the abc’s of the aha/acc ischemic heart disease guidelines roger s. blumenthal, md

THE ABC’S OF THETHE ABC’S OF THEAHA/ACC Ischemic Heart AHA/ACC Ischemic Heart

Disease GUIDELINES Disease GUIDELINES

Roger S. Blumenthal, MD Professor of Medicine

Director, The Johns Hopkins Ciccarone Center For The Prevention of Heart Disease

DEFINITIONDEFINITION

PRIMARY Prevention: Modification of risk factors or prevent their development to prevent or delay the onset of CHD.

SECONDARY Prevention: Initiation of Rx to reduce recurrent CHD events in patients with CHD.

PRIMARY AND A HALF Prevention*: As individuals with subclinical CHD are identified, the distinction between primary and secondary prevention becomes blurred.

*Celermajer DS. JACC 2005;45:1994-6

CHD=Coronary heart disease

ASPIRIN RECOMMENDATIONS ASPIRIN RECOMMENDATIONS

CABG=Coronary artery bypass graft, CHD=Coronary heart disease

*To be administered within the first 48 hours after surgery in order to reduce the risk of saphenous vein graft failure. Doses >162 mg/day may be continued for up to one year.

Aspirin (75-325 mg daily) in those with known CHD or carotid artery or leg artery narrowings due to plaque.

Aspirin (100-325 mg daily) in those that have undergone CABG surgery*.

SECONDARY PREVENTION

CLOPIDOGREL EVIDENCE: SECONDARY PREVENTIONCLOPIDOGREL EVIDENCE: SECONDARY PREVENTION

CLOPIDOGREL IN UNSTABLE ANGINA TO PREVENT RECURRENT EVENTS (CURE) TRIAL

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

DAP=Dual antiplatelet therapy, NSTE-ACS=Non ST-segment elevation acute coronary syndrome

3 6 90 12

RA

TE

OF

DE

AT

H,

MY

OC

AR

DIA

L IN

FA

RC

TIO

N, O

R S

TR

OK

E

P<0.001

MONTHS OF FOLLOW UP

ASPIRIN + CLOPIDOGREL

ASPIRIN + PLACEBO

12,562 patients with a NSTE-ACS randomized to daily aspirin (75-325 mg) or clopidogrel (300 mg load, 75 mg thereafter) plus aspirin for 9 months

ACE INHIBITOR RECOMMENDATIONSACE INHIBITOR RECOMMENDATIONS


*Defined by previous MI or angiographically significant CAD.

ACE=Angiotensin converting enzyme, CAD=Coronary artery disease, CKD=Chronic kidney disease, CV=Cardiovascular, DM=Diabetes mellitus, EF=Ejection fraction, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction, SBP=Systolic blood pressure

An ACE inhibitor in those following a MI, regardless of EF or in those with CAD* along with hypertension (SBP >120 mmHg), LVSD (EF <0.40), heart failure, DM, or CKD.

Optional use of an ACE inhibitor in those with low risk CAD*, well controlled CV risk factors, a normal EF, and successful revascularization.

DAYS OF FOLLOW-UP

CV

DE

AT

H, M

I, O

R S

TR

OK

E (

%)

22% RRR, P<0.001

0.00

0.05

0.10

0.15

0.20

0 500 1000 1500

ACE INHIBITOR EVIDENCE: SECONDARY PREVENTIONACE INHIBITOR EVIDENCE: SECONDARY PREVENTION

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

9,297 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

ACE-I reduce CV events in high-risk individuals

YEARS

PR

OB

AB

ILIT

Y O

F E

VE

NT

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

ACE INHIBITOR EVIDENCE: SECONDARY PREVENTIONACE INHIBITOR EVIDENCE: SECONDARY PREVENTION

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

ACE-I provide substantial benefit in post-MI LVSD

Radionuclide

EF 40%

SAVEClinical and/or radiographic signs of HF

AIREEchocardiogram

EF 35%

TRACE

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

orta

lity

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

orta

lity

Ischemic Heart Disease Mortality

BP=Blood pressure

BLOOD PRESSURE RECOMMENDATIONSBLOOD PRESSURE RECOMMENDATIONS

Initiation or maintenance of lifestyle modification in those with a BP >120/80 mmHg.

ACE=Angiotensin converting enzyme, BP=Blood pressure, CKD=Chronic kidney disease, DM=Diabetes mellitus

*A BP >130/80 mmHg should be used for individuals with CKD or DM

Use of an ACE inhibitor and/or b-blocker in those with a BP >140/90 mmHg*. Other drugs (i.e., thiazide diuretics) should be added in order to achieve the desired BP.


Nissen S et al. JAMA 2004;292:2217-26.

BLOOD PRESSURE EVIDENCE: SECONDARY PREVENTIONBLOOD PRESSURE EVIDENCE: SECONDARY PREVENTION

COMPARISON OF AMLODIPINE VS ENALAPRIL TO LIMIT OCCURRENCES OF THROMBOSIS (CAMELOT) TRIAL

*Includes CV death, MI, cardiac arrest, coronary revascularization, hospitalization for HF or angina pectoris, stroke, TIA, development of PAD

CV

eve

nt r

ate*

0

0.25

0.20

0.10

0.05

6 12 18 24

0.15

0

Placebo

AmlodipineEnalapril

Months

Follow-up BP (mmHg)

125/77124/77130/78

BP=Blood pressure, CAD=Coronary artery disease, CV=Cardiovascular, DBP=Diastolic blood pressure, HF=Heart failure, MI=Myocardial infarction, PAD=Peripheral arterial disease, TIA=Transient ischemic attack

1,991 patients with CAD and a DBP <100 mmHg randomized to amloidipine (10 mg), enalapril (20 mg), or placebo for 2 years

A BP <130/80 mmHg is associated with fewer CV events

A -blocker in all patients following a MI.

A beta-blocker in all patients with LVSD.

*Relative contraindications include asthma, chronic obstructive pulmonary disease, insulin dependent diabetes mellitus, severe peripheral arterial disease, and a PR interval >0.24 seconds.

CV=Cardiovascular, DM=Diabetes mellitus, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction

-BLOCKER RECOMMENDATIONS*-BLOCKER RECOMMENDATIONS*


A -blocker in those with other forms of CV disease or DM, unless contraindicated.


CHOLESTEROL MANAGEMENT GUIDELINESCHOLESTEROL MANAGEMENT GUIDELINES

Restriction of saturated fat (<7% of total calories) and cholesterol (<200 mg/day) in all patients.

Promotion of daily physical activity and weight management in all patients.

Increase in -3 fatty acid consumption in all patients.

LDL-C=Low density lipoprotein cholesterol


CHOLESTEROL MANAGEMENT GUIDELINES (CONTINUED)CHOLESTEROL MANAGEMENT GUIDELINES (CONTINUED)

Initiation or intensification of LDL-C lowering drug therapy in those with a baseline or on-treatment LDL-C level >100 mg/dl.

LDL-C=Low density lipoprotein cholesterol

Initiation of LDL-C lowering drug therapy in those with a baseline LDL-C level <100 mg/dl based on clinical judgment.

CHOLESTEROL MANAGEMENT GUIDELINES (CONTINUED)CHOLESTEROL MANAGEMENT GUIDELINES (CONTINUED)

As set forth by the Adult Treatment Panel III (ATP III) National Cholesterol Education Program (NCEP)

Obtain a fasting lipid profile in all patients. For those with a myocardial infarction, a fasting lipid profile should be obtained within 24 hrs of admission.

Start therapeutic lifestyle changes in all patients, including:

• Reduced intakes of saturated fats (<7% of total calories) and cholesterol (<200 mg/day)

• Addition of plant stanols/sterols (2 g/day) and viscous fiber (10-25 g/day) to enhance LDL-C lowering

• Weight reduction

• Increased physical activity

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

RECOMMENDATIONSGOALS

Risk Category LDL-C Goal Initiate TLCConsider

Drug Therapy

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

<100 mg/dL (optional goal:

<70 mg/dL)100 mg/dL

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

options)

Moderately high risk: 2+ risk factors* (10-year risk 10% to 20%)

<130 mg/dL (optional goal: <100 mg/dL)

130 mg/dL>130 mg/dL

(100-129 mg/dL: consider drug options)

Moderate risk: 2+ risk factors* (10 year risk <10%)

<130 mg/dL 130 mg/dL >160 mg/dL

Lower risk: 0-1 risk factor*

<160 mg/dL 160 mg/dL>190 mg/dL

(160-189 mg/dL: LDL-lowering drug optional)

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

ATP III LDL-C GOALS AND CUT-POINTS FOR DRUG THERAPYATP III LDL-C GOALS AND CUT-POINTS FOR DRUG THERAPY

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

*Risk factors for cardiovascular disease include: cigarettes smoking, hypertension (blood pressure >140/90 mmHg or on antihypertensive medication, HDL-C <40 mg/dl (>60 mg/dl is a negative risk factor), family history of premature CHD, age >45 years in men or >55 years in women.

PRIMARY THERAPIES TO LOWER LDL-CPRIMARY THERAPIES TO LOWER LDL-C

Class Drug(s)

3-Hydroxy-3-Methylglutaryl Coenzyme A (HMG-CoA) reductase inhibitors [Statins]

Atorvastatin (Lipitor)

Fluvastatin (Lescol XL)

Lovastatin (generic and Mevacor)

Pravastatin (Pravachol)

Rosuvastatin (Crestor)

Simvastatin (Zocor)

Bile acid sequestrants Cholestyramine (generic and Questran)

Colesevelam (Welchol)

Colestipol (Colestid)

Cholesterol absorption inhibitor Ezetimibe (Zetia)

Dietary Adjuncts Soluble fiber

Soy protein

Stanol esters

Follow-up (months)

3 6 9 12 15 18 21 24 27 30

30

25

20

15

10

5

0

P =0.005

Rec

urr

ent

MI o

r C

ard

iac

Dea

th

16% RRR

PRAVASTATIN OR ATORVASTATIN EVALUATION AND INFECTION THERAPY (PROVE-IT)—TIMI 22 STUDY

Atorvastatin

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 PREVENTIONHMG-COA REDUCTASE INHIBITOR: SECONDARY PREVENTION

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

Acute intensive therapy significantly reduces the event rate

SCANDINAVIAN SIMVASTATIN SURVIVAL STUDY (4S)

Mo

rtal

ity

(%)

Placebo

11.5

Simvastatin

12

8

4

0

8.2

P<0.001

30% RRR

4S Group. Lancet 1994;344:1383–1389

MI=Myocardial infarction, RRR=Relative risk reduction

4,444 patients with angina pectoris or previous MI randomized to simvastatin (20-40 mg) or placebo for 5.4 years


Statins provide significant benefit in those with average LDL-C levels

Baseline

LDL-C (mg/dL)Statin

(n = 10,269)Placebo

(n = 10,267)

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

100–129 668 (18.9%) 871 (24.7%)

130 1083 (21.6%) 1356 (26.9%)

All patients 2033 (19.8%) 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)


20,536 patients with CAD, other occlusive arterial disease, or DM randomized 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

Statins provide significant benefit across a broad range of LDL-C levels

Complete cessation

No environmental tobacco smoke exposure

CIGARETTE SMOKING CESSATION GUIDELINESCIGARETTE SMOKING CESSATION GUIDELINES

Ask about tobacco use at every visit.

In a clear, strong, and personalized manner, advise the patient to stop smoking.

Urge avoidance of exposure to secondhand smoke at work and home.

Assess the patient’s willingness to quit smoking.

Develop a plan for smoking cessation and arrange follow-up.

Provide counseling, pharmacologic therapy, and referral to formal smoking cessation programs as indicated.


SMOKING CESSATION PHARMACOTHERAPY*SMOKING CESSATION PHARMACOTHERAPY*

Agent CautionSide

EffectsDosage Duration Instructions

Bupropion SR

(Zyban®)

Seizure disorder

Eating disorder

Taking MAO inhibitor

Pregnancy

Insomnia

Dry mouth

150 mg QAM

then

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.

Transdermal

Nicotine

Patch**

Within 2 weeks of a MI

Unstable angina

Arrhythmias

Decompensated heart failure

Skin reaction

Insomnia

21 mg QAM

14 mg QAM

7 mg QAM

or

15 mg QAM

4 weeks

2 weeks

2 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

JAMA 2006:296:47-55 and JAMA 2006;296:56-63

SMOKING CESSATION PHARMACOTHERAPY: VARENICLINESMOKING CESSATION PHARMACOTHERAPY: VARENICLINE

Two trials compared treatment with varenicline, a nicotine acetylcholine receptor agonist, to treatment with buproprion or placebo.

These trials included a total of almost 700 participants. The mean duration of smoking was 25 years.

Varenicline yielded higher rates of smoking cessation than buproprion or placebo.

Study 1p<0.001 for V vs Bp<0.001 for V vs P

Study 2p<0.001 for V vs Bp<0.001 for V vs P

Calculate BMI* and measure waist circumference as part of evaluation. Monitor response of BMI and waist circumference to therapy.

BMI 18.5 to 24.9 kg/m2

Women: <35 inchesMen: <40 inches

WEIGHT MANAGEMENT GUIDELINESWEIGHT MANAGEMENT GUIDELINES

Start weight management and physical activity as appropriate.

If BMI and/or waist circumference is above goal, initiate caloric restriction, measures to increase caloric expenditure, and treatment strategies for the metabolic syndrome.

BMI=Body mass index

*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.

10% weight reduction within the first year of

therapy


PREVALENCE OF OBESITY IN U.S. ADULTSPREVALENCE OF OBESITY IN U.S. ADULTS

1991 1996

2003

% State Population No Data <10% 10%–14% 15%–19% 20%–24% ≥ 25%

Source: CDC Overweight and Obesity

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.

DIABETES MELLITUS GUIDELINESDIABETES MELLITUS GUIDELINES

Goal HbA1C <7% Intensive lifestyle modification to prevent the development of DM (especially in those with the metabolic syndrome)

Aggressive management of CV risk factors (i.e., tobacco use, hypertension, dyslipidemia, physical inactivity, and overweight and obese states)

Hypoglycemic therapy to achieve normal to near normal fasting plasma glucose as defined by the HbA1C (<7%)

• Weight reduction and exercise• Oral hypoglycemic agents• Insulin therapy

Coordination of diabetic care with the patient’s primary physician and/or endocrinologist.

CV=Cardiovascular, DM=Diabetes mellitus, HbA1C=Glycosylated hemoglobin


Assess risk, preferably with exercise test, to guide prescription.

Encourage aerobic activity (e.g., walking, jogging, cycling) supplemented by an increase in daily activities (e.g., walking breaks at work, gardening, household work).

Encourage resistance training (e.g., weight machines, free weights) 2 days a week (Class IIb, Level C)

Encourage cardiac rehabilitation for patients with chronic stable angina, recent myocardial infarction, left ventricular systolic dysfunction, or recent coronary artery bypass graft surgery.

Minimum: 30 minutes,5 days per week

Optimal: 30 minutes daily

EXERCISE GUIDELINESEXERCISE GUIDELINES


EJECTION FRACTION GUIDELINESEJECTION FRACTION GUIDELINES

Echocardiography in those following a STEMI to re-evaluate ventricular function when results are used to guide therapy*.

Echocardiography or radionuclide angiography in those following a NSTE-ACS when results are used to guide therapy*.

*Includes use of an aldosterone antagonist, digitalis, and/or an implantable cardioverter defibrillator

NSTE-ACS=Non-ST-segment elevation acute coronary syndrome, STEMI=ST-segment elevation myocardial infarction


80706050403020

54-60 >60

50

40

30

20

10

0

<30

31-35

36-45

46-53

Car

diac

Mor

talit

y %

Brodie B et al. Am J Cardiol 1992;69:1113

RELATIONSHIP BETWEEN EF* AND MORTALITYRELATIONSHIP BETWEEN EF* AND MORTALITY

Ejection Fraction (%)

*Post myocardial infarction

EF=Ejection fraction

RR = 0.85, P=0.008

6 12 18 24 30 360

5

10

15

20

25

0

Month

ALDOSTERONE ANTAGONIST: SECONDARY PREVENTIONALDOSTERONE ANTAGONIST: SECONDARY PREVENTION

EPLERENONE POCT-ACUTE MYOCARDIAL INFARCTION HEART FAILURE EFFICACY AND SURVIVAL STUDY (EPHESUS)

EplerenonePlacebo

3,313 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

Aldosterone inhibition provides significant benefit in patients with post-MI heart failure and LVSD

All

Cau

se M

ort

alit

y (%

)

ICD ALGORITHMICD ALGORITHM

EF < 30%

EPS

Yes

+

NEJM 349:1836,2003

EF 31-40%

No

No ICD.Medical Rx

EF > 40%

–

AT LEAST ONE MONTH FOLLOWING A MYOCARDIAL INFARCTION

EF=Ejection fraction, EPS=Electrophysiology study, ICD=Implantable cardioverter defibrillator, Rx=Treatment, SCD=Sudden cardiac death,

1 Moss AJ. N Engl J Med. 1996;335:1933-19402 Buxton AE. N Engl J Med. 1999;341:1882-18903 Moss AF. N Engl J Med. 2002;346:877-883

1 2 3

54%

75%

55%

73%

31%

61%

27 Months 39 Months 20 Months

% M

ort

alit

y R

edu

ctio

n w

/ IC

D R

xICD: SECONDARY PREVENTION*ICD: SECONDARY PREVENTION*

*Primary prevention of sudden cardiac death

Overall death

Arrhythmic death

EF <35% EF <40% EF <30%

PREVENTION PYRAMID

ACE-1 = angiotensin converting enzyme inhibitor; ASA = aspirin

Secondary

Primary

Primordial

ASAACE-IRehab

β-blockers+Primary

LipidsHypertension

Smoking cessationDiabetes

+Primordial

Physical activityHealthy eatingIdeal weight

Psychosocial factorsFamilial predisposition

the abc’s of the aha/acc ischemic heart disease guidelines roger s. blumenthal, md

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