ACUTE CORONARY SYNDROME

ACUTE CORONARY SYNDROME (ACS), including those associated with or without ST- segment

elevation, share in common pathophysiology mediated by activated platelets and thrombin superimposed on a

culprit plaque

ACS

• No ST elevation Unstable angina NSTEMI NQMI* QMI

• ST elevation QMI* NQMI

Classification A. Secondary B. Primary C. Postinfarction (< 2 weeks)

Braunwald classification of unstable angina

I New onset, severe or accelerated angina IA IB IC

II Subacute rest angina (> 48 hours ago) IIA IIB IIC

III Acute rest angina (within 48 hours) IIIA IIIB IIIC

MI:ST elevationNew bundle branch blockECG changes of posterior MIEvolution of Q waves

2 × upper limit of CK-MB, CK Troponins T > 0.2 ng/dlTroponin I > 1.0-1.5 ng/dl

       Minimal injury Aborted ST elevation MITransient ST elevationST depressionT inversionMinor non-specific ECG changes

< 2 × elevation CK-MB, CK Troponins T 0.01-0.2 ng/dl Troponin I 0.1 or 0.4 ng/dl to 1.0-1.5 ng/dl

       UA: Transient ST elevationST depressionT inversionMinor non-specific ECG changesNormal ECG

CK-MB, CK below upper limit Troponins T < 0.01 ng/dl Troponin I < 0.1 or 0.4 ng/dl

Prior risk

  -   older age (> 65 years)

  -   prior myocardial infarction or heart failure

  -   co morbidity: diabetes, hypertension

  -   impaired renal function

Acute ischemic risk

  -   refractory or recurrent ischemic pain

  -   ECG: ST segment depression or transient ST elevation during pain

  -   ECG: T wave inversion (lower risk than ST segment depression or transient ST elevation)

  -   impaired left ventricular function with ischemia

  -   release of cardiac enzymes: CK, CK-MB, troponin T or troponin I

  -   raised C reactive protein (high sensitivity assay)

Management of AMI• ASA or other anti platelets• O2• Analgesics• Anticoagulants• GP IIb/IIIa inhibitors• Nitrate• B blocker• ACEi• Thrombolytic• Mechanical reperfusion

PCI in AMI

• Primary• Rescue • Early < 4 days• Deferred > 4 days

Complication of AMI

Mechanical:• Pump failure>>shock• Free wall rupture• Interventricular

rupture• Papillary muscle

rupture>>MR• pseudo aneurysm

Arrhythmia:*Tachyarrhythmia's supraventricular ventricular*Brady arrhythmias*Bundle branch block

Other complications of AMI

• Recurrent chest pain• Recurrent MI• Pericarditis• Deep vein thrombosis>>Pulmonary emboli• Lv aneurysm• Lv thrombosis>>Arterial embolism

ADMIRAL abciximab before direct angioplasty and stenting in

myocardial infarction regarding acute and long-term follow300 pt, GP IIb/IIIa inhibitor

• Composite end point at 30 days: 6% abciximab and 14.6% in the placebo• Mortality at 30-day: 3.4% abciximab group and 6.6% in the placebo• Urgent revascularization : 1.3% abciximab and 6.6% in placebo• Mortality at 6 months: 3.4% abciximab group and 7.3% in the placebo• Composite end point at 6 months: 7.4% abciximab and 15.9% in the placebo

NEJM 2001;344

CADILLAC controlled abciximab and device investigation to lower late

angioplasty complications

2081 pt: effect of IIb/IIIa inhibitor • Primary out come at 6 m: MI, death, TVR, CVA

• Hospital mortality: 1-1.6%• Strokes: 0.4%• Re-infarction: 0.6% PTCA 0% PCTA + abciximab 0.8% stent 0.2% stent+ abciximab

TVR: 2.3% PTCA 0.2% PCTA + abciximab 0.8% stent 0.2% stent+ abciximab AHA 1999

CADILLAC controlled abciximab and device investigation to lower late

angioplasty complications

• Recurrent ischemia: • 4.9% PTCA 1.4% PTCA+ abciximab 3.9% stent 1.2% stent+ abciximab

AHA 1999

GUSTO V global use of strategies to open occluded coronary arteries

16588 pt; fibrinolytic+/- GP IIb/IIIa inhibitor

• Mortality at 24-h: 2.3% with reteplase and 2.2% in reteplase+ abciximab• Mortality at 7-d: 4,5% with reteplase and 4.3% in reteplase+ abciximab• Mortality at 30-d: 5.9% in reteplase and 5.6% in the reteplase+ abciximab• Stroke: 0.3% in reteplase and 0.2% in the reteplase+ abciximab• Re-infarction: 3.5% in reteplase and 2.3% in the reteplase+ abciximab• MACE: at 7-d: 20.6% in reteplase and 16.2% in reteplase+ abciximab

• More non-intracranial bleeding complications in the combination group • The rates of intracranial hemorrhage and non-fatal disabling stroke were

similar in patients< 75 years

Lancet 2001

STENT-PAMI primary angioplasty in myocardial infarction

PCI+/- stent in ACS 900 pt

• angina at 6 months occurred in 11.3% patients in the stent and 16.9% in angioplasty

• TVR: 7.7 % vs. 17.0% in stent and angioplasty

• The primary end point: 12.6% and 20.1% • 6-month mortality: 4.2% and 2.7%

NEJM 1999

STENT-PAMI primary angioplasty in myocardial infarction

Long term effect of PCI as compared to streptokinase for AMI395 pt

• Mortality over 5 ys was 13 % in the angioplasty, 24 % in the streptokinase

• TVR <30 ds in PCI: 12.4% and in thrombolytic: 42.8%• TVR >30 ds in PCI: 34.1% and in thrombolytic: 28.3%• Re-MI in first 30 days: 0.5 % in angioplasty and 9 % in

streptokinase.• Re-MI After 30 days: 6% in the angioplasty vs. 12% in

streptokinase• • NEJM 1999

STENTIM-2Comparison of PTCA and Stenting in AMI-2 in 211 pt

• Re-infarction: 4% in PTCA and 3.6% in stent• Repeat revascularization: 5.4% in PTCA and 5% in stent• In-hospital event free survival: 94.6% in PTCA and 95% in stent• Six-month event free survival: 72.7% in PTCA and 82% in stent• Six-month revascularization: 26.4% in PTCA and 16.8% in stent• One year revascularization: 28.2% in PTCA and 17.8% in stent• Restenosis: 39.6% in PTCA and 25.3% in stent

JACC 2000

GUSTO IV ACSeffect of GP IIb/IIIa inhibitor in7800 pt

• primary endpoint death or myocardial infarction at 30 days.

• FINDINGS: 30- day death and MI: 8.0% patients on placebo 8.2% abciximab on 24 h 9.1% on 48 h abciximab died

• This study indicates that abciximab is not beneficial as first-line medical treatment in patients admitted with acute coronary syndromes.

Lancet. 2001 Jun

GUSTO-IV PilotEarly PCI after reteplase+/- abciximab

30-day composite end point in early PCI (death, re-infarction, urgent revascularization): (5.6%) Death 3.4%, Re-vascularization 1.6% Re-infarction 1.2%

30-day composite end point in no early PCI (death, re-infarction, urgent revascularization): (16%) Re-vascularization 9.3% Re-infarction 4.9%

JACC 2000;36

STATStenting vs. Thrombolysis in AMI Trial in123 pt

• Primary end point at 6-month : 24.2% in stent vs. 55.7% in t-PA • Re-infarction: 6.5% in stent and 16.4% in t-PA• Stroke: 1.6% in stent and 4.9% in t-PA • TVR: 14.5% in stent and 49.5% in t-PA• Recurrent UA: 9.7% in stent and 26.2% in t-PA

JACC 2001

IMPACT-AMIt-PA +/- IIb/IIIa integrin receptor blockade

• The primary end point was TIMI grade 3 flow at 90-minute angiography. Secondary end points were time to ST-segment recovery, an in-hospital composite (death, reinfarction, stroke, revascularization procedures, new

heart failure, or pulmonary edema), and bleeding variables • The highest Integrilin dose groups had more complete reperfusion (TIMI

grade 3 flow, 66% versus 39% for placebo-treated patients; P=.006) • Shorter median time to ST-segment recovery (65 versus 116 minutes for

placebo; P=.05).• Mortality: 5.6% in integrin treated and 3.6% in placebo treated group• Death and re-infarction: 8% in integrin treated and 7.3% in placebo treated• The groups had similar rates of the composite end point (43% versus 42% for

placebo-treated patients) Circulation 1997;95

RAPPORTReoPro and Primary PTCA Organization and Randomization Trial

• The primary end point was death, reinfarction, or any (urgent or elective) target vessel revascularization (TVR) at 6 months

• abciximab significantly reduced the incidence of death, reinfarction, or

urgent TVR at all time points assessed: 9.9% versus 3.3%, at 7 days;

11.2% versus 5.8%, at 30 days; and 17.8% versus 11.6%, at 6 months The effect of abciximab with respect to death or reinfarction: 4.7% versus

1.4%, at 7 days; 5.8% versus 3.2%, at 30 days; and 12.0% versus 6.9%, at 6 months

Circulation 1998;98

TIMI-14 (Substudy)Thrombolysis in Myocardial Infarction-14

(alteplase, abciximab) alone or abciximab+ reduced dose of lytics • ST segment resolution: 59% in combination of tPA+ abciximab vs.

37% in full dose tPA alone• 30-day mortality: 1.1% with complete ST resolution 4.7% with incomplete ST resolution 7.1% with no ST resolution

Circulation 2000;101

ISAR-2Intracoronary Stenting and Antithrombotic Regimen-2

coronary stenting +/- abciximab

• 30-day MACE: 5% in abciximab and 10.5% in heparin groups• 30-day death: 2% in abciximab and 4.5% in heparin groups• 30-day MI: 0.5% in abciximab and 1.5% in heparin groups• 30-day TVR: 3% in abciximab and 5% in heparin groups• At one year there was 5.7% absolute reduction in cardiac events• At six-month restenosis: 31.1% in abciximab and 30.6% in heparin

groups

JACC 2000;35