DR. RAJAT GANDHI, INTERVENTIONAL CARDIOLOGIST ,

BANKERS HEART INSTITUTE , VADODRA .

PRIMARY ANGIOPLASTY

HYPERTENSIONDIABETES MELLUTUS SMOKING OBESITY LACK OF EXERCISE DYSLIPIDAEMIA

RISK FACTORS FOR CAD

CORONARY ARTERY DISEASE

NON- ST ELEVATION

MI AND UNSTABLE

ANGINA

ST -ELEVATION

MISTABLE ANGINA

STABLE ANGINA - Chest discomfort precipitated by physical exertion releived by rest or nitrates .

UNSTABLE ANGINA -occurs at rest, last for more than 20 min, severe pain .

NSTEMI – evidence of myocardial necrosis with high cardiac enzymes .

STEMI - Complete occlusion of one coronary artery .

CORONARY ARTERY DISEASE

-sudden onset of retrosternal CHEST PAIN.-lasting for more then 30 min .-associated with nausea,vomiting, shortness of

breath

SYMPTOMS OF ACS

APPROACH TO THE PATIENT WITH ST – ELEVATION MI

Needle30 m ins

Balloon90-120 m ins

Door

Contac t

Call

Symptom s

TIME

ASPIRIN 150 MG CLOPIDOGREL /PRASUGREL/TICAGRELOR.STATIN (ATORVA -80MG,ROSUVA – 40 MG)NITRATES(IF HAEMODYNAMICALLY

STABLE)OXYGEN

GENERAL TREATMENT MEASURES

AGE >75 YRS SBP<100MMHG HEART RATE >100/MINLBBBH/O DM/HTNAWMITIME TO TREATMENT >4HRS

TIMI RISK SCORE FOR STEMI

Streptokinase - 1.5 MU in 30 – 60 min , allergic reactions, marked fibrinogen depletion , 50 % -90min patency rate ,

Tenectplase – 30-50 mg bolus , no allergic reaction , 75 % - 90 min patency rate , minimal fibrinogen depletion.

Reteplase –10 u two bolus , 30 min apart , moderate fibrinogen depletion ,75% - 90 min patency rate .

Alteplase – up to 100 mg in 90 min , mild fibrinogen depletion , 75% - 90 min patency rate .

FIBRINOLYTICS

ACTION OF FIBRINOLYTICS

ABSOLUTE – PRIOR ICH , CEREBERAL VASCULAR AV MALFORMATIONS , ISCHEMIC STROKE WITHIN 3 MONTHS , SUSPECTED AORTIC DISSECTION , BLEEDING DISORDERS , INTRACRANIAL NEOPLASMS .

RELATIVE – SBP >180 , DBP > 110MMHG, PREGNANCY , RECENT INTERNAL BLEEDING , RECENT MAJOR SURGERY,ISCHEMIC STROKE MORE THAN 3 MONTHS .

CONTRAINDICATIONS FOR FIBROLYTIC USE IN STEMI

FATAL INTRACRANIAL HAEMORRAGE .INADEQUATE MYOCARDIAL REPERFUSION CARDIOGENIC SHOCK .MYOCARDIAL RUPTURE .ANTIBODY RESISTANCE TO

STREPTOKINASE .

COMPLICATIONS OF FIBRINOLYTICS

ACC 2013 GUIDELINES FOR FIBRINOLYTIC THERAPY IN ACS PATIENTS .

In the absence of contraindications, fibrinolytic therapy should be given to patients with STEMI and onset of ischemic symptoms within the previous 12 hours when it is anticipated that primary PCI cannot be performed Within 120 min. In the absence of contraindications and when PCI is not available, fibrinolytic therapy is reasonable for patients with STEMI if there is clinical and/or ECG evidence of ongoing ischemia within 12 to 24 hours of symptom onset and a large area of myocardium at risk or hemodynamic instability.Fibrinolytic therapy should not be administered to patients with ST depression except when a true posterior (inferobasal) MI is suspected or when associated with ST elevation in lead aVR.

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Harm

PRIMARY ANGIOPLASTY – EMERGENCY PERCUTANEOUS CORONARY INTERVENTION (PCI) IN PATIENTS WITH ACUTE ST ELEVATION MYOCARDIAL INFARCTION PRESENTED WITHIN 12 HOURS OF ONSET OF SYMPTOMS .

RESCUE ANGIOPLASTY – PCI IN PATIENTS WITH FAILED THROMBOLYSIS .

FACILITATED ANGIOPLASTY –PCI IN PATIENTS WITH STEMI WHO ARE PRETREATED WITH GP IIBIIIA INHIBITORS OR FIBRINOLYTICS .

CORONARY ANGIOPLASTY

ACC 2013 GUIDELINES FOR PRIMARY PCI IN STEMI.

I IIaIIbIIIPrimary PCI should be performed in patients with STEMI and ischemic symptoms of less than 12 hours’ duration.

Primary PCI should be performed in patients with STEMI and ischemic symptoms of less than 12 hours’ duration who have contraindications to fibrinolytic therapy, irrespective of the time delay from FMC.

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Primary PCI should be performed in patients with STEMI and cardiogenic shock or acute severe HF, irrespective of time delay from MI onset.

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ACC GUIDELINES 2013 FOR PRIMARY PCI in STEMI

Primary PCI is reasonable in patients with STEMI if there is clinical and/or ECG evidence of ongoing ischemia between 12 and 24 hours after symptom onset.

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PCI should not be performed in a noninfarct artery at the time of primary PCI in patients with STEMI who are hemodynamically stable

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Harm

Antiplatelet Therapy to Support Primary PCI for STEMI

A loading dose of a P2Y12 receptor inhibitor should be given as early as possible or at time of primary PCI to patients with STEMI. Options include: • Clopidogrel 600 mg; or

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• Prasugrel 60 mg; or

• Ticagrelor 180 mg

Antiplatelet Therapy to Support Primary PCI for STEMI

Aspirin 150 to 300 mg should be given before primary PCI.

After PCI, aspirin should be continued indefinitely.

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Antiplatelet Therapy to Support Primary PCI for STEMI

P2Y12 inhibitor therapy should be given for 1 year to patients with STEMI who receive a stent (BMS or DES) during primary PCI using the following maintenance doses:• Clopidogrel 75 mg daily; or

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• Prasugrel 10 mg daily; or

• Ticagrelor 90 mg twice a day*

*The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg daily.

Antiplatelet Therapy to Support Primary PCI for STEMI

Prasugrel should not be administered to patients with a history of prior stroke or transient ischemic attack.

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New Inhibitors of the platelet the ADP P2Y12 receptor

Receptor Binding

Prodrug (requires hepatic activation)

Onset of Action

Half life

Clopidogrel Irreversible Yes Slow Long

Prasugrel Irreversible (stronger)

Yes More rapid Long

Ticagrelor Reversible (stronger)

No Rapid Short

Wallentin L et al. N Engl J Med 2009

PLATO: ticagrelor vs clopidogrel in ACS(n=18624)

Reduced risk of CV events with no increase in bleeding risk

NEWER ANTIPLATELETS PRASUGREL – risk of stent thrombosis is half

compared to clopidogrel , side effects ; high risk of bleeding in patients

with weight <60 kg and age > 75 . TICAGRELOR - reversible platelet inhibitor ,

safely given in patient with no restriction in age and weight .

Use of Stents in Patients With STEMI

Reperfusion at a PCI-Capable Hospital

Use of Stents in Patients With STEMI

Placement of a stent (BMS or DES) is useful in primary PCI for patients with STEMI.

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BMS* should be used in patients with high bleeding risk, inability to comply with 1 year of DAPT, or anticipated invasive or surgical procedures in the next year.

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DES should not be used in primary PCI for patients with STEMI who are unable to tolerate or comply with a prolonged course of DAPT because of the increased risk of stent thrombosis with premature discontinuation of one or both agents.

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*Balloon angioplasty without stent placement may be used in selected patients.

Harm

Closed Open artery

Arrival After balloon

Balloon

PRIMARY ANGIOPLASTY

PRIMARY ANGIOPASTY

PCI IN STEMI PATIENTS

Kastrati A et al. Eur Heart J 2007;28:2706-2713

DES vs BMS for primary PCI: meta-analysis of RCTs (n=2786)

HR: 0.38 (0.29-0.50)HR: 0.80 (0.48-1.39)

BARE METAL STENT BMS currently used in 10% to 20 %

patients .Large size vessel > 4.0 mm in diameter .Restenosis is higher in small size vessel ,long

lesions and patients with diabetes .Used in patients where dual antiplatelets

cannot be given for longer time .

Made up of cobalt chromium .Coated with durable polymer and drug.Polymer helps sustained release of drug over

30 days.Drugs like sirolimus, paclitaxel, everolimus.Theses drugs are immunosuppressive and

antiproliferative which prevent intimal hyperplasia .

DRUG ELUTING STENTS

PCI IN NSTEMI PATIENTS

Trials of Invasive vs Conservative

O’Donoghue, M. et al. JAMA 2008;300:71-80

NSTEMI

Non-MI ACS

STEMI

Chest Pain ?cause

Days after presentation

Prob

abil

ity

of

dyin

g

0102030405060708090

100

03Q1

03Q2

03Q3

03Q4

04Q1

04Q2

04Q3

04Q4

05Q1

05Q2

05Q3

05Q4

Year and quarter

Trea

tmen

t rat

e (%

)

STEMI

NSTEMI

Trop -ve ACS

NSTEMI: don’t under-estimate itPrognosis: poor

Undertreated

NSTEMI -etiology and prognosisMyocyte necrosis – troponin levels Haemodynamic stress – bnp and nt probnp

levels Vascular damage – microalbuminurea Inflammation – hsCRPAcclerated athersclerosis HBA1C LEVELS

AGE >70 YRS LBBBINCREASED TROPONIN LEVELS .INCRRASED CREATININE ,HBA1C,BNP

LEVELS HYPOTENSION HEART FAILURE

CLINICAL INDICATORS OF HIGH RISK IN NSTEMI .

Anticoagulant Therapy to Support Primary PCI

For patients with STEMI undergoing primary PCI, the following supportive anticoagulant regimens are recommended:

• UFH, with additional boluses administered as needed to maintain therapeutic activated clotting time levels, taking into account whether a GP IIb/IIIa receptor antagonist has been administered; or

• Bivalirudin with or without prior treatment with UFH.

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Antiplatelet Therapy to Support Primary PCI for STEMI

It is reasonable to start treatment with an intravenous GP IIb/IIIa receptor antagonist at the time of primary PCI (with or without stenting or clopidogrel pretreatment) in selected patients with STEMI who are receiving UFH.

• Double-bolus eptifibatide: 180 mcg/kg IV bolus, then 2 mcg/kg/min; a 2nd 180-mcg/kg bolus is administered 10 min after the 1st bolus.

• Abciximab: 0.25 mg/kg IV bolus, then 0.125 mcg/kg/min (maximum 10 mcg/min); or

• High-bolus-dose tirofiban: 25 mcg/kg IV bolus, then 0.15 mcg/kg/min; or

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CABG in Patients With STEMI

Urgent CABG is indicated in patients with STEMI with severe LMCA DISEASE .

CABG is recommended in patients with STEMI at time of operative repair of mechanical defects.

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Transfer of Patients With STEMI to a PCI-Capable Hospital for Coronary Angiography After Fibrinolytic Therapy

Transfer to a PCI-capable hospital for coronary angiography is reasonable for patients with STEMI who have received fibrinolytic therapy even when hemodynamically stable* and with clinical evidence of successful reperfusion. Angiography can be performed as soon as logistically feasible at the receiving hospital, and ideally within 24 hours, but should not be performed within the first 2 to 3 hours after administration of fibrinolytic therapy.

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*Although individual circumstances will vary, clinical stability is defined by the absence of low output, hypotension, persistent tachycardia, apparent shock, high-grade ventricular or symptomatic supraventricular tachyarrhythmias, and spontaneous recurrent ischemia.

Transfer of Patients With STEMI to a PCI-Capable Hospital for Coronary Angiography After Fibrinolytic Therapy

Immediate transfer to a PCI-capable hospital for coronary angiography is recommended for suitable patients with STEMI who develop cardiogenic shock or acute severe HF, irrespective of the time delay from MI onset. Urgent transfer to a PCI-capable hospital for coronary angiography is reasonable for patients with STEMI who demonstrate evidence of failed reperfusion or reocclusion after fibrinolytic therapy.

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Importance of Time to Reperfusion

Reinfarction

Microvascular Reperfusion

Myocardial Salvage

“Time is Muscle”

Series1-1

0

1

2

3

4

5

Impr

ovem

ent L

VE

F %

(7 m

os)

-0.2%

2.5%

4.8%

Brodie ACC 2003

Improvement in LV Ejection Fractionby Time to Reperfusion

p=0.03

<3 3-6 >6

Time to Reperfusion (hrs)

Myocardial Salvage by Time to Reperfusion with Primary PCI

<2 2-4 4-60

20

40

60

80

10080%

47% 44%

Time to Reperfusion

Myo

card

ial S

alva

ge In

dex

%

O’keefe J Nucl Cardiol 1995;2:35

0

1

2

3

4

CADILLAC(One Year)

Stent PAMI(6 Months)

Re-

infa

rctio

n %

1.5%

2.6%

3.3%

1.4%

0%

4.2%

3.0%p=0.003

p=0.03

Time to Reperfusion and Re-infarction

<3 3-6 >6 <2 2-4 4-6 >6

Time to Reperfusion (hrs)

Brodie AJC 2001;88:1085 Brodie ACC 2003

0

1

2

3

4

5

6

One

Yea

r M

orta

lity

%

<2 hrsTime To Presentation

1.9%

p=0.12

3.9%

5.1% 4.8%p=NS

Brodie ACC 2003

DB Time < 1.5 hrsDB Time > 1.5 hrs

CADILLAC Trial

>2 hrs

Door-to-Balloon Time and One Year Mortality Stratified by Time to Presentation

Door-to-Balloon Time and In-Hospital MortalityNRMI-2 Registry

0.6

0.8

1

1.2

1.4

1.6

1.8

2

2.2

Adj

uste

d O

dds R

atio

<1.0 1.0-1.5 1.5-2.0 2.0-2.5 2.5-3.0 >3.0

Cannon JAMA 2000;283:2941

Door-to-Balloon Time (hrs)

(n=27,080)

1.14 1.15

1.41

1.62 1.61

Death at 3 years – presentation delay

Maeng,M et al. Am J Cardiol 2010;105:1528 –1534)

Time to Reperfusion and One Year MortalityCADILLAC Trial (n=2002)

0

1

2

3

4

5

<2 2-3 3-4 4-6 6-12(n=121) (n=438) (n=455) (n=475) (n=513)

Time to Reperfusion (hrs)

One

Yea

r M

orta

lity

%

2.6 2.6

4.2 4.44.8

p=0.04(<3 hrs vs >3 hrs)

Brodie JAAC 2003

COMPARISON BETWEEN PRIMARY PCI AND THROMBOLYSIS

PCI vs Fibrinolysis for STEMI:Short-Term Clinical Outcomes

75

2

6

1

7 897 7

21

2 1

5

13

5

10

15

20

25

30

35 PCI

Freq

uenc

y (%

)

P=.0002P=.0003 P<.0001

P<.0001

P<.0001P=.0004

P=.032

P<.0001

Death Death, no shock

data

ReMI Rec.Ischemia

Total Stroke

Hem.Stroke

Major Bleed

DeathMI

CVA

Fibrinolysis N=7739

Keeley E, et al. Lancet . 2003;361:13-20.

Series10

2

4

6

8

10

12

14

16

DANAMI-2: 30 Day OutcomesLocal tPA vs Transport for Primary PCI

Death Re-infarction CVA MACE

Anderson NEJM 2003

Inci

denc

e %

8.5

6.5 6.2

1.9 2.0 1.6

14.2

8.5

tPAPCI (55 minute treatment delay)

p=0.002

(n=1129)

p<0.001

Results of trials examining post-procedural complications associated with PCI and thrombolysis

Lancet 2003;361:13–20.N Engl J Med 1999;341:1413–19N Engl J Med 1993;328:673–9.Eur Heart J 2007;28:679–84

Comparison of outcomes in ASSENT-4 with those in other trials of TNK in MI patients

End point ASSENT-2 (n=8461) (%)

ASSENT-3 (n=2038) (%)

ASSENT 3+ (n=821) (%)

ASSENT-4 TNK+PCI (n=829) (%)

ASSENT-4 PCI alone (n=836) (%)

30-day death 6.2 6.0 6.0 6.0 3.8

Intracranial hemorrhage

0.93 0.93 0.97 0.97 0

Total stroke 1.8 1.7 1.5 1.8 0Re-MI 4.1 4.2 5.8 5.2 2.7Major bleed 4.7 2.2 2.8 5.7 4.4

COMPARISON BETWEEN PRIMARY PCI AND FACILITATED PCI

1.03(0.15-7.13)

3.07(0.18-52.0)

1.43(1.01-2.02)

1.03

(0.49-2.17)

Mortality Reinfarction Major Bleeding

Fac. PCIBetter

PPCIBetter

Fac. PCIBetter

PPCIBetter

Fac. PCIBetter

PPCIBetter

Keeley E, et al. Lancet 2006;367:579.

0.1 1 10 0.1 1 10 0.1 1 10

1.38 (1.01-1.87)

1.71 (1.16 - 2.51)

1.51 (1.10 - 2.08 )

Lytic alone N=2953

IIb/IIIa alone N=1148

Lytic +IIb/IIIaN=399All (N=4500)

1.40 (0.49-3.98)

1.81 (1.19-2.77)

Systematic reviews

Individual studies – Gusto II B

0

2

4

6

8

10

12

14

16

18

0 5 10 15 20 25 30

10.6

16.6

Days from Randomization

% of Patients

Standard PCI > 24 hrs (n=496)Invasive < 6 hrs (n=508)

n=496n=508

422468

415466

415463

414461

414460

412457

Primary Endpoint: 30-Day Death, re-MI, CHF, Severe Recurrent Ischemia,

Shock

OR=0.537 (0.368, 0.783); p=0.0013

•PRIMARY PCI IS BETTER THAN THROMBOLYSIS.

•DEFINITE MORTALITY BENEFIT WITH PRIMARY PCI .

•COMPLICATIONS ARE LESS WITH PRIMARY PCI .

•PUBLIC AWARENESS IS REQUIRED TO EXPLAIN THE IMPORTANCE OF PRIMARY PCI .

•RESTORATION OF LV FUNCTION AND SALVAGE OF CARDIAC MUSCLE IS BEST WITH PRIMARY PCI .

SUMMARY

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