%

Event free survival

Months

p=0.0012

ATTEMPT

Guidelines for the Diagnosis

and Treatment of Dyslipidemia

and Prevention of

Cardiovascular Disease 2009

Risk Level Initiate treatment if: Primary PrimaryLDL-C Alternate

High Consider treatment in all

patients

CAD,PVD

Atherosclerosis

Most Pts with Diabetes

FRS ≥ 20%, RRS ≥ 20%

<2 mmol/L Or ↓50% LDL-C ApoB<0.80Class I Level A Class I Level A

Moderate (strive towards )

FRS 10-19% LDL-C>3.5 mmol/L

TC/HDL >5.0

hsCRP >2

men 50+, women 60+

Family history and hsCRP modulate

risk

<2 mmol/L Or ↓50% LDL-C ApoB<0.80Class IIA Level A Class IIA Level A

LowFRS<10% LDL-C>5.0mmol/L

↓50% LDL-C

Στόχοι LDL-C κατά τισ Καναδικζσ κατευθυντήριεσ οδηγίεσ

A A

A A

A

Genest J et al. Can J Cardiol 2009 Oct;25(10):567-79

European Guidelines 2011

European Guidelines 2011

Η LDL-C remains the main therapeutic target

European Guidelines 2011

European guidelines on cardiovascular disease prevention in clinical practice: Third Joint Task Force of European and other Societies on

Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of eight societies and by invited experts)

Greek Guidelines for the Treatment of Dyslipidaemia

Level of risk for statin treatment initiation

LDL-C target

High

CHDStrokePADType 2 DM or Type 1 > 40 yearsCKD with GFR <60 ml/minFramingham score >20%

<70 mg/dlorLDL CHOL κατά 50%

MediumAt leas 2 CVD risk factors

Framingham score 10%-20%

<100 mg/dl

Low0-1 CVD risk factors without CVDFramingham score <10%

< 130 mg/dl

Greek Atherosclerosis Society 2011

Relationship Between Estimated GFR (eGFR) and Clinical Outcomes

Go AS, et al. N Engl J Med 2004;351:1296-305

Ag

e-s

tan

dard

ized

even

t ra

te (

per

100 p

ers

on

-yr) Death from any cause Cardiovascular events Any hospitalization

Total events = 51,424 Total events = 139,011 Total events = 554,651

Kaiser Permanente Renal Registry, n=1,120,295 adults aged 20 years Median follow-up = 2.84 years

eGFR (mL/min/1.73 m2)

Total cardiovascular risk should

not be shaped by LDL-C levels onlybut

it should define the LDL-C target

Treatment of Mixed Hyperlipidemia(Residual Cardiovascular Risk Reduction)

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.

High LDL-C and TGs

Therapeutic Lifestyle Change

Drug Therapy

Achieve the LDL-C goal1STEP

Achieve the non-HDL-C goalIncrease LDL-C lowering orAdd a fibrate, niacin or fish oils

2STEP

R3i: Τοπικζσ οργανώςεισ ςε εθνικό επίπεδο

27

UK

Italy

Bulgaria

Slovakia

China

Thailand

Croatia

Malaysia

Kuwait

Spain

Algeria

Qatar 3

Philippines

Poland

Portugal

Lituania

Singapore

Romania

UAE

Czech R

Greece

Russia

Latvia

Hungary

Indonesia

Ireland

Hong Kong

South Africa

Japan

France

Saudi Arabia

MexicoKorea

Jordan

Taiwan

Germany

Switzerland

Turkey

Egypt

Australia

South America ( in development)

Austria

Canada

Belgium

Vietnam

US

Morocco Tunisia

Emirates

Guidelines that

aren’t implemented

don’t work