Aggressive Therapy of Hypercholesterolemia in Acute Coronary Syndromes Timothy A. Denton, M.D....

Aggressive Therapy of Aggressive Therapy of Hypercholesterolemia inHypercholesterolemia in

Acute Coronary SyndromesAcute Coronary Syndromes

Aggressive Therapy of Aggressive Therapy of Hypercholesterolemia inHypercholesterolemia in

Acute Coronary SyndromesAcute Coronary Syndromes

Timothy A. Denton, M.D.Timothy A. Denton, M.D.

Divisions of Cardiology and Cardiothoracic SurgeryDivisions of Cardiology and Cardiothoracic Surgery

Cedars-Sinai Medical Center, Los Angeles, CACedars-Sinai Medical Center, Los Angeles, CA

California Chairman, AHA "Get with the Guidelines"California Chairman, AHA "Get with the Guidelines"

Who are we talking about?• Known vascular disease

CADCarotidPVDAortic Aneurysm

• Vascular equivalentsDM

• High risk10 year risk > 20%

NCEP III -- JAMA 2000;285:2486

LDL Cholesterol Goals and Cutpoints for Therapeutic LDL Cholesterol Goals and Cutpoints for Therapeutic Lifestyle Changes (TLC)Lifestyle Changes (TLC)

and Drug Therapy in Different Risk Categoriesand Drug Therapy in Different Risk Categories

LDL Cholesterol Goals and Cutpoints for Therapeutic LDL Cholesterol Goals and Cutpoints for Therapeutic Lifestyle Changes (TLC)Lifestyle Changes (TLC)

and Drug Therapy in Different Risk Categoriesand Drug Therapy in Different Risk Categories

190 190 (160–189: LDL-(160–189: LDL-

lowering drug optional)lowering drug optional)160160<160<1600–1 Risk Factor0–1 Risk Factor

10-year risk 10–20%: 10-year risk 10–20%: 130130

10-year risk <10%: 10-year risk <10%: 160 160

130130<130<1302+ Risk Factors 2+ Risk Factors

(10-year risk (10-year risk 20%)20%)

130 130 (100–129: drug (100–129: drug

optional)optional)100100<100<100

CHD or CHD Risk CHD or CHD Risk EquivalentsEquivalents

(10-year risk >20%)(10-year risk >20%)

LDL Level at Which LDL Level at Which to Considerto Consider

Drug Therapy Drug Therapy (mg/dL)(mg/dL)

LDL Level at Which to LDL Level at Which to Initiate Therapeutic Initiate Therapeutic Lifestyle Changes Lifestyle Changes

(TLC) (mg/dL)(TLC) (mg/dL)LDL GoalLDL Goal(mg/dL)(mg/dL)Risk CategoryRisk Category

1 - Diet2 - Exercise3 - Drugs4 - Partial ileal bypass5 - Portacaval shunting6 - Apheresis

adsorption column (LDL apheresis)plasma exchangedouble membranedextran sulfate precipitationimmunoabsorption

7 - Liver transplantation

Methods for Modifying Cholesterol Levels

Atherosclerosis

Egg McMuffin

Calories 290Calories from fat 110Total fat 12 gSaturated fat 4.5 gCholesterol 235 mgSodium 790 mgCarbohydrates 27gProtein 17g

http://www.mcdonalds.com/countries/usa/

Ornish D, et al. Lancet 1990;336:129

Lifestyle Heart Trial

Changes in Fat Intake

31.5

6.8

30.1 29.5

0

5

10

15

20

25

30

35

40

45

50

Baseline 1 year

Die

tary

Per

cen

t F

at

Ornish D, et al. Lancet 1990;336:129

Lifestyle Heart Trial

Change in Serum Lipids(Intervention Group)

222

168

148

93

38 37

90110

0

50

100

150

200

250

Baseline 1 year

Die

tary

Per

cent

Fat

TCholLDLHDLTG

Ornish D, et al. Lancet 1990;336:129

Lifestyle Heart TrialIntervention group LDL after 1 year

0

5

10

15

20

25

30

0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200

Serum LDL Cholesterol (mg/dl)

Mean = 93 mg/dl + 43 mg/dl

NCEP Goal

55.3% 44.7%

Mediterranian Diet

J. THOMSON "Chart of the Mediterranean Sea" Edin.18I7

Lyon Heart Trial

De Lorgeril et al Circulation 1999;99:779

•First MI•Randomized•Mediterranian vs Prudent•5 year trial stopped early

• <35% energy as fat• <10% energy saturated fat• <4% energy as linoleic acid• >0.6% of energy as alpha-linolenic (18:3 or n-3)

• Eat more bread• Eat more fish, less meat• Eat more vegetables• Must have fruit every day• All butter and margarine replaced with olive oil and canola oil

Lyon Heart Trial

De Lorgeril et al Circulation 1999;99:779

Survival with:No MI

Survival with:No MIAnginaCHFCVAPEPeriph embol

Survival with:No MIAnginaCHFCVAPEPeriph embolStable anginaPTCA, CABGRestenosis

Control(n=204)

Intervention(n=219)

LDL 4.23 mmol/L163.6 mg/dL

4.17 mmol/L161.3 mg/dL

Lyon Heart Trial

De Lorgeril et al Circulation 1999;99:779

Differences in LDL-C

1. Disease-specificRenalDiabetes

2. Weight lossThousands

3. Lipid managementHundreds

4. SurvivalMediterranianFish

Goals of Diet(s)

Exercise

Exercise

Myers, NEJM 2002;346:793

• 6,213 men• ETT for clinical reasons• 2,534 normal• 3,679 with CAD• Mean f/u 6.2 years• Age 59 + 11•Peak capacity stronger predictor than cigs, HTN, DM, Chol

Effect of Exercise on Lipids

Kokkinos Arch Int Med 1995:155:415

2906 menage 30-64 yearsexercise treadmill test to exhaustionclassified into 6 groups based on

average miles run per week

Effect of Exercise on Lipids

Kokkinos Arch Int Med 1995:155:415

HDL, LDL versus miles per week

40

45

50

55

60

0-2 mi 3-6 mi 7-10 mi 11-14 mi 15-20 mi 21-60 mi

Miles Run per Week

HD

L m

g%

0

20

40

60

80

100

120

140

LD

L m

g%

Y2

HDLLDL

Cholesterol-Lowering Drugs

Prescription Non-Prescription

StatinFibrateNiacinResinsOrlistat

Ezetimibe

Fiber (brans)Garlic

Fish OilPlant sterols (Benecol)

Cholesterol Modifying Agents

4S

Summary of Key End-pointsSummary of Key End-pointsSimvastatin vs. placeboSimvastatin vs. placebo

Total mortalityTotal mortality

CAD mortalityCAD mortality

Major coronary Major coronary eventsevents

PTCA/CABGPTCA/CABG

Event-freeEvent-freesurvivalsurvival

0.20.2 0.40.4 0.60.6 0.80.8 1.01.0 1.21.2

p=0.0003

p<0.00001

p<0.00001

p<0.00001

p<0.00001

Relative risk (95% CI)Relative risk (95% CI)Reduced Increased

Effects of Statin on Total Mortality (4S)Effects of Statin on Total Mortality (4S)Diabetics (n= 201) vs Non-Diabetics (n=4242)Diabetics (n= 201) vs Non-Diabetics (n=4242)

25

1114

8

0

5

10

15

20

25

30

With Diabetes Without Diabetes

% m

ort

alit

y

Placebo Simvastatin

43% risk43% riskreductionreduction

28% risk28% riskreductionreduction

Presented at the ACC Meeting March 19-22, 1995Presented at the ACC Meeting March 19-22, 1995

When should weWhen should we

STARTSTART

therapy?therapy?

When should weWhen should we

STARTSTART

therapy?therapy?

MIRACLMIRACL

P=0.048

Schwartz JAMA 2001;285:1711

CHAMPCHAMP

Fonarow, AJC 2001;87:819

CHAMPCHAMP

Fonarow, AJC 2001;87:819

When should weWhen should we

STARTSTART

therapy?therapy?

When should weWhen should we

STARTSTART

therapy?therapy?

AS SOON AS POSSIBLE!!!!

Why start drugs in the Hospital?Why start drugs in the Hospital?

• Use diet and exercise on all patients, wait 3-6 months for statin therapy:

4% will have LDL < 100 mg/dL

• Start statin in the hospital, recommend diet and exercise:

96% get needed therapy4% "overtreated"

How do you improve your rate of How do you improve your rate of therapy?therapy?

How do you improve your rate of How do you improve your rate of therapy?therapy?

Improving Process of Care

Finding a "Champion"

Develop a team

Baseline measurement

Use the team to develop new processespocket remindersstandard orderscomputer reminders

Follow-up measurement

Clinician ChecklistClinician Checklist

Patient ChecklistPatient Checklist

Discharged on Lipid-lowering Therapy(preliminary data Cardiac Surgery)

38

88

100 10094

0

10

20

30

40

50

60

70

80

90

100

Baseline 8 mos 10 mos 11 mos 14 mos

Per

cen

t

Get With the Guidelines!Get With the Guidelines!

The GuidelinesThe Guidelines

Therapy GoalSmoking Complete cessationBP control 130-140/85-90Cholesterol LDL<100, HDL>35, TG<200Exercise 30 min, 3-4x/weekWeight control BMI 21-25 kg/m2

DM Gluc~100, HbA1c < 7Antiplatelet/warfarin ASA 80-325 mgACE Post-MI, EF<40Beta blockers Post-MI

How often do we provide these therapies?How often do we provide these therapies?

Therapy Rate ReferenceSmoking 48% Doescher J Fam Prac 2000;49;543

BP control 25% Berlowitz, NEJM 1998;339:1957Cholesterol 31.7% Fonarow Circ 2001;103:38

Exercise 19.1% MMWR 1998;47:91

Weight control 10.4% MMWR 1998;47:91DM 45% UKPDS AHJ 1999;138:353

Antiplatelet/warfarin 84% Rogers Circ 1994;90:2103ACE 75% (chf) J Gen Int Med 1997;12:563

Beta blockers 17.4% (iv) Rogers Circ 1994;90:2103PTCA (AMI) 30.3% Rogers Circ 1994;90:2103

State StandingsState Standings

State RankCalifornia 41Oklahoma 42West Virginia 43Alabama 44

Texas 45Illinois 46Georgia 47New Jersey 48Louisiana 49Mississippi 50Arkansas 51Puerto Rico 52

Jencks et al. JAMA 2000;284:1670

State RankNew Hampshire 1

Vermont 2Maine 3

Minnesota 4

Massachusetts 5Connecticut 6

North Dakota 7Iowa 8

Colorado 9Oregon 10

Wisconsin 11

Ranked by CV indicators, mammog, immune, etc

What is the GWTG Plan?

Hospitals Medical Groups

KaiserTenetCHCW

Large payors Government

Educational programs Tools Carrots Sticks

Everything still in development

Management of MedRx

On transfer out of the ICUABC2D

aspirinbeta blockercholesterol agentconverting enzyme inhibitor (ACE)diabetes

On the wardhypertension therapysmoking cessationBMI recommendationsexercise recommendations

"Get with the Guidelines" Outcomes

85 82

67

38

0 0 0 0 0

95.5 9789.6

98.4 100 100 100 100 100

0

10

20

30

40

50

60

70

80

90

100

ASA Beta ACE Chol DM Smoke HTN Exerc BMI

Guideline

Pe

rce

nt

All CABG-only, 10/1/2001 to 12/31/2001compare to 1999 data

CSMC Cardiothoracic Surgery

Effects of Various Cardiac TherapiesEffects of Various Cardiac Therapies

Therapy Survival QOL MI AdmitsRx A 0

Rx B 0

Rx C

Effects of Various Cardiac TherapiesEffects of Various Cardiac Therapies

Therapy Survival QOL MI Admits PTCA (non-MI) 0 CABG (3v, nl EF, CCS I, II) 0 Statin

Effects of Various Cardiac TherapiesEffects of Various Cardiac TherapiesTherapy Survival QOL MI Admits

PTCA (non-MI) 0

CABG (3v, nl EF, CCS I, II) 0

Exercise

Weight control

Smoking cessation

HTN control

Diabetes control

ASA / coumadin

ACE

Cholesterol lowering

Beta blocker

Why should you do this? JCAHO Oryx HEDIS Marketing I swear by Apollo the physician, by Aesculapius, Hygeia, and Panacea, and take to witness all the gods, all the goddesses to keep according to my ability and my judgement the following oath: ...

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