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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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