1 Οδηγίες AHA/ACC για δευτερογενή πρόληψη για ασθενείς με...

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Οδηγίες Οδηγίες AHA/ACC AHA/ACC για δευτερογενή για δευτερογενή πρόληψη πρόληψη για ασθενείς με καρδιαγγειακή για ασθενείς με καρδιαγγειακή

αθηροσκληρωτική νόσοαθηροσκληρωτική νόσο: : Αναθεώρηση Αναθεώρηση 2006 2006

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Το πλήρες κείμενο των οδηγιών μπορείτε να το βρείτε στο δικτυακό τόπο της AHA (www.americanheart.org) και του ACC (www.acc.org)

Circulation 2006;113:2363-2372 and J Am Coll Cardiol 2006;47:2130-2139

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IntroductionIntroduction• Since the 2001 update of the AHA/ACC consensus statement on secondary prevention, important evidence from clinical trials has emerged that further supports and broadens the merits of aggressive risk reduction therapies

• This growing body of evidence confirms that aggressive comprehensive risk factor management improves survival, reduces recurrent events and the need for interventional procedures, and improves the quality of life

• The secondary prevention patient population includes those with established coronary and other atherosclerotic vascular disease, including peripheral arterial disease, atherosclerotic aortic disease and carotid artery disease.

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AHA/ACC Secondary Prevention for Patients AHA/ACC Secondary Prevention for Patients with Coronary Artery and Other Atherosclerotic with Coronary Artery and Other Atherosclerotic

Vascular DiseaseVascular Disease

*Dr. Pasternak withdrew from the Writing Group on June 22nd, 2004, when he accepted an offer of employment as Vice President, Clinical Research, Cardiovascular and Atherosclerosis at Merck Research Laboratories.


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Class I

Benefit >>> Risk

Procedure or treatment SHOULD

be performed or administered

Class IIa

Benefit >> RiskAdditional studies

with focused objectives needed

IT IS REASONABLE to perform

procedure or administer treatment

Class IIb

Benefit ≥ RiskAdditional studies

with broad objectives needed; Additional registry

data would be helpful

Procedure or treatment MAY BE

CONSIDERED

Class III

Risk ≥ BenefitNo additional studies

needed

Procedure or treatment should

NOT be performed or administered SINCE IT IS NOT HELPFUL

AND MAY BE HARMFUL

Applying Classification of Recommendations Applying Classification of Recommendations and Level of Evidenceand Level of Evidence

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Level A

Multiple (3-5) population risk strata evaluated

General consistency of direction and magnitude of

effect

Class I

Recommendation that procedure or treatment is

useful/ effective

Sufficient evidence from

multiple randomized

trials or meta-analyses

Class IIa

Recommendation in favor of

treatment or procedure being useful/ effective

Some conflicting evidence from

multiple randomized


Class IIb

Recommendation’s usefulness/ efficacy less

well established

Greater conflicting

evidence from multiple

randomized trials or meta-

analyses

Class III

Recommendation that procedure

or treatment not useful/ effective

and may be harmful

Sufficient evidence from

multiple randomized


Applying Classification of Recommendations Applying Classification of Recommendations and Level of Evidenceand Level of Evidence

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Level B

Limited (2-3) population risk strata evaluated

Class I

Recommen-dation that

procedure or treatment is

useful/ effective

Limited evidence from single randomized trial or non-randomized

studies

Class IIa

Recommen-dation in favor of

treatment or procedure being useful/ effective

Some conflicting evidence from

single randomized trial

or non-randomized

studies

Class IIb

Recommen-dation’s

usefulness/ efficacy less well

established

Greater conflicting evidence from

single randomized trial

or non-randomized

studies

Class III

Recommen-dation that procedure or

treatment not useful/effective

and may be harmful

Limited evidence

from single randomized trial

or non-randomized

studies

Applying Classification of Recommendations Applying Classification of Recommendations and Level of Evidence and Level of Evidence

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Applying Classification of Recommendations Applying Classification of Recommendations and Level of Evidence and Level of Evidence

Level C

Very limited (1-2) population risk strata evaluated

Class I

Recommen-dation that

procedure or treatment is

useful/ effective

Only expert opinion, case

studies, or standard-of-

care

Class IIa

Recommendation in favor of

treatment or procedure being useful/effective

Only diverging expert opinion, case studies, or standard-of-care

Class IIb

Recommen-dation’s

usefulness/ efficacy less well

established

Only diverging expert opinion, case studies, or standard-of-care

Class III

Recommendation that procedure or

treatment not useful/effective

and may be harmful

Only expert opinion, case

studies, or standard-of-care

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Secondary Prevention DefinitionSecondary Prevention Definition

• Therapy to reduce recurrent cardiovascular events and decrease cardiovascular mortality in patients with established atherosclerotic vascular disease

• Patients covered include those with established coronary and other atherosclerotic vascular disease, including peripheral arterial disease, atherosclerotic aortic disease and carotid artery disease

• Individuals with sub-clinical atherosclerosis and patients whose only manifestation is diabetes are covered in other guidelines

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Components of Secondary Components of Secondary PreventionPrevention

Cigarette smoking cessationCigarette smoking cessationBlood pressure controlBlood pressure controlLipid management to goalLipid management to goalPhysical activityPhysical activityWeight management to goalWeight management to goalDiabetes management to goalDiabetes management to goal

Antiplatelet agents / anticoagulantsAntiplatelet agents / anticoagulants

Renin angiotensin aldosterone system blockersRenin angiotensin aldosterone system blockers

Beta blockersBeta blockers

Influenza vaccinationInfluenza vaccination

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Evidence Based TherapiesEvidence Based Therapies

The writing group emphasizes the importance of giving consideration to the use of cardiovascular medications that have been proven to be of benefit in randomized clinical trials.

This approach strengthens the evidence-based foundation for therapeutic application of these guidelines.

The committee acknowledges that in many trials there isunder-representation of ethnic minorities, women, and the elderly.

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Goal: Complete Cessation and No Exposure to Environmental Tobacco Smoke

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

Cigarette Smoking RecommendationsCigarette Smoking Recommendations

•Ask about tobacco use status at every visit.

•Advise every tobacco user to quit.

•Assess the tobacco user’s willingness to quit.

•Assist by counseling and developing a plan for quitting.

•Arrange follow-up, referral to special programs, or pharmacotherapy (including nicotine replacement and bupropion.

•Urge avoidance of exposure to environmental tobacco smoke at work and home.

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0.1 1.0 10Ceased smoking Continued smoking

RR (95% Cl)Study

Aberg, et al. 1983 0.67 (0.53-0.84)

Herlitz, et al. 1995 0.99 (0.42-2.33)

Johansson, et al. 1985 0.79 (0.46-1.37)

Perkins, et al. 1985 3.87 (0.81-18.37)

Sato, et al. 1992 0.10 (0.00-1.95)

Sparrow, et al. 1978 0.76 (0.37-1.58)

Vlietstra, et al. 1986 0.63 (0.51-0.78)

Voors, et al. 1996 0.54 (0.29-1.01)

Cigarette Smoking Cessation: Risk of Non-fatal MI*Cigarette Smoking Cessation: Risk of Non-fatal MI*

Critchley JA et al. JAMA. 2003;290:86-97.*Includes those with known coronary heart disease

CI=Confidence interval, RR=Relative risk

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Ask and document pt’stobacco use status

Advise: Provide a strong, personalizedmessage to quit using tobacco

Assess* readiness to quit in next 30 days

Prevent Relapse• Congratulate successes• Encourage to remain tobacco-free• Discuss benefits experienced by patient• Address weight gain, negative mood, and lack of support

Increase Motivation• Relevance to patients personal situation• Risks: short and long term, environmental• Rewards: potential benefits of quitting• Roadblocks: identify barriers and potential solutions• Repetition: repeat motivational intervention• Reassess readiness to quit

Assist • Negotiate a plan • STAR**• Discuss pharmacotherapy• Social support• Provide educational materials

Arrange follow-up to check plan or adjust meds• Call right before and after quit date• Weekly follow-up x 2 weeks, then monthly x 6 months• Ask about difficulties (withdrawal, depressed mood)• Build upon successes• Seek commitment to stay tobacco-free

**STARSet quit dateTell family, friends, and coworkers about itAnticipate challenges: withdrawal, breaksRemove tobacco from the house, car, and social life

Recent Quitter(<6 months) Current User

Not Ready Ready

Smoking Cessation AlgorithmSmoking Cessation Algorithm

Treating Tobacco Use and Dependence: A Clinical Practice Guideline, U.S. Department of Health and Human Services, June 2000

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Smoking Cessation Pharmacotherapy*Smoking Cessation Pharmacotherapy*

Agent Caution Side Effects

Dosage Duration Instructions

Bupropion SR(Zyban®)

Seizure disorderEating disorder

Taking MAO inhibitor

Pregnancy

InsomniaDry mouth

150 mg QAMthen

150 mg BID

3 days

Maintenance (8 weeks, but may be used

up to 6 months)

Start 1-2 weeks before quit date.

Take second dose in early afternoon or decrease to 150

mg QAM for insomnia.

TransdermalNicotinePatch**

Within 2 weeks of a MI

Unstable anginaArrhythmias

Decompensated heart failure

Skin reactionInsomnia

21 mg QAM14 mg QAM 7 mg QAM

or15 mg QAM

4 weeks2 weeks2 weeks

8 weeks

Apply to different hairless site daily.

Remove before bed for insomnia.Start at <15 mg for

<10 cigs/day

*Pharmacotherapy combined with behavioral support provides the best success rate**Other nicotine replacement therapy options include: nicotine gum, lozenge, inhaler, nasal spray

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Goal: <140/90 mm Hg or <130/80 if diabetes or chronic kidney disease


Blood Pressure Control RecommendationsBlood Pressure Control Recommendations

Blood pressure 120/80 mm Hg or greater:

Initiate or maintain lifestyle modification: weight control, increased physical activity, alcohol moderation, sodium reduction, and increased consumption of fresh fruits vegetables and low fat dairy products

Blood pressure 140/90 mm Hg or greater (or 130/80 or greater for chronic kidney disease or diabetes)

As tolerated, add blood pressure medication, treating initially with beta blockers and/or ACE inhibitors with addition of other drugs such as thiazides as needed to achieve goal blood pressure


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Prospective Studies Collaboration. Lancet. 2002;360:1903-1913

Usual Diastolic BP (mm Hg)Usual Systolic BP (mm Hg)

Isch

emic

Hea

rt D

isea

se M

ort

alit

y

50-59

60-69

70-79

80-89Age at Risk (Y)

40-49

256

128

64

32

16

8

4

2

1

0120 140 160 180

50-59

60-69

70-79

80-89

Age at Risk (Y)

40-49

256

128

64

32

16

8

4

2

1

080 90 100 11070

Blood Pressure: Lower is BetterBlood Pressure: Lower is Better

Isch

emic

Hea

rt D

isea

se M

ort

alit

y

Ischemic Heart Disease Mortality

BP=Blood pressure

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Veterans Administration, 1967

Veterans Administration, 1970

Hypertension Stroke Study, 1974

USPHS Study, 1977

EWPHE Study, 1985

Coope and Warrender, 1986

SHEP Study, 1991

STOP-Hypertension Study, 1991

MRC Study, 1992

Syst-Eur Study, 1997

Total 0 0.5 1.0 1.5 2.0

0.79 (0.69 to 0.90)

He J et al. Am Heart J 1999; 138:211-219

Better than placebo Worse than placebo

Blood Pressure: Risk of CHD with Active TreatmentBlood Pressure: Risk of CHD with Active Treatment

CHD=Coronary heart disease

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Yes >100 >160 Stage 2 Hypertension

Yes 90–99 140–159 Stage 1 Hypertension

Yes 80–89 120–139 Pre-hypertension

Encourage <80 <120 Normal

With compelling indications

Initial drug therapy Lifestyle

modificationDBP* mmHg

SBP* mmHg

BP classification

JNC VII Guidelines for Management and TreatmentJNC VII Guidelines for Management and Treatment

ACEI=Angiotensin converting enzyme inhibitor, ARB=Angiotensin receptor blocker, BB=-blocker, BP=Blood pressure, CCB=Calcium channel blocker, DBP=Diastolic blood pressure, SBP=Systolic blood pressure

Chobanian AV et al. JAMA. 2003;289:2560-2572

*Treatment determined by highest blood pressure category. †Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension.‡Treat patients with chronic kidney disease or diabetes mellitus to blood pressure goal of <130/80 mmHg.

Drug(s) for the compelling indications.‡

Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed.

Drug(s) for compelling indications. ‡

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Modification Recommendation Approximate SBP Reduction Range

Weight reduction Maintain normal body weight (BMI=18.5-24.9)

5-20 mmHg/10 kg weight lost

Adopt DASH eating plan

Diet rich in fruits, vegetables, low fat dairy and reduced in fat

8-14 mmHg

Restrict sodium intake

<2.4 grams of sodium per day 2-8 mmHg

Physical activity Regular aerobic exercise for at least 30 minutes on most days of the week

4-9 mmHg

Moderate alcohol consumption

<2 drinks/day for men and <1 drink/day for women

2-4 mmHg

JNC VII Lifestyle Modifications for BP ControlJNC VII Lifestyle Modifications for BP Control


BMI=Body mass index, SBP=Systolic blood pressure

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Clinical-Trial BasisCompelling Indication

ALLHAT, HOPE, ANBP2,LIFE, CONVINCE

High CAD Risk

ACC/AHA Post-MI Guideline, BHAT, SAVE, Capricorn, EPHESUS

Post-MI

MERIT-HF, COPERNICUS, CIBIS, SOLVD, AIRE, TRACE, Val-HeFT,

RALES

Initial Therapy Options

Diuretic, BB, ACEI, CCB

BB, ACEI, Aldo Ant

Diuretic, BB, ACEI,ARB, Aldo Ant

Heart Failure

JNC VII Compelling Indications for Drug ClassesJNC VII Compelling Indications for Drug Classes

ACEI=Angiotensin converting enzyme inhibitor, Aldo Ant=Aldosterone antagonist, ARB=Angiotensin receptor blocker, BB=b-blocker, CAD=Coronary artery disease, CCB=Calcium channel blocker, MI=Myocardial Infarction


Recurrent Stroke Prevention PROGRESSDiuretic, ACEI

NKF-ADA Guideline,UKPDS, ALLHAT

NKF Guideline, Captopril Trial, RENAAL, IDNT, REIN, AASK

Diuretic, BB, ACEI,ARB, CCB

ACEI, ARB

Diabetes Mellitus

Chronic Kidney Disease

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Lipid Management GoalLipid Management Goal

LDL-C should be less than 100 mg/dL

Further reduction to LDL-C to < 70 mg/dL is reasonable


*Non-HDL-C = total cholesterol minus HDL-C


If TG >200 mg/dL, non-HDL-C should be < 130 mg/dL*

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Risk Category LDL-C and non-HDL-C Goal

Initiate TLCConsider

Drug Therapy

High risk: CHD or CHD risk equivalents (10-year risk >20%)and

<100 mg/dL if TG > 200 mg/dL,

non-HDL-C should be < 130 mg/dL

100 mg/dL >100 mg/dL (<100 mg/dL: consider drug

options)

Very high risk:ACS or established CHDplus: multiple major risk factors (especially diabetes) or severe and poorly controlled risk factors

<70 mg/dL, non-HDL-C < 100

mg/dL

All patients >100 mg/dL (<100 mg/dL: consider drug

options)

Grundy, S. et al. Circulation 2004;110:227-39.

Lipid Management Goals: NCEPLipid Management Goals: NCEP

ATP=Adult Treatment Panel, CHD=Coronary heart disease, LDL-C=Low-density lipoprotein cholesterol, TLC=Therapeutic lifestyle changes

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Lipid Management RecommendationsLipid Management Recommendations

Start dietary therapy (<7% of total calories as saturated fat and <200 mg/d cholesterol)

Adding plant stanol/sterols (2 gm/day) and viscous fiber (>10 mg/day) will further lower LDL

Promote daily physical activity and weight management.

Encourage increased consumption of omega-3 fatty acids in fish or 1 g/day omega-3 fatty acids in capsule form for risk reduction.




For all patients

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*Trans fatty acids also raise LDL-C and should be kept at a low intake.Note: Regarding total calories, balance energy intake and expenditure to maintain desirable body weight.

<200 mg/dCholesterol

~15% of total caloriesProtein

20–30 g/dFiber

50%–60% of total caloriesCarbohydrate (esp. complex carbs)

25%–35% of total caloriesTotal fat

Up to 20% of total caloriesMonounsaturated fat

Up to 10% of total caloriesPolyunsaturated fat

<7% of total caloriesSaturated fat*

Recommended IntakeNutrient

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

ATP III Dietary RecommendationsATP III Dietary Recommendations

ATP=Adult Treatment Panel

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If baseline LDL-C > 100 mg/dL, initiate LDL-lowering drug therapy

If on-treatment LDL-C > 100 mg/dL, intensify LDL-lowering drug therapy (may require LDL lowering drug combination)

If baseline is LDL-C 70 to 100 mg/dL, it is reasonable to treat to LDL < 70 mg/dL

Assess fasting lipid profile in all patients, and within 24 hours of hospitalization for those with an acute event. For patients hospitalized, initiate lipid-lowering medication as recommended below prior to discharge according to the following schedule:



When LDL lowering medications are used, obtain at least a 30-40% reduction in LDL-C levels.


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If TG are 200-499 mg/dL, non-HDL-C should be < 130 mg/dL

Further reduction of non-HDL to < 100 mg/dL is reasonable

Therapeutic options to reduce non-HDL-C: More intense LDL-C lowering therapy I (B) orNiacin (after LDL-C lowering therapy) IIa (B) orFibrate (after LDL-C lowering therapy) IIa (B)

If TG are > 500 mg/dL, therapeutic options to prevent pancreatitis are fibrate or niacin before LDL lowering therapy; and treat LDL-C to goal after TG-lowering therapy. Achieve non-HDL-C < 130 mg/dL, if possible




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Baseline Baseline LDL-C (mg/dL)LDL-C (mg/dL)

Statin Statin (n = 10,269)(n = 10,269)

Placebo Placebo (n = 10,267)(n = 10,267)

<100<100 282 (16.4%)282 (16.4%) 358 (21.0%)358 (21.0%)

100–129100–129 668 (18.9%)668 (18.9%) 871 (24.7%)871 (24.7%)

130130 1083 (21.6%)1083 (21.6%) 1356 (26.9%)1356 (26.9%)

All patientsAll patients 2033 (19.8%)2033 (19.8%) 2585 (25.2%)2585 (25.2%)

Event Rate Ratio (95% CI)

Statin Better Statin Worse

0.4 0.6 0.8 1.0 1.2 1.4

0.76 (0.72–0.81)P<0.0001

Heart Protection Study (HPS)

HMG-CoA Reductase Inhibitor: Secondary PreventionHMG-CoA Reductase Inhibitor: Secondary Prevention

20,536 patients with CAD, other occlusive arterial disease, or DM 20,536 patients with CAD, other occlusive arterial disease, or DM randomized to simvastatin (40 mg) or placebo for 5.5 yearsrandomized to simvastatin (40 mg) or placebo for 5.5 years

CAD=Coronary artery disease, CI=Confidence interval, DM=Diabetes mellitus,

HPS Collaborative Group. Lancet 2002;360:7-22

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Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT)—TIMI 22 Study

3 6 9 12 15 18 21 24 27 30

Follow-up (months)

30

25

20

15

10

5

0

P =0.005

Rec

urre

nt M

I or

Car

diac

Dea

th

16% RRRAtorvastatin

Pravastatin

ACS=Acute coronary syndrome, CV=Cardiovascular, MI=Myocardial infarction, RRR=Relative risk reduction

Cannon CP et al. NEJM 2004;350:1495-1504

HMG-CoA Reductase Inhibitor: Secondary HMG-CoA Reductase Inhibitor: Secondary PreventionPrevention

4,162 patients with an ACS randomized to atorvastatin (80 mg) or pravastatin (40 mg) for 24 months

30LaRosa JC et al. NEJM. 2005;352:1425-1435

LDL-C=Low density lipoprotein cholesterol; TNT=Treating to New Targets; HPS=Heart Protection Study; CARE=Cholesterol and Recurrent Events Trial; LIPID=Long-term Intervention with Pravastatin in Ischaemic Disease; 4S=Scandinavian Simvastatin Survival Study.

30

25

20

15

10

5

00 70 90 110 130 150 170 190 210

LDL-C (mg/dL)

TNT (atorvastatin 80 mg/d)

TNT (atorvastatin 10 mg/d)HPS

CARE

LIPIDLIPID

CAREHPS

Eve

nt (

%) 4S

4SStatinPlacebo

Relationship between LDL Levels and Event Rates in Secondary Prevention Trials of Patients with Stable CHD

HMG-CoA Reductase Inhibitor: Secondary HMG-CoA Reductase Inhibitor: Secondary PreventionPrevention

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HDL-C=High-density lipoprotein cholesterol, LDL-C=Low-density lipoprotein cholesterol, TC=Total cholesterol, TG=Triglycerides *Daily dose of 40mg of each drug, excluding rosuvastatin.

Therapy TC LDL HDL TG Patient tolerability

Statins* 19-37% 25-50% 4-12% 14-29% Good

Ezetimibe 13% 18% 1% 9% Good

Bile acid sequestrants 7-10% 10-18% 3% Neutral or

Poor

Nicotinic acid 10-20% 10-20% 14-35% 30-70% Reasonable to Poor

Fibrates 19% 4-21% 11-13% 30% Good

Lipid Management PharmacotherapyLipid Management Pharmacotherapy

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Physical Activity RecommendationsPhysical Activity Recommendations

Assess risk with a physical activity history and/or an exercise test, to guide prescription

Encourage 30 to 60 minutes of moderate intensity aerobic activity such as brisk walking, on most, preferably all, days of the week, supplemented by an increase in daily lifestyle activities

Advise medically supervised programs for high-risk patients (e.g. recent acute coronary syndrome or revascularization, HF)


Goal: 30 minutes 7 days/week, minimum 5 days/week



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Observational study of self-reported physical activity in 772 men with Observational study of self-reported physical activity in 772 men with established coronary heart disease established coronary heart disease

Light or moderate exercise is associated with lower riskLight or moderate exercise is associated with lower risk

Wannamethee SG et al. Circulation 2000;102:1358-1363

Exercise Evidence: Mortality RiskExercise Evidence: Mortality Risk

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Weight Management RecommendationsWeight Management Recommendations


Goal: BMI 18.5 to 24.9 kg/m2Waist Circumference: Men: < 40 inches Women: < 35 inches


Assess BMI and/or waist circumference on each visit and consistently encourage weight maintenance/ reduction through an appropriate balance of physical activity, caloric intake, and formal behavioral programs when indicated.

If waist circumference (measured at the iliac crest) >35 inches in women and >40 inches in men initiate lifestyle changes and consider treatment strategies for metabolic syndrome as indicated.

The initial goal of weight loss therapy should be to reduce body weight by approximately 10 percent from baseline. With success, further weight loss can be attempted if indicated.

*BMI is calculated as the weight in kilograms divided by the body surface area in meters2. Overweight state is defined by BMI=25-30 kg/m2. Obesity is defined by a BMI >30 kg/m2.


35

Mhurchu N et al. Int J Epidemiol 2004;33:751-758

0.5

1.0

2.0

4.0

16 20 24 28 32 36

Body Mass Index (kg/m2)*

Haz

ard

Rat

io

0.5

1.0

2.0

4.0

16 20 24 28 32 36

0.5

1.0

2.0

4.0

16 20 24 28 32 36

HemorrhagicStroke

IschemicStroke

Ischemic HeartDisease

CV Risk Increases with Body Mass IndexCV Risk Increases with Body Mass Index

CV=Cardiovascular

Body mass index is calculated as the weight in kilograms divided by the body surface area in meters2.

36Grundy, et al. Diagnosis and management of the metabolic syndrome: an AHA/NHLBI Scientific Statement.

Circulation 2005;112:2735-2752.

Risk Factor Defining Level

Waist circumference (abdominal obesity) >40 in (>102 cm) in men

>35 in (>88 cm) in women

Triglyceride level >150 mg/dl

HDL-C level <40 mg/dl in men

<50 mg/dl in women

Blood pressure >130/>85 mmHg

Fasting glucose >100 mg/dl

Definition of the Metabolic SyndromeDefinition of the Metabolic SyndromeDefined by presence of >3 risk factors

HDL-C=High-density lipoprotein cholesterol

37

3,234 patients with elevated fasting and post-load glucose levels randomized to 3,234 patients with elevated fasting and post-load glucose levels randomized to placebo, metformin (850 mg twice daily), or lifestyle modification* for 2.8 yearsplacebo, metformin (850 mg twice daily), or lifestyle modification* for 2.8 years

Lifestyle modification reduces the risk of developing DMLifestyle modification reduces the risk of developing DM

Metabolic Syndrome: Risk of Developing DMMetabolic Syndrome: Risk of Developing DMDiabetes Prevention Program (DPP)

Knowler WC et al. NEJM 2002;346:393-403

*Includes 7% weight loss and at least 150 minutes of physical activity per week

Placebo

Metformin

Lifestyle modification

Inci

denc

e of

DM

(%

)

20

40

0 1 42 3

38

Diabetes Mellitus Recommendations


Goal: Hb A1c < 7%


Lifestyle and pharmacotherapy to achieve near normal HbA1C (<7%).

Vigorous modification of other risk factors (e.g., physical activity, weight management, blood pressure control, and cholesterol management as recommended).

Coordinate diabetic care with patient’s primary care physician or endocrinologist. )

HbA1c = Glycosylated hemoglobin


39

Antiplatelet Agents / Anticoagulation Antiplatelet Agents / Anticoagulation RecommendationsRecommendations

40

Aspirin RecommendationsAspirin Recommendations

Start and continue indefinitely aspirin 75 to 162 mg/d in all patients unless contraindicated

For patients undergoing CABG, aspirin (100 to 325 mg/d) should be started within 48 hours after surgery to reduce saphenous vein graft closure

Post-PCI-stented patients should receive 325 mg per day of aspirin for 1 month for bare metal stent, 3 months for sirolimus-eluting stent and 6 months for paclitaxel-eluting stent




41

Start and continue clopidogrel 75 mg/d in combination with aspirin

for post ACS or post PCI with stent placement patients for up to 12 months

for post PCI-stented patients>1 month for bare metal stent, >3 months for sirolimus-eluting stent >6 months for paclitaxel-eluting stent

*Clopidogrel is generally given preference over Ticlopidine because of a superior safety profile


Clopidogrel RecommendationsClopidogrel Recommendations

42

Anticoagulation RecommendationsAnticoagulation Recommendations

Manage warfarin to international normalized ratio 2.0 to 3.0 for paroxysmal or chronic atrial fibrillation or flutter, and in post-MI patients when clinically indicated (e.g., atrial fibrillation, LV thrombus.)

Use of warfarin in conjunction with aspirin and/or clopidogrel is associated with increased risk of bleeding and should be monitored closely



43

Aspirin Evidence: Secondary PreventionAspirin Evidence: Secondary Prevention

Antithrombotic Trialist Collaboration. BMJ 2002;324:71–86.

Category % Odds Reduction

Acute myocardial infarction

Acute stroke

Prior myocardial infarction

Prior stroke/transient ischemic attack

Other high risk

Coronary artery disease(e.g. unstable angina, heart failure)

Peripheral arterial disease(e.g. intermittent claudication)

High risk of embolism (e.g. atrial fibrillation)

Other (e.g. diabetes mellitus)

All trials

1.00.50.0 1.5 2.0 Control better Antiplatelet better

Effect of antiplatelet therapy* on vascular events**

*Aspirin was the predominant antiplatelet agent studied**Vascular events include MI, stroke, or death

44

Aspirin Evidence: Dose and EfficacyAspirin Evidence: Dose and Efficacy

0.5 1.0 1.5 2.0

500-1500 mg 34 19

160-325 mg 19 26

75-150 mg 12 32

<75 mg 3 13

Any aspirin 65 23

Antiplatelet Better Antiplatelet Worse

Aspirin Dose No. of Trials (%)Odds Ratio for

Vascular Events

0

P<.0001

Indirect Comparisons of Aspirin Doses on Vascular Events in High-Risk Patients

Antithrombotic Trialists Collaboration. BMJ. 2002;324:71-86

45

Clopidogrel Evidence: ACS (Non-STEMI and UA)Clopidogrel Evidence: ACS (Non-STEMI and UA)Clopidogrel in Unstable Angina to Prevent Recurrent Events

(CURE) Trial

The CURE Trial Investigators. NEJM. 2001;345:494-502

NSTEMI-ACS=Non ST-segment elevation acute coronary syndrome

0.00

0.02

0.04

0.06

0.08

0.10

0.12

0.14

3 6 90 12

Rat

e of

dea

th,

myo

card

ial i

nfar

ctio

n,

or s

trok

e

P<0.001

Months of Follow Up

Aspirin + Clopidogrel

Aspirin + Placebo

12,562 patients with a NSTEMI-ACS randomized to daily aspirin (75-325 mg) or clopidogrel (300 mg load, 75 mg thereafter) plus aspirin (75-325 mg) for 3-12

months (average 9 months)

46Steinhubl S et al. JAMA 2002; 288:2411-20

Clopidogrel for the Reduction of Events during Observation (CREDO) Trial

Clopidogrel Evidence: Post PCIClopidogrel Evidence: Post PCI

DAP=Dual antiplatelet therapy, PCI=Percutaneous coronary intervention, RRR=Relative risk reduction

*Dual antiplatelet therapy=Aspirin (75-325 mg daily) plus Clopidogrel (300 mg load followed by 75 mg daily).

0 123 6 90

Ris

k of

MI,

Str

oke,

or

Dea

th (

%)

27% RRR, P=0.02

10

5

15 4 weeks of DAP1 year of DAP

Months from Randomization

22,116 patients undergoing PCI randomized to 4 weeks of DAP* followed by aspirin (75-325 mg) monotherapy vs persistent DAP* for 1 year

47

Renin-Angiotensin-Aldosterone Renin-Angiotensin-Aldosterone System Blockers RecommendationsSystem Blockers Recommendations

48

ACE Inhibitor RecommendationsACE Inhibitor Recommendations

Use in all patients with LVEF < 40%, and those with diabetes or chronic kidney disease indefinitely, unless contraindicated

Consider for all other patients

Among lower risk patients with normal LVEF where cardiovascular risk factors are well controlled and where revascularization has been performed, their use may be considered optional



ACE=Angiotensin converting enzyme, LVEF= left ventricular ejection fraction


49

Angiotensin Receptor Blocker Angiotensin Receptor Blocker RecommendationsRecommendations

Use in patients who are intolerant of ACE inhibitors with HF or post MI with LVEF less than or equal to 40%.

Consider in other patients who are ACE inhibitor intolerant.

Consider use in combination with ACE inhibitors in systolic dysfunction HF.


ACE=Angiotensin converting enzyme inhibitor, LVEF=Left Ventricular Ejection fraction, HF=Heart failure, MI=Myocardial infarction



50

Aldosterone Antagonist Aldosterone Antagonist RecommendationsRecommendations

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII Use in post MI patients, without significant renal dysfunction or hyperkalemia, who are already receiving therapeutic doses of an ACE inhibitor and beta blocker, have an LVEF < 40% and either diabetes or heart failure

ACE=Angiotensin converting enzyme inhibitor, LVEF=Left Ventricular Ejection fraction, MI=Myocardial infarction

*Contraindications include abnormal renal function (creatinine >2.5 mg/dL in men or >2.0 mg/dL in women) and hyperkalemia (K+ >5.0 meq/L)

51

Years

Pro

babili

ty o

f Event

0

0.05

0.15

0.2

0.25

0.3

0 1 2 3

0.35

0.4

4

ACE-I

Placebo

OR: 0.74 (0.66–0.83)OR: 0.74 (0.66–0.83)0.1

Flather MD, et al. Lancet. 2000;355:1575–1581

SAVERadionuclideEF 40%

AIREClinical and/or radiographic signs of HF

TRACEEchocardiogramEF 35%

ACE Inhibitor Evidence: Post MI with LVD or HFACE Inhibitor Evidence: Post MI with LVD or HF

ACE-I=Angiotensin converting enzyme inhibitors, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction, OR=Odds ratio

52

ACE Inhibitor Evidence: CAD, CVD, PVD or DMACE Inhibitor Evidence: CAD, CVD, PVD or DM

Days of Follow-Up

CV

dea

th, M

I, or

st

roke

(%

)

22% RRR, P<0.0010.00

0.05

0.10

0.15

0.20

0 500 1000 1500

Placebo

Ramipril

HOPE Investigators. NEJM 2000;342:145-153

Heart Outcomes Prevention and Evaluation (HOPE) Study

ACE-I=Angiotensin converting enzyme inhibitors, DM=Diabetes mellitus, CV=Cardiovascular, HF=Heart failure, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction

9,9,297 patients with DM or vascular disease plus one additional CV risk factor, but without HF or known LVSD randomized to ramipril (10 mg) or placebo for 5 years

53

0 0.5 1 1.5 2

Cardiovascular death (0.86; 0.72-1.03)Non-fatal MI (0.78; 0.20-0.90)

Cardiac arrest (0.54; 0.20-1.47)

Combined endpoint (0.80; 0.71-0.91)

ACE Inhibitor Evidence: CADACE Inhibitor Evidence: CADEuropean Trial on Reduction of Cardiac Events with

Perindopril in Stable Coronary Artery Disease (EUROPA)

Favors Perindopril Favors Placebo

EUROPA Investigators. Lancet 2003;362:782-788

13,655 patients with CAD and presumed normal left ventricular function 13,655 patients with CAD and presumed normal left ventricular function randomized to perindopril (8 mg) or placebo for 4.2 yearsrandomized to perindopril (8 mg) or placebo for 4.2 years

ACE-I=Angiotensin converting enzyme inhibitors, CAD=Coronary artery disease, CV=Cardiovascular, MI=Myocardial infarction

54

ACE Inhibitor Evidence: CADACE Inhibitor Evidence: CADPrevention of Events with Angiotensin Converting Enzyme

Inhibition (PEACE) TrialP

rimar

y E

nd P

oint

(%

)*

30

25

20

15

10

5

00 1 2 3 4 5 6

Years After Randomization

PlaceboTrandolapril

PEACE Trial Investigators. NEJM 2004;351:2058-2068

*Includes death from cardiovascular causes, myocardial infarction, or coronary revascularization

8,290 patients with stable coronary artery disease and normal left ventricular function randomized to trandolapril (4 mg) or placebo for 4.8 years

55

ACE Inhibitor Evidence: Secondary PreventionACE Inhibitor Evidence: Secondary Prevention

Comparison between the HOPE and PEACE trials

Braunwald, E. et al., NEJM 2004;351:2058-68.

CHD=Coronary heart disease, MI=Myocardial infarction

*Reflects greater blood pressure control, revascularization, and use of other risk-reducing medications (i.e., antiplatelet therapy, -blocker, lipid-lowering medication)

0

5

10

15

20

0 1 2 3 4 5

HOPE, placebo

HOPE, active drug (ramipril)

PEACE, placebo

MI,

Car

diac

dea

th,

or S

trok

e (%

)

Years

56

ARB Evidence: Post MI with LVD or HFARB Evidence: Post MI with LVD or HF

Pfeffer M et al. NEJM 2003;349:1893-1906.

Valsartan in Acute Myocardial Infarction Trial (VALIANT)

0.0

0.1

0.2

0.3

0.4

0 6 12 18 24 30 36

Valsartan

Valsartan and Captopril

Captopril

All

Cau

se M

orta

lity

Months

Valsartan vs. Captopril: HR = 1.00; P = 0.982

Valsartan + Captopril vs. Captopril: HR = 0.98; P = 0.726

EF=Ejection fraction, HR=Hazard ratio, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction, RAS=Renin angiotensin system

14,703 patients with post-MI HF or LVSD (EF <0.40) randomized to captopril (50 mg three times daily), valsartan (160 mg twice daily), or captopril (50 mg three times

daily) plus valsartan (80 mg twice daily) over 2 years

57

ARB Evidence: Heart FailureARB Evidence: Heart Failure

Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) Alternative Trial

Granger CB et al. Lancet. 2003;362:772-777

ACE-I=Angiotensin converting enzyme inhibitors, ARB=Angiotensin receptor blockers, EF=Ejection fraction, HF=Heart failure, LVSD=Left ventricular systolic dysfunction

0 1 2 3Years

50

HR 0.77 p=0.00040

40

30

20

10

Candesartan

Placebo

CV

Dea

th o

f H

ospi

taliz

atio

n fo

r H

F

2,028 patients with symptomatic HF, LVSD (EF <40%), and intolerance to ACE-I randomized to candesartan (32 mg) or placebo over 34 months

58

ARB Evidence: Heart FailureARB Evidence: Heart Failure

0 1 2 3

0

10

20

30

40

50

3.5

HR 0.85, p=0.011

Candesartan

Placebo

CV

Dea

th o

f H

ospi

taliz

atio

n fo

r H

F

Years

Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) Added Trial

ACE-I=Angiotensin converting enzyme inhibitors, ARB=Angiotensin receptor blockers, EF=Ejection fraction, HF=Heart failure, LVSD=Left ventricular systolic dysfunction, RAS=Renin angiotensin system

McMurray JJ et al. Lancet. 2003;362:767-71

2,548 patients with symptomatic HF and LVSD (EF <40%) randomized to candesartan (32 mg) or placebo in addition to an ACE-I over 34 months

59

Pitt B et al. NEJM 1999;341:709-717

Aldosterone Antagonist: Heart FailureAldosterone Antagonist: Heart Failure

Randomized Aldactone Evaluation Study (RALES)

EF=Ejection fraction, HF=Heart failure, LVSD=Left ventricular systolic dysfunction, NYHA=New York Heart Association

RR = 0.70, P<0.001

Months

Sur

viva

l (%

)

3633302724211815129630

1.00

.90

.80

.70

.60

.50

0

SpironolactonePlacebo

1,663 patients with NYHA Class III or IV HF and LVSD (EF <0.35) randomized to spironolactone (25 mg) or placebo (50 mg) for 24 months

60

Aldosterone Antagonist: Post MI HF Aldosterone Antagonist: Post MI HF and LVSDand LVSDEplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and

Survival Study (EPHESUS)

RR = 0.85, P=0.008

6 12 18 24 30 360

5

10

15

20

25

0

All

Cau

se M

orta

lity

(%)

Month

EplerenonePlacebo

6,644 patients with evidence of heart failure and LVSD (EF <0.40) after a MI randomized to eplerenone (50 mg) or placebo for 16 months

Pitt B et al. NEJM 2003;348:1309-21

EF=Ejection fraction, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction

61

-blocker Recommendations-blocker Recommendations

62

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIIIStart and continue indefinitely in all post MI, ACS, LV dysfunction with or without HF symptoms, unless contraindicated.

Consider chronic therapy for all other patients with coronary or other vascular disease or diabetes unless contraindicated.

*Precautions but still indicated include mild to moderate asthma or chronic obstructive pulmonary disease, insulin dependent diabetes mellitus, severe peripheral arterial disease, and a PR interval >0.24 seconds.

MI=Myocardial infarction, HF=Heart Failure

-blocker Recommendations-blocker Recommendations


63

Phase of Treatment

Acute treatment

Secondaryprevention

Overall

Total #Patients

28,970

24,298

53,268

0.5 1.0 2.0RR of death

-blockerbetter

RR (95% CI)

Placebobetter

0.87 (0.77-0.98)

0.77 (0.70-0.84)

0.81 (0.75-0.87)

-blocker Evidence-blocker Evidence

Antman E, Braunwald E. Acute Myocardial Infarction. In: Braunwald E, Zipes DP, Libby P, eds. Heart Disease: A textbook of Cardiovascular Medicine, 6th ed., Philadelphia, PA: W.B. Sanders, 2001, 1168.

Summary of Secondary Prevention Trials of -blocker Therapy

CI=Confidence interval, RR=Relative risk

64

6,644 patients with LVEF <0.40 after a MI with or without HF randomized to carvedilol or placebo for 24 months

The CAPRICORN Investigators. Lancet. 2001;357:1385–1390.

RR 0.77 P=.03

0.7

0.75

0.8

0.85

0.9

0.95

1

0 0.5 1 1.5 2 2.5

Carvedilol

Placebo

Years

Pro

po

rtio

n E

ven

t-fr

ee

n=975

n=984

-blocker Evidence: Post MI with -blocker Evidence: Post MI with Left Ventricular DysfunctionLeft Ventricular Dysfunction

Carvedilol Post-Infarct Survival Control in LV Dysfunction (CAPRICORN)

65

Study Drug

HF Severity

Patients (n)

Follow-up (years)

Mean Dosage

Effects on Outcomes

CIBIS Bisoprolol* Moderate-Severe

641 1.9 3.8 mg/day

All cause mortality 22% (p=NS)

CIBIS-II Bisoprolol* Moderate-Severe

2,647 1.3 7.5mg/day

All cause mortality34% (P<0.0001)

BEST Bucindolol* Moderate-Severe

2,708 2.0 152mg/day

All cause mortality 10% (p=NS)

MERIT-HF Metoprolol succinate#

Mild-Moderate

3,991 1.0 159mg/day

All cause mortality34% (P=0.0062)

MDC Metprolol tartrate*

Mild-Moderate

383 1.0 108mg/day

Death or Need for Tx 30% (P=NS)

CAPRICORN Carvedilol Mild 1,989 1.3 40mg/day

All cause mortality 23% (P =0.03)

US Carvedilol Carvedilol Mild-Moderate

1,094 0.5 45mg/day

All-cause mortality†65% (P=.0001)

COPERNICUS Carvedilol Severe 2,289 0.9 37mg/day

All-cause mortality35% (P =0.0014)

-blocker Evidence: Benefit in HF and LVSD-blocker Evidence: Benefit in HF and LVSD

*Not an approved indication†Not a planned end point. #Not approved for severe HF or mortality reduction alone

66

Influenza VaccinationInfluenza Vaccination

Patients with cardiovascular disease should have influenza vaccination


67

Influenza Vaccination EvidenceInfluenza Vaccination Evidence

Community cohort of 140,055 subjects in the 1998–1999 season of which 55.5 % were immunized.Nichol et al. N Engl J Med 2003;348:1322-32.

Hospitalization

VaccinatedSubjects

(N=77,738)

UnvaccinatedSubjects

(N=62,317)

Adjusted Odds Ratio P value

Pneumonia or influenza 495 (0.6) 581 (0.9)0.68

(0.60–0.78)<0.001

Cardiac disease 888 (1.1) 1026 (1.6)0.81

(0.73–0.89)<0.001

Ischemic heart disease 457 (0.6) 535 (0.9)0.80

(0.70–0.91)0.001

Heart failure 466 (0.6) 538 (0.9)0.81

(0.70–0.92)0.002

Cerebrovascular disease 398 (0.5) 427 (0.7)0.84

(0.72–0.97)0.018

Death 943 (1.2) 1361 (2.2)0.52

(0.47–0.57)<0.001

Hospitalization or death 2387 (3.1) 2910 (4.7)0.65

(0.62–0.70)<0.001

Effectiveness of Influenza Vaccination during the Influenza Seasons

68

The Need to Implement Secondary The Need to Implement Secondary PreventionPrevention

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 to provide practitioners with useful reminder clues based on the guidelines, and continuously assess the success achieved in providing these therapies to the patients who can benefit from them be implemented.

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

69

AHA GWTG ProgramAHA 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.

70

Demographics 6 clicks

Clinical/Lab 8 clicks

Dischargemeds and interventions 7 clicks

Interactivelychecks patient’sdata with theAHA guidelines

SIMPLE, ONE PAGE, ON-LINE FORM SIMPLE, ONE PAGE, ON-LINE FORM

©2001 Outcome Sciences, Inc.

71

Impact of AHA Get With The Guidelines-CAD Impact of AHA Get With The Guidelines-CAD Program on Quality of CareProgram on Quality of Care

93

79

64 6757

95

83

6570 70

9787

6573 76

9687

6775 75

9791

6874

82

0102030405060708090

100

Aspirin Beta Blocker ACE Inhibitor Lipid Rx SmokingCessation

Baseline Q1 Q2 Q3 Q4* ***

* p< 0.05 compared to baseline

* *

***

*

**

GWTG-CAD: 123 US Hospitals n=27,825Labresh, Fonarow et al. Circulation 2003;108:IV-722

**

72

AHA/ACC Secondary Prevention for Patients with AHA/ACC Secondary Prevention for Patients with Coronary Artery and Other Atherosclerotic Vascular Coronary Artery and Other Atherosclerotic Vascular DiseaseDisease


73

• Evidence confirms that aggressive comprehensive risk factor management improves survival, reduces recurrent events and the need for interventional procedures, and improves the quality of life for these patients.

• Every effort should be made to ensure that patients are treated with evidence-based, guideline recommended, life-prolonging therapies in the absence of contraindications or intolerance.

Secondary Prevention ConclusionsSecondary Prevention Conclusions

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