management of coronary artery disease: saravanan kuppuswamy md division of cardiology department of...

Management of Coronary Artery Disease:

Saravanan Kuppuswamy MDDivision of Cardiology

Department of Internal MedicineUniversity of Missouri Hospital

Coronary blood supply

Micro circulation

Temporal Trends in CAD

• CHD is the leading cause of death in adults in US (1/3 of all deaths in subjects over age 35)

• Mortality rates for cardiovascular death has fallen in most developed countries 24-28% since 1975

• Estimated that 45 percent of mortality reduction in CHD is due to improvement of medical therapy and 55% is due to risk factor modification

Etiology

• Congenital

• Acquired– Infection– Inflammation– Neoplastic

Management of CAD

• Acute

• Chronic

ACS=acute coronary syndrome.UA=unstable angina.Bhatt DL. J Invasive Cardiol. 2003;15:3B-9B.

Acute Plaque Rupture (UA/NSTEMI/STEMI)

Presence of Multiple Coronary Plaques

Persistent Hyperreactive Platelets

Vascular Inflammation

Clinical

Subclinical

ACS: The Tip of the Atherothrombotic “Iceberg”

NSTEMI=non-ST-segment elevation myocardial infarction.STEMI=ST-segment elevation myocardial infarction.

Chronic stable angina

• Levine’s sign

• Exercise capacity may vary

• Relieved by nitrates

CCS classification

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

Components of Secondary Prevention

Cigarette smoking cessation

Blood pressure control

Lipid management to goal

Physical activity

Weight management to goal

Diabetes management to goal

Antiplatelet agents / anticoagulants

Renin angiotensin aldosterone system blockers

Beta blockers

Influenza vaccination

ABCDE Of Management

Antiplatelet Agents / Anticoagulation Recommendations

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

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



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

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

Mechanism of action of nitrates

-blocker Recommendations


Start 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


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

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)

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 7.5

mg/day

All cause mortality

34% (P<0.0001)

BEST Bucindolol* Moderate-Severe

2,708 2.0 152

mg/day

All cause mortality 10% (p=NS)

MERIT-HF Metoprolol succinate#

Mild-Moderate

3,991 1.0 159

mg/day

All cause mortality

34% (P=0.0062)

MDC Metprolol tartrate*

Mild-Moderate

383 1.0 108

mg/day

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

CAPRICORN Carvedilol Mild 1,989 1.3 40

mg/day

All cause mortality 23% (P =0.03)

US Carvedilol Carvedilol Mild-Moderate

1,094 0.5 45

mg/day

All-cause mortality†

65% (P=.0001)

COPERNICUS Carvedilol Severe 2,289 0.9 37

mg/day

All-cause mortality

35% (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

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


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

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

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. ‡

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

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

Goal: Complete Cessation and No Exposure to Environmental Tobacco Smoke


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.

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

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 CHD

plus: 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

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


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.



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




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)

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

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

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

LaRosa 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

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 TGPatient

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

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*

*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

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.


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.

Grundy, 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

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 years

Lifestyle 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

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


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



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

Light or moderate exercise is associated with lower risk

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

Exercise Evidence: Mortality RiskExercise Evidence: Mortality Risk

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

Renin-Angiotensin-Aldosterone System Blockers Recommendations

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


QuickTime™ and a decompressor

are needed to see this picture.

http://www.tctmd.com/display/expert/slides/45561/

STRIVETM

STEMI

Clinical finding

EKG

Serum markers

Risk assessment

Non-cardiacchest pain

Stableangina

UA NSTEMI

Negative Positive

ST-T wave changes

ST elevation

Lowprobability

Medium-high risk

ThrombolysisPrimary PCI

Aspirin + GP IIb/IIIa inhibitor clopidogrel + heparin/

LMWH + anti-ischemic RxEarly invasive Rx

Discharge

Negative

Diagnostic rule out MI/ACS

pathway

STEMI

Negative

Atypical pain

Low risk

Aspirin, heparin/low-molecular-weight heparin (LMWH) +

clopidogrelAnti-ischemic Rx

Early conservative therapy

Ongoing pain

DM=diabetes mellitus.Cannon, Braunwald. Heart Disease. 2001.

Rest pain, Post-MI, DM, Prior Aspirin

Exertional pain

The Spectrum of ACS

Acute Coronary Syndromes:

Management of STEMI

Balloon angioplasty

Stents

Acute Coronary Syndromes:

Management of UA/NSTEMI

Acute Management of UA/NSTEMI

Anti-Ischemic Therapy• Oxygen, bed rest, ECG monitoring• Nitroglycerin -Blockers• ACE inhibitors

UA, unstable angina; NSTEMI, non-ST-segment elevation myocardial infarction; ECG, electrocardiogram; ACE, angiotensin-converting enzyme.Braunwald E, et al. J Am Coll Cardiol. 2000;36:970-1062.

Antithrombotic Therapy• Antiplatelet therapy• Anticoagulant therapy

Rationale for Use: Pharmacologic Intervention in Thrombosis

UFH=unfractionated heparin.LMWH=low-molecular-weight heparinADP=adenosine diphosphate.TFPI=tissue factor pathway inhibitor

Selwyn A. Am J Cardiol. 2003;91:3H-11H.

Coagulation cascade

Platelets

LMWH

Thienopyridines

GP IIb/IIIa inhibitors

Thrombolytics

LMWHUFH

LMWHUFH

Direct thrombininhibitors

Tissue factor

Factor Xa

Prothrombin

Thrombin

Platelets

A2 vWF ADP

Activated platelets

Fibrinogen cross-linking

Platelet aggregation

Aspirin

Fibrinogen Fibrin Fibrindegradation

Collagen Leukocytes

TFPI

Anti-thrombin

Anti-thrombin

Thromboxane

PlasminThrombus

Efficacy of Aspirin Doses on Vascular Events in High Risk Patients

Adapted with permission from the BMJ Publishing Group. Anti-thrombotic Trialists’ Collaboration. BMJ. 2002;324:71-86.

0 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

Anti - platelet Better Anti - platelet Worse

Aspirin Dose # Trials OR* (%)

*Odds reduction. Treatment effect P < 0.0001.

Odds Ratio

RR: Death/MI

ASA Alone 68/655=10.4%

Heparin + ASA 55/698=7.9%

B

B

B

B

B

B

B

0.1 1 10

Summary Relative Risk

0.67 (0.44-0.1.02)

Theroux

RISC

Cohen 1990

ATACS

Holdright

Gurfinkel

Comparison of Heparin + ASA vs ASA Alone

ASA, acetylsalicylic acid; RISC, Research on InStability in Coronary artery disease; ATACS, Antithrombotic Therapy in Acute Company Syndromes; RR, relative risk; MI, myocardial infarction.Oler A, et al. JAMA. 1996;276:811-815. (with permission)

http://www.tctmd.com/display/expert/slides/30280/

TIMI, Thrombosis in Myocardial Infarction; ESSENCE, Efficacy and Safety of Subcutaneous Enozapam in Non–Q-Wave Coronary Events; UHF, unfractionated heparin; ENOX, enoxaparin; MI, myocardial infarction; OR, odds ratio.Antman EM, et al. Circulation. 1999;100:1602-1608. (with permission)

TIMI IIB/ESSENCE Metanalysis:Enoxaparin vs Unfractionated Heparin

8.6 7.1 0.82 (0.69-0.97) 18 .02

6.5 5.2 0.79 (0.65-0.96) 21 .02

5.3 4.1 0.77(0.62-0.95) 23 .02

1.8 1.4 0.80 (0.55-1.16) 20 .24

0.5 1 2

Day

2

8

14

43

UFH(%)

ENOX(%)

OR(95 CI)

Favors ENOX

Favors UFH

P

OR

Death or MI %

LMWH Limitations

• Indirect inhibition: dependent on antithrombin• Inability to inhibit clot-bound thrombin• Catheterization lab: slower onset, longer half-life,

and with enoxaparin, no standard test to measure levels/effect

• CABG: concerns regarding the long half-life• Monitoring for Factor Xa: possible, but what is

the therapeutic target, increased time, expense?• Not all LMWHs are the same

CABG=coronary artery bypass graft.

0.00

0.02

0.04

0.06

0.08

0.10

0.12

0.14C

um

ula

tive

Haz

ard

Rat

e

Clopidogrel + Aspirin*

3 6 9

Placebo + Aspirin*

Months of Follow-Up

P<0.001N=12,562

0 12

*Other standard therapies were used as appropriate.CV=cardiovascular.

CURE Trial Investigators. N Engl J Med. 2001;345:494-502.

20%Relative-riskReduction

CURE: Primary Endpoint: MI/Stroke/CV Death

Before PCIBefore PCI Post-PCIPost-PCI

PlaceboPlacebo

GP IIb/IIIa InhibitorGP IIb/IIIa Inhibitor

PCIPCI

n=2754n=2754 pp=0.001 =0.001

+24 h +48 h

8.0%8.0%

4.9%4.9%

0%

2%

4%

6%

8%

10%

Dea

th/M

ID

eath

/MI

0

2.9%2.9%

0%

2%

4%

6%

8%

10%

n=12,296n=12,296pp=0.001=0.001

+24 h +48 h +72 h

4.3%4.3% Dea

th/M

ID

eath

/MI

Boersma E, et al. Circulation. 1999;100:2045-2048.

Early Use of GP IIb/IIIa Inhibition Improves PCI: CAPTURE, PURSUIT, PRISM-PLUS

4.59%

2.59%

0%

2%

4%

6%

8%

In-h

osp

ital

mo

rtal

ity

(%)No early

GP IIb/IIIa inhibitor (n=26,596)

Early GP IIb/IIIainhibitor (n=14,296)

In-hospital Mortality is Lower With Early GP IIb/IIIa Inhibitor Use (within 24 hrs) †

∆ 42%p<0.0001∆ 42%p<0.0001

Includes patients who received late GP IIb/IIIa inhibitor (> 24 hrs) therapy.

† Unadjusted for risk.

TIMI, thrombosis in myocardial infarction; UA, unstable angina; NSTEMI, non–ST-segment elevation myocardial infarction; CAD, coronary artery disease.Antman EM, et al. JAMA. 2000;284:835-842.

TIMI Risk Score for UA/NSTEMI: 7 Independent Predictors

– Aged ≥65 years

– ≥3 CAD risk factors

– Prior CAD (stenosis >50%)

– Aspirin in last 7 days

– >2 anginal events in ≤24 hours

– ST deviation

– Elevated cardiac markers (CK-MB or troponin)

TIMI risk score predicts 30 day mortality after a myocardial infarction

The TIMI risk score has a continuous association with 30-day mortality in patients with an ST elevation (STE) myocardial infarction who are eligible for fibrinolytic therapy.

Morrow, DA, Antman, EM, Charlesworth, A, et al Circulation 2000; 102:2031.

TIMI risk score predicts 14 day outcome for NSTEMI and UA

The TIMI risk score has a continuous association with 14-day mortality, recurrent MI and target vessel revascularization in patients with an NSTEMI and unstable angina (UA)

Antman, EM, Cohen, et al, JAMA 2000; 284:835.

STRIVETM

Chest Pain Classification/Triage

Class IClass II

Class IIIClass IV

Class VClass “x”

Class I

• STEMI

Chest pain with STE or new LBBB

• Acute revascularization followed by CICU admission

Class II• Unstable Angina/NSTEMI (high risk)

– Positive initial cardiac markers– ST depression > 1mm in two contiguous leads– TIMI risk score > 5– Continued angina requiring IV NTG drip– CHF– SBP < 90mmHg or > 180mmHg– New mitral regurgitaiton– Recent ACS (< 30 days)

• Admit to CICU by cardiology

Class III

• Unstable Angina– No initial increase in cardiac markers– Normal ECG or ST depression < 1mm– No CHF– No recent ACS– TIMI risk score 3-4

• Admit to telemetry by cardiology

Class IV

• Unstable Angina with normal ECG– No initial increase in cardiac markers– No history of CAD– TIMI risk score < 3– No ongoing or recurring pain

• Admit to Chest Pain Service or Chest Pain Center in ER

Class V

• Non-cardiac Chest Pain

• Workup in ER with appropriate referral

Class “x”

• Critical causes of acute chest pain other than ACS or ACS combined with other acute critical/life-threatening illnesses

• Admit to intensive care (MICU, SICU or CICU) as appropriate

Chest pain algorithm

management of coronary artery disease: saravanan kuppuswamy md division of cardiology department of...

Documents

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ccs classification slide

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risk procedure

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