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AHA Secondary Prevention Guidelines
““Get with the Guidelines”Get with the Guidelines”And MOREAnd MORE……
Timothy A. Denton, M.D., F.A.C.C.High Desert Heart Institute
Victorville, CA
AHA/ACC Scientific Statement
AHA/ACC Guidelines for Secondary Prevention in Patients with Coronary and Other Vascular
Disease: 2001 Update
Sidney C Smith, Steven N Blair, Robert O Bonow,Lawrence M Brass, Manuel D Cerqueira, Kathleen Dracup,
Valentin Fuster, Antonio Gotto, Scott M Grundy,Nancy Houston Miller, Alice Jacobs, Daniel Jones,
Ronald M Krauss, Lori Mosca, Ira Ockene,Richard C Pasternack, Thomas Pearson, Marc A Pfeffer,
Rodman D Starke, Kathryn A Taubert
Circulation 2001;104:1577-1579
www.americanheart.orgwww.americanheart.orgwww.acc.orgwww.acc.org
To Which Patients dothe Guidelines apply?
• Coronary artery disease• Carotid disease• Peripheral vascular disease• Abdominal aortic aneurysm• Diabetics
ABC2
The Guidelines Therapy Goal A Antiplatelet/warfarin ASA 81-325 mg B Beta blockers Post-MI, All C Cholesterol LDL<100 C ACE Post-MI, EF<40, All D DM Gluc~100, HbA1c < 7 C Smoking Complete cessation E Exercise 30 min, 3-4x/week W Weight control BMI 18.5-25 kg/m2 H BP control 130-140/80-90
DM Cigs Exercise BMI HTN
Antiplatelet / anticoagulant therapy• Intervention recommendations:
–Start and continue indefinitely aspirin 75–325 mg/d if not contraindicated.–Consider clopidogrel 75 mg/d or warfarin if aspirin contraindicated.–Manage warfarin to INR=2.0 to 3.0 in post-MI patients when clinically indicated or for those unable to
take aspirin or clopidogrel.
AHA Secondary Prevention Guidelines2001
GWTG and MORE…
What is the correct dose of aspirin?
• Acute MI – 162-325 mg
• Secondary prevention – 75-162 mg
• AHA/ACC MI GuidelinesCirculation 2004;110:588
GWTG and MORE…
How long should we give clopidogrel?
Addition of clopidogrel to ASA (75-325) after ACSreduces death+MI+CVA at 1 year
(curves continue to diverge, CURE trial)
Circulation 2004;110 – to be published
GWTG and MORE…
What about warfarin?
• Meta-analysis: ASA + warfarin in ACS 29-45% reduction in mortalityJ Inv Cardiol 2004;16:271
• RCT: warfarin+ASA vs ASA post MI29% reduction in death+MI+CVANEJM 2002;347:969
Beta blockers
• Start in all patients post MI and post ACS
• Continue indefinitely
• Observe usual contraindications.
• Use as needed to manage CHF, angina, rhythm, or blood pressure in all other patients.
AHA Secondary Prevention Guidelines2001
GWTG and MORE…How aggressive can we be with beta blockers?
Using CARDIOSELECTIVE beta-blockersThere was no change in FEV1 or COPD exacerbations (up to 12 weeks).
Atenolol, bisoprolol, metoprololblock β1 > β2 20:1
Salpeter et al. Ann Int Med 2002;137:715
“…unfounded fears…”
ACE inhibitors• Treat all patients indefinitely post MI
• Consider use in all patients with coronary or other vascular disease
• Early use in anterior MI, previous MI, Killip Class II (S3 gallop, rales, radiographic CHF)
AHA Secondary Prevention Guidelines2001
Benefits in HOPE• 9,541 subjects randomized to ramipril 10 mg/day or placebo
and vitamin E 400 Units/day or placebo for 5 years• Terminated early at 4.5 years• All patient subgroups had benefit with ACEI.• Primary endpoint (MI, stroke, or death from cardiovascular
causes) was significantly reduced by 22% with ramipril.• Risk reduction with ramipril was evident at 1 year and
statistically significant at 2 years.• Vitamin E arm showed no benefit.
HOPE Study Investigators. HOPE Study Investigators. N Engl J MedN Engl J Med 2000;342:145–160. 2000;342:145–160.
GWTG and MORE…
ACE and ARB
More data on ARBsprimary HTNNo “HOPE” equivalent, yetCHF if reaction to ACESome CHF data coming out now
Can you identify these?
Lipid management• LDL-cholesterol goal < 100 mg/dl • Statins as first line therapy for LDL lowering • If LDL low but HDL < 40 mg/dl, consider fibrate or niacin as first line therapy (especially in diabetes) • If TG’s are high, do not use a resin
• TG 200-499, use fibrate/niacin after statins• TG >500, use fibrate/niacin before statins• Omega-3 FA’s for high TG’s
AHA Secondary Prevention Guidelines2001
REVERSAL
P=0.02Nissen JAMA 2004;291:1071
Reversal of Atherosclerosis with Aggressive Lipid Lowering
•DB Random atorv v. prava (79 v. 110)•IV US•Atheroma vol
-0.4
2.7
-1
-0.5
0
0.5
1
1.5
2
2.5
3
Atorv Prava
Per
cen
t C
ha
ng
e
ASCOTT-LLA
P=0.0005
Nissen JAMA 2004;291:1071
Anglo-Scandinavian Cardiac Outcomes Trial – Lipid Lowering Arm
• 19,342 HTN + 3 RF• Tchol < 250• Atorva v placebo• trial stopped 3.3 yrs
100 89
389
178 185154
121
486
247212
0
100
200
300
400
500
600
All Events CVA AllCV All Cor Death
Percen
t C
ha
ng
e
P=0.024
P=0.0005
P=0.0005 P=0.16
ACCESS
Smith Phamacoeconomics 2003;21:13
Atorvastatin Comparative Cholesterol Efficacy and Safety Study
• 3,387• 54 weeks• Atorva, fluva, lova, prava, simva• titrate to LDL < 100
Drug Total Cost to Goal
Atorva 683.37
fluva +211.35
lova +607.96
Prava +424.60
simva +95.74
HPS—Simvastatin: Vascular Events by Baseline LDL-C
358 (21.0%)282 (16.4%)<100
871 (24.7%)668 (18.9%)100–129
2585 (25.2%)2033 (19.8%)All patients
1356 (26.9%)1083 (21.6%)130
Placebo (n=10,267)
Statin (n=10,269)
Baseline LDL-C (mg/dL)
Event rate ratio (95% CI)Event rate ratio (95% CI)Statin betterStatin better Statin worseStatin worse
0.40.4 0.60.6 0.80.8 1.01.0 1.21.2 1.41.4
www.hpsinfo.orgwww.hpsinfo.org
0.76 (0.720.76 (0.72–0.81)–0.81)p<0.0001p<0.0001
CARDS
Colhoun et al. Lancet 2004;364:685-696
Collaborative Atorvastatin Diabetes Study
• 2,838 diabetics, no prior CV disease• atorvastatin 10 mg vs placebo• 3.9 years, terminated 2 years early
-37 -36-31
-48
-60
-50
-40
-30
-20
-10
0
One Event ACS Revasc CVA
Rat
e R
educ
tion
(%
)
GWTG and MORE…It’s not 100 anymore, it’s 70!
Grundy et al. Circulation 2004;110:227
• Known CAD or DM “optional”LDL goal of <70 mg/dl
• Based on new trialsHPSALLHATPROVE-ITASCOT-LLAPROSPER
• Two trials to comeSEARCHTNT
Diabetes
• Measure Hgb A1c
• Appropriate hypoglycemic therapy to
achieve near-normal plasma glucose as
determined by Hgb A1c < 7.0
• Treatment of other risks
(weight, activity, BP, lipids)
AHA Secondary Prevention Guidelines2001
ADA Standards of Medical Care for Patients with Diabetes
• Glycemic control: HbA1C <7%
• Blood pressure control: <130/80 mm Hg
• Target lipid levels: LDL-C <100 mg/dL HDL-C >45 mg/dL in men, >55 mg/dL in
women TG <150 mg/dL
• Smoking cessation
ADA. ADA. Diabetes CareDiabetes Care 2002;25:S33 2002;25:S33––S49.S49.
But…tight glycemic control has little effect on survival
You get more SURVIVAL benefit in diabetics if you start:
A Statin
An ACE inhibitor
ADA. ADA. Diabetes CareDiabetes Care 2002;25:S33 2002;25:S33––S49.S49.
Smoking• Goal is complete cessation• Avoid second hand smoke• Provide:
• counseling• tobacco cessation programs• pharmacologic therapy including
nicotine replacement and buproprion
AHA Secondary Prevention Guidelines2001
Doll et al. BMJ 1994;309:901-911
Survival Effects of Cigarette Smoking
Overall SurvivalAll levels of smoking
Physical activity• GOAL
Minimum: 30 minutes 3–4 days/week Optimal: daily
• Intervention recommendations: Assess risk, preferably with exercise test, to guide prescription. Encourage minimum of 30–60 minutes of activity (walking, jogging, cycling, or other aerobic activity),
preferably daily or at least 3–4 times weekly. Supplement with increased daily lifestyle activities (walking breaks at work, gardening, household work). Advise medically supervised programs for moderate- to high-risk patients.
AHA Secondary Prevention Guidelines2001
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
The more you walk
the longer you’ll live…
GWTG and MORE…
AHA Secondary Prevention GuidelinesWeight Management
• Goal: BMI 18.5–24.9 kg/m2
• Intervention recommendations: Calculate BMI and measure waist circumference
as part of evaluation. Start weight management and physical activity as
appropriate. Monitor response of BMI and waist circumference
to therapy. If BMI 25 kg/m2, goal for waist circumference is
40 inches in men, 35 inches in women.
Smith SC Jr et al. Smith SC Jr et al. CirculationCirculation 2001;104:1577-1579. 2001;104:1577-1579.
BMI and All-Cause Mortality
Calle, NEJM 1999;341:1097
Blood pressure• General goal: BP < 140/90• Diabetes: BP < 130/80 (ADA)• Renal failure/heart failure:
BP < 130/85 (JNC6)• Lifestyle modification• Dietary management
• restrict salt intake• fresh fruits and vegetables
AHA Secondary Prevention Guidelines2001
HOT Trial
Lancet 1998;351(9118):1755-62
Diastolic blood pressure Systolic blood pressure
70 75 80 85 90 95 100 105 120 130 140 150 160 170 180 190
Hormone replacement therapy
• Do not start HRT for secondary prevention
AHA Secondary Prevention Guidelines2001
Circulation 2001;104:499www.americanheart.org
GWTG and MORE…
L-Arginine
C
C
H
NH
H
HH
C HH
C HH
N H
CN HNH
H
C O
O
H
GWTG and MORE…
L-Arginine• Increases nitric oxide levels• Doses 1-9 grams per day• Improves endothelial function• Restores ASA-induced dysfunction• Antioxidant• Improves renal function•Improves claudication
increases walking distance by 155%JACC 1998;32:1336
GWTG and MORE…
www.srmjol.is
GWTG and MORE…Fish Oil
www.srmjol.is
Blue Whiting CapelinHerring
C = 8 - 24
Fatty Acids
Lipids
HO
O
Triglycerides
O
O
O
O
O
O
Phospholipids
O
O
O
O
O
PGO
O
PUFA (polyunsaturated fatty acid) Nomenclature
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Common name - -Linoleic acidSystematic name - all cis-9,12-octadecadienoic acidSystematic name - cis-9, cis-12-octadecadienoic acidChemist’s name - 18:2 (9Z, 12Z) (Z=cis, E=trans)Chemist’s name - 18:2 9,12 (assume cis, indicate trans)Nutritionist’s name #1 - 18:2 (n-6)Nutritionist’s name #2 - 18:2 -6
HO
O
18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1
Fish Oil
• 9 patients• 6 weeks
1 g/d N-3 PUFA1 U tocopherol/d
• 6 weeks5 g/d fish oil
• Slower VLDL and LDL oxidation
Hau et al. Arterio Thromb Vasc Biol 1996;16:1197
-54 -56
-40
23
-60
-50
-40
-30
-20
-10
0
10
20
30
TG VLDL TG VLDL-C LDL
Fish Oil vs Gemfibrozil
29.7
11.0
-37.1
33.6
17.1
-40.4
-50
-40
-30
-20
-10
0
10
20
30
40
LDL HDL TG
FO Gemfib
Gemfibrozil 1,200 mg/dFish oil 4g/day
Stalenhoef et al Atherosclerosis 2000;153:129
n-3 PUFA’s and SCD
Albert et al NEJM 2002;346:1113
GISSI-Prevenzione
GISSI group, Lancet 1999;354:447
GWTG and MORE…
Fish Oil
GWTG and MORE…
Fish Oil
GWTG and MORE…
Fish Oil
EPA + DHA
Mediterranean 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
Underlying Cause
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
The Guidelines Therapy GWTG Goal A Antiplatelet/warfarin Start the Rx B Beta blockers Start the Rx C Cholesterol Start the Rx C ACE Start the Rx D DM Start the Rx C Smoking Counseling E Exercise Counseling W Weight control Counseling H BP control 130-140/80-90
ABC2 DM Cigs Exercise BMI HTN
…and MORE
• Long-term – lower ASA dose• Clopidogrel benefits out to 1 year• More use of warfarin in CAD• More aggressive use of Beta blockers• Lower LDL levels• L-arginine• Fish oil• Mediterranean diet
The END