Acute Coronary Syndromes - OSU Center for Continuing ... - PDF of Slides.pdf · Acute Coronary Syndrome (NSTE-ACS) Vincent J. Pompili, M.D., FACC Professor of Internal Medicine Director

1

Non-ST-Segment ElevationAcute Coronary Syndrome

(NSTE-ACS)Vincent J. Pompili, M.D., FACCProfessor of Internal Medicine

Director of Interventional CardiologyThe Ohio State University

Richard M. Ross Heart Hospital

Non-ST-Segment Elevation Acute Coronary Syndrome

• Pathology, Pathophysiology, and Epidemiology• Risk and Risk Stratification• Initial Therapies and Management• Platelets and Anti-Platelet Therapies• Anti-Thrombin Studies and Recommendations• Early Invasive Strategy• Peri- and Post-Discharge Medications and

Management

Pathology, Pathophysiology, and

Epidemiology

The Vulnerable Plaque

Reproduced with permission from Falk E, et al. Circulation. 1998;92:657-671.

Large Lipid Core

Thin, Vulnerable, Fibrous Cap

2

Ruptured Plaque with Occlusive Thrombus Formation

Reproduced with permission from Falk E, et al. Circulation. 1998;92:657-671.

ThrombusFormation

Atherothrombosis: Thrombus Superimposed on Atherosclerotic Plaque

Adapted with permission from Falk E, et al. Circulation. 1998;92:657-671. Slide reproduced with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org.

Characteristics of Unstable and Stable Plaque

Adapted with permission from Libby P. Circulation. 1995;91:2844-2850. Slide reproduced with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org.

Thin fibrous cap

Inflammatory cells

FewSMCs

Erodedendothelium

Activatedmacrophages

Thickfibrous cap

Lack ofinflammatory cells

Foam cells

Intactendothelium

MoreSMCs

Unstable Stable

Systemic and Focal Plaque Rupture by IVUS in ACS Patients Undergoing PCI

Adapted from Rioufol G, et al. Circulation. 2002;106:804-808.Slide courtesy of David Kandzari.

Plaque rupture at site of culprit

lesion

Plaque rupture elsewhere than site of culprit

lesion

Plaque rupture in different artery than

culprit lesion

%

%%

Analysis of 72 Arteries (n=24 TnI-positive ACS Patients)

% P

laqu

e ru

ptur

e

37.5

79.070.8

0

25

50

75

100

3

Frequency of multiple active plaque ruptures beyond the culprit lesion.

Patie

nts

(%)

80% of Patients With ≥2 Plaques

0

5

10

15

20

25

30

0 1 2 3 4 5

N=24

Frequency of Multiple “Active”Plaques in Patients With ACS

ACS indicates acute coronary syndrome.Adapted from Rioufol G, et al. Circulation. 2002;106:804-808. Slide reproduced with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org.

Thrombus Formation and ACS

UA NQMI STE-MI

Plaque Disruption/Fissure/Erosion

Thrombus Formation

Non-ST-Segment Elevation Acute Coronary Syndrome (ACS)

ST-Segment Elevation

Acute Coronary Syndrome

(ACS)

Old Terminology:

NewTerminology:

Atherothrombosis* is theLeading Cause of Death Worldwide1

*Atherothrombosis defined as ischemic heart disease and cerebrovascular disease.1The World Health Report 2001. Geneva: WHO; 2001. Reprod.with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org.

22.3

19.3

12.6

9.7

9

6.3

0 5 10 15 20 25 30

Atherothrombosis*

Infectious Disease

Cancer

Injuries

Pulmonary Disease

AIDS

Causes of Mortality (%)

* Based on data from the ARIC study of the National Heart, Lung, and Blood Institute, 1987-1994. Includes Americans hospitalized with definite or probable MI or fatal CHD, not including silent MIs. ACS indicates acute coronary syndrome; MI, myocardial infarction; ARIC, Atherosclerotic Risk in Communities; and CHD, coronary heart disease. From American Heart Association. Heart Disease and Stroke Statistics—2003 Update.

Epidemiology of ACS in the United States

• Single largest cause of death515,204 US deaths in 20001 in every 5 US deaths

• Incidence1,100,000 Americans will have a new or recurrent coronary attack each year and about 45% will die*550,000 new cases of angina per year

• Prevalence12,900,000 with a history of MI, angina, or both

Slide reproduced with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org.

4

Risk and Risk Stratification

GUSTO IIb: Correlation of 6-Month Mortality With Baseline ECG

Findings in Patients With ACS

Cum

ulat

ive

Mor

talit

y (%

)

0

2

4

6

8

10

0 30 60 90 120 150 180

Days From Randomization

T-wave inversion

ST ↓ ACS

STEMI with fibrinolytics

GUSTO indicates Global Use of Strategies To Open Occluded Arteries in Acute Coronary Syndromes; ECG, electrocardiogram; ACS, acute coronary syndrome; and STEMI, ST-segment elevation myocardial infarction.Figure adapted with permission from Savonitto S, Ardissino D, Granger CB, et al. Prognostic value of the admission electrocardiogram in acute coronary syndromes. JAMA. 1999;281:707-713. Copyright © 1999, American Medical Association. All rights reserved.


Braunwald Classification of Risk for Patients with Unstable Angina

NormalSlightly elevated (TnT >0.01 but <0.1 ng/mL)

Elevated (TnT or TnI >0.1 mg/mL)

Cardiac Markers

Normal or unchanged ECG during an episode of chest discomfort

•T-wave inversions >0.2 mV•Pathological Q waves

•Angina at rest with transient ST-segment changes >0.05 mV•New or presumed new BBB•Sustained ventricular tachycardia

ECG

Age > 70 years•Pulmonary edema•New or worsening MR murmur•S3 or new/worsening rale•Hypotension, bradycardia, tachycardia•Age >75 years

Clinical Findings

New-onset or progressive CCS Class III or IV angina the past 2 weeks

Prolonged (>20 min) rest angina, now resolved, with moderate or high likelihood of CAD

Prolonged ongoing (>20 min) rest pain

Character of Pain

Prior MI, peripheral or cerebrovascular disease, CABG, or prior aspirin use

Accelerating tempo of ischemic symptoms in preceding 48 hrs

History

Low RiskNo high- or intermediate-risk feature but may have any of the following features:

Intermediate RiskNo high-risk feature but must have 1 of the following:

High RiskAt least 1 of the following features must be present:

Feature

Available at: www.acc.org/clinical/guidelines/unstable/unstable.pdf.

TIMI Risk Score• Age >65 years• >3 CAD Risk Factors• Prior Coronary Stenosis >50 % • ST deviation• >2 Anginal events <24 hours• ASA in last 7 days• Elevated Cardiac Markers (CK-MB or troponin)

Reproduced with permission from Antman EM, Cohen M, Bernink PJ, et al. The TIMI risk score for unstable angina/non-ST elevation MI: a method for prognostication and therapeutic decision making. JAMA. 2000;284:835-842. Copyright © 2000, American Medical Association. All rights reserved.

5

The TIMI Risk Score and Incidence of Adverse Ischemic

Events in Patients with NSTE-ACS

Reproduced with permission from Antman EM, Cohen M, Bernink PJ, et al. The TIMI risk score for unstable angina/non-ST elevation MI: a method for prognostication and therapeutic decision making. JAMA.. 2000;284:835-842. Copyright © 2000, American Medical Association. All rights reserved.

4.78.3

13.219.9

26.2

40.9

0

10

20

30

40

50

0/1 2 3 4 5 6/7Number of Risk Factors

Dea

th, M

I, or

Urg

ent

Rev

ascu

lariz

atio

n (%

)

Troponin I Levels and Mortality in Patients with NSTE-ACS

Adapted with permission from Antman EA, Tanasijevic MJ, Thompson B, et al. Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. N Engl J Med. 1996;335:1342-1349. Copyright © 1996, Massachusetts Medical Society. All rights reserved.

0

2

4

6

8

0-<0.4

0.4-<1.0

1.0-<2.0

2.0-<5.0

5.0-<9.0

>9.0

% M

orta

lity

at 4

2 D

ays

Troponin I Level

Prognostic Value of Troponin T or I in ACS: A Meta-Analysis

1.9

6.76.4

20.8

0

5

10

15

20

25

Death Death/MI

%

RR 3.9(2.9-5.3)

RR 3.8(2.6-5.5)

NegPos (Trop I + T)

Figure reproduced with permission from Heidenreich PA, Alloggiamento T, Melsop K, et al. The prognostic value of troponin in patients with non-ST elevation acute coronary syndrome: a meta-analysis. J Am Coll Cardiol. 2001;38:478-485. Slide modified with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org.

Initial Therapies and Management

6

• Bed rest• Continuous ECG Monitoring• Supplemental O2 to maintain SaO2 >90%• NTG (IV or PO as dictated clinically)• Beta-blockers (PO and/or IV)• IV Morphine prn pain, anxiety, and/or CHF• IABP for hemodynamic instability• ACEI for persistent hypertension in patients with

LV systolic dysfunction or CHF

ACC/AHA Class I Recommendations for Initial Management and

Anti-Ischemic Therapy


Platelets and Anti-Platelet Therapies

Pathogenesis of Acute Coronary Syndromes:The integral role of platelets

PlaqueFissure or Rupture

PlateletAggregation

PlateletActivation

PlateletAdhesion

ThromboticOcclusion

Adhesion

The Role of Platelets in Atherothrombosis

Aggregation3

Reproduced with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org.

1

Activation2

7

ADP

•Ticlopidine•Clopidogrel

•Heparin•LMW Heparin

•Direct Thrombin Inhibitors

•Aspirin

Collagen ArachidonicAcid

Thrombin

IIb/IIIareceptors

fibrin

The Platelet

•GP IIb/IIIa inhibitors

Epinephrine

Platelet Inhibition With GP IIb/IIIa Inhibitors

Reproduced with permission from Yeghiazarians Y, Braunstein JB, Askari A, et al. Unstable angina pectoris. N Engl J Med. 2000;342:101-114. Copyright © 2000, Massachusetts Medical Society. All rights reserved.

placebo aspirin heparin ASA+hep0

2

4

6

8

10

12

% D

evel

opin

g M

I

Treatment

Treatment of Unstable AnginaResults of a study from the Montreal Heart Institute

Data from Theroux P, Quimet H, McCans J, et al. Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med. 1988;319:1105-1111.

Reproduced with permission from Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345:494-502. Copyright © 2001, Massachusetts Medical Society. All rights reserved.

2

4

6

8

10

12

14

% W

ith E

vent

Clopidogrel + Aspirin

3 6 9

Placebo + Aspirin

Follow-up (months)

P =.00009

0 12

20%RRR

The Primary Composite End Point in the CURE Trial

8

0.7911.5%14.3%ST Changes

0.8110.7%13.1%Enzyme Elevation

0.798.1%10.1%No Post-RandomRevascularization

0.8111.4%13.9%Post-Randomization Revascularization

0.798.8%10.9%No Enzyme Elevation

0.807.0%8.7%No ST Changes

RRPlavixPlaceboSubgroup

CURE: Primary End Point in Subgroups

Data from Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345:494-502.

NA0.938.8%9.4%Refract Ischemia

0.00040.8816.68%19.02%CV Death/MICVA/Ref Ischemia

0.031.343.6%2.7%Major Bleeding

NA0.851.2%1.4%Stroke

<0.010.775.19%6.68%MI

NA0.925.06%5.4%CV Death

0.000050.809.28%11.7%CV Death/ MI/CVA

P ValueRRPlavixPlaceboEndpoint

CURE Secondary End Points

Data from Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345:494-502.

PURSUIT Primary End Point

Reproduced with permission from the PURSUIT Trial Investigators. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. Platelet glycoprotein IIb/IIIa in unstable angina: Receptor Suppression Using Integrilin Therapy. N Engl J Med.1998;339:436-443. Copyright © 1998, Massachusetts Medical Society. All rights reserved.

PURSUIT Primary Composite End Point

Not powered for statistical analysis

Reproduced with permission from the PURSUIT Trial Investigators. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. Platelet glycoprotein IIb/IIIa in unstable angina: Receptor Suppression Using Integrilin Therapy. N Engl J Med.1998;339:436-443. Copyright © 1998, Massachusetts Medical Society. All rights reserved.

% W

ith D

eath

or M

I

02468

10121416

Integrilin

9.1%7.6%

11.6%

10.1%

15.7%14.2%

96 Hrs 7 Days 30 Days

Placebo

P=0.01

P=0.02

P=0.04

9

Meta-Analysis of IV GP IIb/IIIa Inhibitors inNSTE-ACS: Death or MI at 30 Days

PRISM 7.1% 5.8%* 0.80 0.60-1.06

PRISM-PLUS 12.0% 8.7% 0.70 0.50-0.9813.6%* 1.17 0.80-1.70

PARAGON-A 11.7% 10.3% 0.87 0.58-1.2912.3% 1.06 0.72-1.55

PURSUIT 15.7% 13.4% 0.83 0.70-0.9914.2% 0.89 0.79-1.00

PARAGON-B 11.4% 10.6% 0.92 0.77-1.09

GUSTO-IV 8.0% (24h) 8.2% 1.02 0.83-1.24(48h) 9.1% 1.15 0.94-1.39

Overall 11.8% 10.8%t 0.91 0.85-0.98

Odds RatioPlacebo IV Gp IIb/IIIa 95% CI

Placebo BetterGp IIb/IIIa Better0 1.0 2.0

Study

P=.015* Without heparin. † With/without heparin. (l), Low dose; (h), High-dose. Adapted with permission from Boersma E, Harrington RA, Moliterno DJ, et al. Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndrome: a meta-analysis of all major randomised clinical trials. Lancet. 2002;359:189-198.


GP IIb/IIIa Inhibitor NSTE-ACS Studies AnalysisRisk-Adjusted Mortality at 30 Days

Data from (1) Peterson ED, Pollack CV Jr, Roe MT, et al. Early use of glycoprotein IIb/IIIa inhibitors in non-ST-elevation acute myocardial infarction: observations from the National Registry of Myocardial Infarction 4. J Am Coll Cardiol. 2003;42:45-53 and (2) Boersma E, Harrington RA, Moliterno DJ, et al. Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndrome: a meta-analysis of all major randomised clinical trials. Lancet. 2002;359:189-198. Slide reproduced with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org.

0.5 2.01.0

NRMI1

Boersma2 0.83-1.010.91

0.79-0.970.8895% CIOdds Ratio

Odds Ratio for Mortality at 30 Days

GP IIb/IIIa Inhibitor Favored(aspirin + heparin)

Control ArmFavored

(aspirin + heparin)

GP IIb/IIIa Therapy and Mortality (30 day) in Diabetics with NSTE-ACS

0.5 1.0 1.5 2.00

PARAGON APARAGON BPooled

Relative Risk of Death(versus placebo Rx)

GUSTO IVPRISM-PLUSPRISMPURSUIT

Mortality:6.2% vs. 4.6%OR=0.74 CI=0.59-0.92 P=0.007

Adapted with permission from Roffi M, et al. Circulation. 2001;104:2767-2771.

Antithrombotic and Antiplatelet Therapy in ACS

ACC/AHA Guideline Update for UA and NSTEMI. 2002.

10

SYNERGY

LMWH

ESSENCE

1994 1995 1996 1997 1998 1999 2000 2002 2003 2004 2005 20062001

CURE

Clopidogrel

Bleeding risk

Ischemic risk

GP IIb/IIIa blockers

PRISM-PLUS

PURSUIT

ACUITYTACTICS TIMI-18

Early invasive

PCI ~ 5% stents ~85% stents Drug-eluting stents

ISAR-REACT 2

Milestones in ACS Management

OASIS-5

[ Fondaparinux ]Anti-Thrombin Rx

Anti-Platelet Rx

Treatment Strategy

Heparin

Aspirin

Conservative

ICTUS

Bivalirudin

REPLACE 2

Adapted from and with the courtesy of Steven Manoukian, MD.

ACC/AHA Recommendations for Antiplatelet Therapy in Patients

with NSTE-ACS

• Class IASAClopidogrel if ASA-allergic or intolerantClopidogrel in addition to ASA if early invasive approach not plannedClopidogrel should be withheld for 5-7 days if CABG plannedGP IIb/IIIa inhibitor if cardiac cath and PCI planned


ACC/AHA Recommendations for Antiplatelet Therapy in Patients

with NSTE-ACS• Class IIa

GP IIb/IIIa inhibitor in patients with high-risk features if invasive strategy not plannedGP IIb/IIIa inhibitor in patients receiving clopidogrel if cardiac cath and PCI planned

• Class IIbGP IIb/IIIa inhibitor in patients without high-risk features and PCI not planned

• Class IIIAbciximab in patients in whom PCI is not planned


Contraindications to GP IIb/IIIa Rx

• Active or recent bleeding (4-6 weeks)• Severe hypertension (SBP >180-200 mm Hg; DBP

>110 mm Hg) • Any hemorrhagic CVA (+/- intracranial neoplasm,

AVM, or aneurysm)• Any CVA within 30 days–2 years• Major surgery or trauma within 4-6 weeks• Thrombocytopenia ( <100,000/mm3 )• Bleeding diathesis/warfarin with elevated INR• (Doses must be avoided with renal insufficiency or

failure)

11

Antithrombin Therapy Studies and

Recommendations

Comparison of Heparin + ASA vs ASA Alone

ASA indicates acetylsalicylic acid; RISC, Research on InStability in Coronary artery disease; ATACS, Antithrombotic Therapy in Acute Company Syndromes; RR, relative risk; and MI, myocardial infarction.Data from Oler A, Whooley MA, Oler J, et al. Adding heparin to aspirin reduces the incidence of myocardial infarction and death in patients with unstable angina: a meta-analysis. JAMA. 1996;276:811-815. Slide reproduced with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org.

1 10

0.67 (0.44-0.1.02)

RR: Death/MI

ASA Alone 68/655=10.4%

Heparin + ASA 55/698=7.9%

0.1

Summary Relative Risk

Theroux

RISC

Cohen 1990

ATACS

Holdright

Gurfinkel

ESSENCE Results30%

25%20%

15%

10%

0 9 13Days After Randomization

17 215

5%

25 29

Unfractionated HeparinEnoxaparin (Lovenox)

Dea

th, M

I or

Rec

urre

nt A

ngin

a

P = 0.02Risk Reduction 16.2%

Adapted with permission from Cohen M, Demers C, Gurfinkel EP, et al. A comparison of low-molecular-weight heparin with unfractionatedheparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. N Engl J Med. 1997;337:447-452. Copyright © 1997, Massachusetts Medical Society. All rights reserved

TIMI 11B: Enoxaparin vs. Heparin in NSTE-ACS

Dea

th, M

I or

Ur g

ent R

evas

cul a

ri zat

ion

Unfractionated HeparinEnoxaparin (Lovenox)

Days

20

16

12

8

4

2 4 6 8 10 12 140

16.7 %

14.2 %

p = 0.03Relative Risk Reduction = 15%

Adapted from Antman EM, et al. Circulation. 1999;100:1593-1601.

12

Guidelines for the Use of Enoxaparin in Patients with NSTE-ACS

• 1 mg/kg SQ q12 hours (actual body weight)An initial 30 mg IV dose can be considered

• Adjust dosing if CrCl <30 cc/min 1 mg/kg SQ q24 hours

• Do not follow PTT; do not adjust based on PTT• Stop if platelets ↓ by 50% or below 100,000/mm3

• If patient to undergo PCI:0-8 hours since last SQ dose: no additional antithrombin therapy8-12 hours since last SQ dose: 0.3 mg/kg IV immediately prior to PCI

ACC/AHA Recommendations for Antithrombin Therapy in Patients with NSTE-ACS

• Class IAnticoagulation with subcutaneous LMWH or intravenous UFH should be added to antiplatelet therapyDose of UFH 60-70 U/kg (max 5000) IV followed by infusion of 12-15 U/kg/hr (initial max 1000 U/hr) titrated to aPTT 1.5-2.5 times controlDose of enoxaparin 1 mg/kg subcutaneously q12 hr; the first dose may be preceded by a 30-mg IV bolus

• Class IIaEnoxaparin is preferable to UFH as an anticoagulant unless CABG is planned within 24 hours


Early Invasive Strategy Studies and

Recommendations in Patients with NSTE-ACS

Months

4%

20%

16%

12%

8%

TACTICS

1 2 3 4 5 6

15.9%

19.4%Initial Medical Rx

Early Cath + PTCA

Adapted with permission from Cannon CP, Weintraub WS, Demopoulos LA, et al. Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med. 2001;344:1879-1887. Copyright © 2001, Massachusetts Medical Society. All rights reserved.

13

TACTICS Trial Results Based on Troponin

Initial Medical RxEarly Cath + PTCA

Negative Troponin

Positive Troponin

5%10%15%20%25%

P=NS

P<0.001

Adapted with permission from Cannon CP, Weintraub WS, Demopoulos LA, et al. Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med. 2001;344:1879-1887. Copyright © 2001, Massachusetts Medical Society. All rights reserved.

TnT indicates troponin T; and ST, ST segment.Data from (1) Morrow DA, et al. JAMA. 2001;286:2405-2412 and (2) Cannon CP, et al. N Engl J Med. 2001;344:1879-1887. Slide reproduced with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org.

Benefit of Invasive Strategy by Troponin and ST Changes

Death, MI, or Rehospitalization for ACS at 6 Months

12.4

25.0*

16.0 15.3*

0

5

10

15

20

25

30

TnT – TnT +

CV

Even

ts (%

)

P=NS

15.1

24.5*

16.6 16.4*

0

5

10

15

20

25

30

No ST change ST change

P=NS

P<.001 P<.001Conservative Invasive

The Primary Composite Ischemic End Point in RITA-3

Reproduced with permission from Fox KA, Poole-Wilson PA, Henderson RA, et al. Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial. Randomised Intervention Trial of Unstable Angina. Lancet. 2002;360:743-751.

Meta-Analysis of Trials of Early Cardiac Cath and

Revascularization Versus Initial Medical Therapy Alone in Patients with NSTE-ACS

Reproduced with permission from Fox KA, Poole-Wilson PA, Henderson RA, et al. Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial. Randomised Intervention Trial of unstable Angina. Lancet. 2002;360:743-751.

14

Invasive vs Conservative Strategy for UA/NSTEMI

UA indicates unstable angina, NSTEMI, non–ST-segment myocardial infarction; ISAR, Intracoronary Stenting and Antithrombic Regimen Trial; RITA, Randomized Intervention Treatment of Angina; VANQWISH, Veterans Affairs Non-Q-Wave Infarction Strategies in Hospital study; MATE, Medicine vs Angioplasty for Thrombolytic Exclusions trial; TACTICS-TIMI18, Treat Angina with Aggrastat® and Determine Cost of Therapy with Invasive or Conservative Strategy; and FRISC, Fragmin during InStability in Coronary artery disease.

TIMI IIIB

Conservative Invasive

VANQWISH

MATE

FRISC II

TACTICS-TIMI 18

VINO

RITA-3

TRUCS

ISAR-COOL


Conclusions-Recent ACS Trials

• ICTUS—In troponin (+) patients, a selective invasive management strategy may be an option, but there was a high use of angiography and revascularization in the selective arm.

• ISAR REACT 2—Clopidogrel loading alone is not sufficient in ACS patients; Troponin (+) patients derive significant benefit with GP IIb/IIIa antagonists

• SYNERGY—Enoxaparin is an alternative in invasively managed patients, but may have slightly higher bleeding, especially when UFH is indiscriminately added in the cathlab

• OASIS 5—Fondaparinux has less bleeding than enoxaparin, non-inferior clinical outcomes at 9 days, and less death and death/MI at 6 months; UFH is probably required in the cathlab—dose unknown.

• ACUITY—Bivalirudin with provisional GPI has less bleeding than UFH/LMWH + GPI, comparable ischemic outcomes, and superior net clinical benefit. Bivalirudin + GPI is comparable to UFH/LMWH + GPI

Conclusions—Recent ACS Trials

• NSTE-ACS is common and associated with high morbidity and mortality

• Early invasive strategy is preferred in higher-risk individuals

• Early initiation of appropriate antiplatelet and antithrombin therapy is important for reduction of ischemic events

• Balancing the risk of ischemic and bleeding complications is essential to maximize clinical benefit in individual patients

• The evidence base and strategies for optimal management of NSTE-ACS continue to evolve

Conclusions—ACS Management

15

ACC/AHA Class I Recommendations for Invasive and Medical Strategies in Patients

with NSTE-ACS• Class I

An early invasive strategy in patients with any high-risk indicators:• Recurrent angina/ischemia at rest or with low-level activities• Elevated troponin• New or presumed new ST-segment depression• Recurrent angina/ischemia with CHF Sx and S3 gallop,

pulmonary edema, worsening rales, or new or worsening MR• High-risk findings on noninvasive stress testing• Depressed LVEF (<40%)• Hemodynamic instability• Sustained ventricular tachycardia• PCI with 6 months or prior CABG

In the absence of any of the above high-risk indicators, either an early conservative or an early invasive strategy

Available at www.acc.org/clinical/guidelines/unstable/unstable.pdf.

ST Elevation Acute Myocardial Infarction

(STEMI)Quinn Capers, IV, MD, FACC, FSCAI

Assistant ProfessorDirector, Peripheral Vascular Interventions,

OSU Ross Heart HospitalDirector, Cath Lab, University Hospital East

STEMI

STEMI

16

EKG: Acute anterior STEMI

Cardiac Cath Lab

Artery Opened Emergently

Before stent, artery closed,no blood flow to heart

After stent, artery open,blood flow to heart restored

17

Combination of blood clot and “plaque” removed from artery

S-T segment Elevation acute Myocardial Infarction (STEMI)• Definition: acute myocardial infarction that

occurs when coronary artery is completely occluded

• Differs from non-ST elevation MI in, which coronary artery is often not completely occluded

• Coronary artery is clogged with combination of “plaque” and thrombus

STEMI:Vascular Biology

• Normal coronary artery

• Lined with endothelial cells

• No resident inflammatory cells (monocytes/macrophages/lymphocytes

• Vasodilatory>Vasoconstriction

• Antithrombotic

• Atherosclerotic plaque

• Lined with endothelial cells

• Monocytes/macrophages infiltrate vascular wall and “destabilize” plaque

• Vasoconstriction>Vasodilatory

• Prothrombotic

• Features of the stable plaque:Thick fibrous cap separating sub-intimafrom flowing bloodHigh ratio of connective tissue: lipidsLow density of inflammatory cellsLow enzymatic activity within plaque: “cold”Less prone to rupture


18

• Features of the unstable or “vulnerable”plaque:

• Thin fibrous cap separating sub-intima from flowing blood

• High ratio of lipids to connective tissue• High density of inflammatory cells,

especially at “shoulders”• High enzymatic activity within plaque: warm• More prone to rupture


STEMI: Vascular Biology

Unstable or “vulnerable” plaque:

• Unstable angina, acute MI (Non-STEMI or STEMI)

• High systemic inflammatory state (CRP, ESR, IL1)

• “Acute coronary syndromes”

• Changing the vulnerable plaque to a quiescent, stable plaque is major focus of treatment of CAD patients

• Statins (lipid lowering drugs)

• BP control

• Inhibition of renin angiotensin system

• Tobacco avoidance


AT

STEMI: Pathophysiology

19

STEMI:Pathophysiology

• Plaque rupture (70%) or endothelial erosion (30%)

• Results in flowing blood coming in contact with plaque contents

• Plaque contents are highly thrombogenic• Plaque + overlying thrombus impairs blood

flow to myocardium

Coronary Thrombosis:Clot begets Clot

Ruptured plaquepromotes thrombin formation and

recruits platelets to site

Activated plateletsaccelerate thrombin

formation

Thrombin stimulates platelet activation

STEMI:Clinical Presentation

• ST segment elevation MI (STEMI)Severe angina, shortness of breath, or bothPhysical exam can separate high from low risk pt

–Rales on lung auscultation, gallops on cardiac auscultation, tachycardia, low BP

EKG: ST segment elevation in at least two contiguous leads

STEMI:Clinical Presentation

• To Diagnose Acute MI, 2 of these 3 must be present:

Discomfort suspicious for cardiac ischemia (usually “deep seated” chest, arm, neck, or back discomfort)EKG abnormalities consistent with ischemia or infarction (ST segment depression or elevation or T wave inversion)Elevated markers of myocardial necrosis in the bloodstream (CPK, CPK-MB, troponin I, troponin T, myoglobin)

20

Acute Coronary Syndromes:Treatment Principles

• Restore normal coronary blood flow as soon as possible (“Time is muscle”)

• Address coronary thrombosis, interrupt cycle

• Increase diameter of coronary artery to allow perfusion

• Main principle: do not delay immediate reperfusion

Acute Coronary Syndromes:Treatment Principles

• Decrease myocardial oxygen demand

• Decrease HR, BP

• Interrupt sympathetic nervous system/catecholamine stimulation of heart

STEMI:Specifics of Treatment

• Antiplatelet therapy• ASA, Clopidogrel

• Antithrombin therapy• Heparin, LMWH, other antithrombins

• Beta blocker


• Nitroglycerin

• Supplemental Oxygen

• Anxiolytic

21


• Reperfuse without delay!




• Benefits of immediate reperfusion:Improves chances of survival

Minimizes myocardial damage

STEMI:Reperfusion Therapy

• Thrombolytic therapy

• Emergent cardiac cath/angioplasty/stent

• Emergent CABG

• Thrombolytic therapyMedications that enhance endogenous clot dissolving substancesExamples: tPA, rPA, streptokinaseGiven IV, dissolve coronary thrombusLeaves behind ruptured plaqueSuccess rate: 65-75%


22


• Emergent cardiac cath/angioplasty/stent

Fastest way to open coronary artery

Most “complete” method of reperfusion

Allows risk stratification by visualizing other coronary arteries and assessing LV function and pressure

Success rate: 95%+

Fibrinolytic drug tx

• Improves survival in STEMI pts

• Works within 90 min of initiation of tx

• Initial success in 65-75% of pts

• 20-30% reocclude artery

• Intracranial bleed in approx 1%

• Artery left with severe stenosis

• Available in most, if not all hospitals

Thrombolytic Therapy vsEmergent Stent Placement

Percutaneous intervention

• Improves survival in STEMI pts

• Works within 30 min of initiating cath

• Initial success in >95% of pts

• <1% reocclude artery

• Intracranial bleed risk <0.1%

• Artery left with 0% residual stenosis

• Available in <1/3 of hospitals

• In multiple head-to-head studies, percutaneousintervention in STEMI pts proved superior to fibrinolytic drug therapy (better survival, better myocardial salvage, lower complication rates)

• Often used together (STEMI pt in small hospital placed on fibrinolytic drug, transported emergently to larger center for emergent cath)

• The point is : whether using fibrinolytic therapy or emergent coronary intervention, get the artery open as soon as possible!!! It can mean the difference between a relatively normal life, life with severe heart disease, and death.

Thrombolytic Therapy vsEmergent Stent Placement

Acute Coronary Syndromes:Treatment:STEMI

• Delays are a major problem, with delays at several steps:

• Patient delays seeking medical help (denial, poor access, social issues)

• Delay in ER staff performing EKG• Delay in EKG being presented to MD for

interpretation• Delay in drugs being mixed in pharmacy and

administered to pt• Delay in transporting pt from ER to cath lab or from

one hospital to another• Delay in cath lab staff coming in from home

23

STEMI: The Aftermath• Therapies to start before hospital discharge:

• ACE inhibitors (prevent post-MI cardiac enlargement or “remodeling”, and sudden death)

• Statins (decrease lipids and change vulnerable, rupture-prone plaques to stable plaques)

• Aldosterone receptor antagonists (improve survival in pts with severe LV dysfunction post-MI)

• (These are all in addition to ASA, clopidogrel, beta-blocker)

STEMI: Summary• Unstable or “vulnerable” plaques are lipid-

filled, tense, metabolically active, and prone to rupture, causing acute coronary syndromes

• A main focus of treating CAD pts is transforming vulnerable plaques to stable plaques. Statins are the drugs with the most evidence supporting this.

STEMI: Summary• Coronary thrombosis is a hallmark of acute

coronary syndromes• Much of the therapy for STEMI is directed at

interrupting the vicious cycle of thrombosis (e.g., ASA, clopidogrel, heparin, IIb/IIIablockers)

• In STEMI, emergent reperfusion can be life-saving, the sooner the better

• We must continue efforts to decrease delays in opening the occluded artery in STEMI pts

Documents

Acute Coronary Syndromes - OSU Center for Continuing ... - PDF of Slides.pdf · Acute Coronary Syndrome (NSTE-ACS) Vincent J. Pompili, M.D., FACC Professor of Internal Medicine Director