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

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0

0.5

1

1.5

2

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3

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Per

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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

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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

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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