STEMI – My Approach

2010

Dr S A MerchantInterventional Cardiologist

DM MD DNB FSCAI Lilavati, CritiCare, BSES, Breach Candy Hospitals

Clinical manifestations of arterial thrombosis

UA/NQMI:Partially-occlusive thrombus

(primarily platelets)

Intra-plaque thrombus (platelet

dominated)

Plaque core

ST MI:occlusive thrombus

(platelets, red blood cells, and fibrin)

Intra-plaque thrombus (platelet

dominated)

Plaque core

SUDDEN DEATH

Adapted from Davies MJ. Circulation. 1990; 82 (supl II): 30-46.

Dr S A Merchant

Initial Diagnosis of STEMI

Dr S A Merchant

Small, vulnerable plaques are responsible for causing MI

68%

18% 14%0

20

40

60

<50% 50%–70% >70%

% Stenosis

MI Patients

(%)

Falk et al: Circulation 1995;92:657–671 Dr S A Merchant

Pre CCU era CCU era Reperfusion era0

5

10

15

20

25

30

35

4030

15

6.5

% Mortality

Defibrillation,Hemodynamic

monitoringBeta Blockade Thrombolysis/

adjuct therapyPTCA, Stent

THE IMPACT OF MEDICAL THERAPY

MANAGEMENT OF Acute Myocardial Infarction

Dr S A Merchant

Transport of Patients With STEMI and Initial Reperfusion Treatment

J Am Coll Cardiol. 2004;44:671; Circulation. 2004;110:588.

EMS transport

Onset of symptoms of STEMI

9-1-1EMS

dispatch

EMS on scene• Encourage 12-lead ECGs• Consider prehospital

fibrinolytic if capable and EMS–to–needle within 30 minGOALS

PCIcapable

Not PCIcapable

Hospital fibrinolysis: Door–to–needle

≤ 30 min

EMS triage

plan

Inter-hospitaltransfer

“Golden Hour” = 1st 60 minTotal ischemic time: within 120 min

Patient EMS Prehospital fibrinolysisEMS–to–needle≤ 30 min

EMS transportEMS–to–balloon ≤ 90 min

Patient self-transport Hospital door–to–balloon

≤ 90 min

Dispatch

1 min

5 min

8 min

Boersma et al, Lancet 1996 348:771

Thrombolysis Versus Primary PCI - Time DependancyAbsolute 35 day mortality reduction v treatment delay

0 3 6 9 12 15 18 21 240

20

40

60

80

Treatment delay (h)

Ab

so

lute

be

ne

fit:

liv

es

s

av

ed

/1

00

0 p

ts t

rea

ted N=50246

Primary PCI

Dr S A Merchant

Primary PCI

angioplasty vs

thrombolysis

angioplasty vs

thrombolysis

Dr S A Merchant

PerCutaneous Interventions following AMI : A variety !!

Thrombolytic Therapy Prior to PCI

Successful reperfusion after Thrombolysis

Timing of PCI after Thrombolysis

Direct (Primary ,Emergency)

No Not Applicable Not Applicable

Rescue (Salvage)

Yes No 1.5 to 2 h

Facilitated (Immediate)

Yes +/- Immeterial Immediate

Early Yes Yes 12-48 h

Deferred (Elective)

Yes Yes >48 h

Dr S A Merchant

Primary PCI

POBA vs StentPOBA vs Stent

Dr S A Merchant

primary PTCA vs stentprimary PTCA vs stent

6-month outcomes6-month outcomes

00 0.50.5 1.51.511 22

OR (95% CI)OR (95% CI)stentstent

death

reMI

death/ reMI

TVR

death/reMI/TVR

death

reMI

death/ reMI

TVR

death/reMI/TVR

3.3%

1.7%

4.9%

8.3%

13.7%

3.3%

1.7%

4.9%

8.3%

13.7%

3.8%

3.0%

6.8%

18%

25.9%

3.8%

3.0%

6.8%

18%

25.9%

PTCAPTCA

stent betterstent better

PTCA betterPTCA better

0.85 (0.57-1.27)0.85 (0.57-1.27)

0.58 (0.35-0.96)0.58 (0.35-0.96)

0.72 (0.52-0.98)0.72 (0.52-0.98)

0.41 (0.32-0.52)0.41 (0.32-0.52)

0.45 (0.37-0.55)0.45 (0.37-0.55)

Dr S A Merchant

Real world situation: Door to balloon times in USA

N=365N Engl J Med 2006;355

Dr S A Merchant

Conclusion : Every minute delay in P’PCI affects 1 year mortality. Therefore, all efforts should be made to shorten Ischemia time not only for thrombolysis but also for P’PCI.

Door to Balloon minus

Door to Needle time

Anticipated delay between door to balloon minus door to needle time if more than one hour , then thrombolysis is a better strategy.

Assessment of time is the key point in the choice of reperfusion strategy

Dr S A Merchant

USIC 2000, French Registry Data Hospital administered ‘lysis as good as PCI

EURO-PCR Paris 2003

Pre hospital lysis

Dr S A Merchant

French USIC 2000 survey: real world

No reperfusio

n

Pre-hosp TT

Hosp TT

Primary PCI

Patients 386 (30%)

155 (12%)

322 (25%)

425 (33%)

Age (year)

71 60 61 61

Time to admission (h)

2.8 2.4 2.2 2.1

1 year death

14.7% 3.2% 9.0% 7.9%

USIC. Circulation 2004;110:1909-1915

Dr S A Merchant

Fibrinolysis vs Transfer for PCI

Pre Hosp Primary In Hosp Lysis PCI

Lysis

CAPTIM CAPTIM DANAMI 2 DANAMI 2

Death (%) 3.8 4.8 6.6 7.6

1yr 5.4 7.3

Reinfarction (%) 3.7 1.7 1.6 6.3

Disabling CVA (%) 1.0 0.0 1.12.0

Any of Above (%) 8.2 6.2 8.0 13.7*(* P < 0.003)

Vahanian ESC, 2002

Dr S A Merchant

Pre Hospital thrombolysisCAPTIM 1 Year Results (TNK)

Series10%

5%

2.2%

5.7%

Pre HospitalLysis

Pre HospitalLysis

PrimaryPCI

PrimaryPCI

P=0.057P=0.057DeathDeath

GW Symposium, AHA 2002GW Symposium, AHA 2002

Sx < 2 hours

Dr S A Merchant

Blush Score : 30 D, M in AMI receiving fibrinolysis regardless of TIMI Grade flow in Epicardial Artery,

Myocardial perfusion by blush score predicts mortality

Gibson : Circulation 2000;101-125

Improved flows

Failed flows

Se-ries1

0

5

10

15

20

25

30

35

74.5

2.2

6

1 0

7 897 7

21

2 1

5

13

PTCA vs Fibrinolysis:Short Term Clinical Outcomes (23

RCTs)

PTCA

Fre

qu

en

cy

(%)

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

P=0.0002

P=0.0003 P<0.0001

P<0.0001

P<0.0001P=0.0004

P=0.032

P<0.0001

Death Death, no

SHOCKdata

ReMI Rec. Isch

Total Stroke

Hem. Stroke

Major Bleed

DeathMICVA

Fibrinolysis

N = 7739

Is timing an issue even for Primary PCI?

Dr S A Merchant

Survival Benefit by Time to Treatment with Lytics

Dr S A Merchant

Dr S A Merchant

door-to-balloon times in primary PCIdoor-to-balloon times in primary PCI

8%8%

21% 21%24%24%

17%17%

10%10%

20%20%

<60<60 60-9060-90 120-150120-15090-12090-120 150-180150-180 >180>18000

55

1010

1515

2020

% of patients% of patients

minminC.P. CANNON. JAMA 2000;283:2941-7C.P. CANNON. JAMA 2000;283:2941-7

NRMI-2 : 27080 consecutive patientsNRMI-2 : 27080 consecutive patients

Dr S A Merchant

Mortality by time to reperfusion with Primary PCINRMI-2 Registry (27,080)

C.P. CANNON. JAMA 2000;283:2941-7 Dr S A Merchant

Why is Primary PCI less time dependent than Lysis?

1) Lysis is less effective at restoring infarct artery patency as the clot ages

2) Myocardial salvage and infarct size after lytics are very sensitive to time to reperfusion

3) Cardiac rupture is more likely to occur as the time to lysis increases

Dr S A Merchant

Recommendations

When performed by experienced* operators/centers, PCI is the reperfusion strategy of choice for patients with AMI

PCI for AMI: door-to-balloon time < 2hrs (time window up to 12 hours accepted)

* operator: 75 PCI (any type) / year; center: 36 Primary PCI / year

Dr S A Merchant

After 12 hours???

BRAVE-2

Rationale: While thrombolysis has been shown to produce no benefit after 12 hours, no similar studies have looked at primary PCI in this group.

Study: 365 patients randomized to in an invasive arm or a conservative arm. The invasive group underwent angiography and then PCI if necessary, while the conservative group was treated with conventional medical therapy. The primary end point was infarct size determined by SPECT at five to 10 days.

Results: Infarct size (%LV) was significantly reduced in the invasive arm (8.0 vs 13%; p=0.002). No clinical differences.

Kastrati ACC 2005 Dr S A Merchant

• primary PCI • primary PCI

Role of PCI in the management of STEMIRole of PCI in the management of STEMI agendaagenda

• the challenges• the challengeshow to achieve optimal reperfusionhow to achieve optimal reperfusion

what to do with the occluded IRAwhat to do with the occluded IRA

replacing the function of death cellsreplacing the function of death cells

- angioplasty vs thrombolysis- angioplasty vs thrombolysis

- added benefit of stent placement- added benefit of stent placement- timing

- culprit vessel vs all vessel intervention- role of 2b/3a inhibitors

- timing

- culprit vessel vs all vessel intervention- role of 2b/3a inhibitors

• transfer, rescue and facilitated PCI• transfer, rescue and facilitated PCI

• primary PCI • primary PCI

Dr S A Merchant

Dr S A Merchant

culprit vessel vs all vessel intervention

The ACC/AHA guidelines on PCI give elective PCI of a non-infarct related artery at the time of AMI a class III recommendation with a C level of evidence.

Exception: in case of cardiogenic shock, systematic intervention in multiple vessels may be required to optimize reperfusion of the heart.

Dr S A Merchant

Role of GP 2b/3a inhibitors

Dr S A Merchant

26.1%

11.2%9.7%

14.6%

4.5% 5.8%2.0%

6.0%

0%

10%

20%

30%

EPIC RAPPORT Neumann ADMIRAL

Placebo GP IIb/IIIa

p = 0.06

p = 0.03

p = 0.03

p = 0.01

N: 64 483 200 3002082

N: 64 483 200 3002082

GP IIb/IIIa Inhibitors For Primary PCI—30-Day Death, (re)MI or Urgent Revascularization

6.8%4.5%

CADILLAC

p = 0.02

Types of Thrombolytics

A. Clot Selective / Clot-Binding / fibrin Specific

B. Non clot Selective/ Non–Clot-Binding / Non Fibrin Specific

Dr S A Merchant

Action of Non–Clot-Binding AgentsAction of Clot-Binding Agents

(Alteplase, Tenecteplase) (Urokinase, Streptokinase)

Clot-BindingPlasminogen

Activators

Clinical Relevance of Fibrin Affinity

Clot Blood Vessel Non–Clot-BindingPlasminogen

Activators

Clot Blood Vessel

Dr S A Merchant

Thrombolytic Agents

Fibrin-Specific Recombinant tissue

plasminogen activator (rt-PA) Mutants and Variants of

Tissue-type Plasminogen Activator TNK-rt-PA Reteplase Lanetoplase

Single-chain Urokinase-type Plasminogen Activator Recombinant pro-urokinase

(saruplase) Staphylokinase

Non-Fibrin-Specific Streptokinase Anisoylated

Plasminogen Streptokinase Activator Complex

Dr S A Merchant

Overview of Thrombolytics

SK TNK t-PA r-PA

Molecular Wt 45,000 65,000 65,000 39,000

Fibrin specificity - ++++ ++ +

Plasma Half life (min)

~20 20 4-6 11-14

Speed of admistration

++ ++++ ++ +++

Systemic effect ++++ - + ++

Dose 1.5M unit iv infusion 30-60 min.

30-50 mg iv bolus

5-10 sec.

15mg bolus 50 mg 30m 35mg 60m

10mg +10mg iv double

bolus 30 min apart

Overview of Thrombolytics

SK TNK t-PA r-PA

PAI-1 resistance no Yes no no

Hypotensive effect

Yes no no no

Allergic effect Yes no no ?

Mortality Advantage

Inferior to t-PA

Equivalent to t-PA

Gold standard

Equivalent to SK

Trade Name Streptase Kabikinase

Metalyse Actilyse Rapilysin

Generic names streptokinase tenecteplase alteplase reteplase

Comparison with Streptokinase

Dr S A Merchant

Dr S A Merchant

Dr S A Merchant

Dr S A Merchant

rescue PCI

short term outcome: deathrescue PCI

short term outcome: death

Belenkie

RESCUE

PRAGUE

Vermeer

Belenkie

RESCUE

PRAGUE

Vermeer

n PCI cons.n PCI cons.

28

151

200

149

28

151

200

149

6.3%

5.1%

7%

8.7%

6.3%

5.1%

7%

8.7%

33.3%

9.6%

14.0%

6.7%

33.3%

9.6%

14.0%

6.7%

00 0.50.5 1.51.511 2.02.0

odds ratio (95% CI)odds ratio (95% CI)

0.13 (0.01-1.40)0.13 (0.01-1.40)

0.51 (0.12-2.06)0.51 (0.12-2.06)

0.46 (0.16-1.30)0.46 (0.16-1.30)

1.24 (0.31-4.49)1.24 (0.31-4.49)

0.55 (0.30-1.01)0.55 (0.30-1.01)p=0.052p=0.052totaltotal 528528 6.7%6.7% 11.5%11.5%

Dr S A Merchant

Series10%

5%

10%

15%

20%

2.5%

4.9%

Pre HospitalLysisPre HospitalLysis

PrimaryPCIPrimaryPCI

P=0.09P=0.09Incidence of ShockIncidence of Shock

CAPTIM – Prehospital tPA vs 1°PCI1 Year Results

Bonnefoy Lancet 2002Bonnefoy Lancet 2002

Series10%

10%

5.4%

7.3%

P=0.27P=0.27Death at 1 YearDeath at 1 Year

Pre HospitalLysisPre HospitalLysis

PrimaryPCIPrimaryPCI

Dr S A Merchant

Tenecteplase is the lytic of choice

Cantor also emphasized that previous trials have used different lytics and no clopidogrel preloading.

"Streptokinase is not very cath-lab friendly, so

patients were more prone to getting bleeding complications when they went to the cath lab.

Those previous trials were also done before we knew the benefits of preloading patients with clopidogrel and using antithrombotic therapies like GP IIb/IIIa inhibitors during the angioplasty."

Dr S A Merchant

Dr S A Merchant

Death / Nonfatal MI / Nonfatal ICH

Death / Nonfatal MI / Nonfatal Major Bleed

Death / Nonfatal MI / Nonfatal Disabling Stroke

Enox Better UFH BetterRR

UFH (%) Enox (%) RRR (%)

12.3 10.1 18

12.8 11.0 14

12.2 10.1 17

ExTRACT TIMI 25Net Clinical Benefit at 30 Days

ExTRACT TIMI 25Net Clinical Benefit at 30 Days

Dr S A Merchant

CLARITY–TIMI 281° Endpoint: Occluded Artery (or D/MI Thru Angio/HD)

| | | | | |0.4 0.6 0.81.01.2 1.6

Odds ratio 0.64(95% CI, 0.53 – 0.76)

P < 0.001

Clopidogrel Placebobetter better

Series10

5

10

15

20

25

15.0

21.7

Clopidogrel PlaceboLD 300 mgMD 75 mg

Occlu

ded

art

ery

or

death

/MI

(%)

36% odds

reduction

n = 1,752 n = 1,739

Sabatine MS, N Engl J Med. 2005;352:1179-1189. Dr S A Merchant

Pro

port

ion

dead

befo

re fi

rst

dis

ch

arg

e (

%)

Time since randomization (days)

Placebo + ASA: 1,845 deaths (8.1%)

Clopidogrel + ASA:1,726 deaths (7.5%)

0.6% ARD7% RRR P = 0.03

COMMIT: Effect of Clopidogrel on Death Inhospital

N = 45,852 No age limit; 26% age ≥ 70

years

Lytic Rx 50%

No LD given

Chen ZM, et al. Lancet. 2005;366:1607-1621.

0 7 14 21 28

10

9

8

7

6

5

4

3

2

1

0

Dr S A Merchant

Summary

Acute therapy in STEMI focuses on reperfusion & antithrombotic therapy

Reasonable options for hospitals without onsite PCI capability

Fibrinolytic Therapy (goal : door to needle time ≤ 30 minutes)

Transfer for Primary PCI (goal: door to balloon time ≤ 90 minutes)

Transfer for Rescue PCI if reperfusion with lytic fails Facilitated PCI : no clinical benefit seen to date

Clopidogrel in combination with aspirin results in significant further improvements in outcomes of patients with STEMI (CLARITY-TIMI 28/COMMIT)

Dr S A Merchant

Current ACC/AHA STEMI guidelines recommend IV UFH as ancillary therapy to reperfusion therapy

Enoxaparin is superior to current standard of UFH as the antithrombin to support fibrinolysis (ExTARCT TIMI 25)

Enoxaparin has a beneficial effect in patients undergoing elective PCI,with no increase in bleeding (PCI - ExTARCT TIMI 25)

Fondaparinux is beneficial in STEMI without increasing the risk of bleeding or stroke (OASIS 6), but some subsets do not benefit (eg primary PCI)

Fondaparinux was not superior to UFH is Stratum 2 of OASIS 6 for STEMI

Long term treatment involves aggressive multifactorial lifestyle modification & both antithrombotic & anti ischemic therapies

Summary (cont.)

Dr S A Merchant

Complete obstruction

Partial flow

Full flow

Partial success with

pharmacologicreperfusion

Rethrombosis:Prevented by antiplatelet

and anticoagulant Rx

PCI p lyticIdeal goal of

pharmacologicreperfusion

Pharmacoinvasive approach

Dr S A Merchant

Fibrinolysis generally preferred Early presentation ( ≤ 3 hours from symptom onset and delay to invasive strategy)

Invasive strategy not an option Cath lab occupied or not available Vascular access difficulties

No access to skilled PCI lab

Delay to invasive strategy Prolonged transport

Door-to-balloon more than 90 minutes > 1 hour vs fibrinolysis (fibrin-specific agent)

now

ACC/AHA Guidelines for Management of Patients With STEMI, 2004 Reperfusion Options for STEMI Patients

If presentation is < 3 hours and there is no delay to an invasive strategy, there is no preference for either

strategy.

ACC/AHA Guidelines for Management of Patients With STEMI,Journal of the American College of Cardiology 2004 Dr S A Merchant

Emerging ModalitiesPharmacoinvasive Management

(PCI following TNK) is a better , safer option than PAMI as proved recently .

JACC Sept 2007

It widens the time window for PCI

This seems to combine the benefits of Mechanical and pharmacological strategies in reperfusion

Dr S A Merchant

When patients present to a primary unit without interventional capabilities:Therapeutic options

a) lyticsb) “transfer” to a facility with a cardiac cath lab

(with or without adjunctive therapy – “facilitated PCI”).

Any such “transfer” needs to be effected rapidly to take advantage of the early benefits of revascularization.

Dr S A Merchant

‘Best of both worlds’ :

Local rapid Thrombolysis to

majority

&

PCI Routinely

Dr S A Merchant

TRANSFER-AMI:

high-risk STEMI

Standard treatment after fibrinolysis (rescue PCI for failed reperfusion, with elective PCI encouraged for successfully reperfused patients after 24 hours)

Pharmacoinvasive strategy (transfer for PCI within six hours of fibrinolysis).

Both groups received Tenecteplase

Dr S A Merchant

TRANSFER-AMI: 30-Day Primary End Point and Components

Dr S A Merchant

TRANSFER-AMI:

STEMI to centers without timely access to a catheterization lab pharmacoinvasive approach consisting of full-dose thrombolytics, followed by emergent transfer for cardiac catheterization within 6 hours, is safe and efficacious compared to treatment with thrombolytics and transfer for rescue PCI only.

This suggests that transfer to PCI centers should be initiated immediately after fibrinolysis without waiting to see whether reperfusion is successful or not.

Dr S A Merchant

TRANSFER-AMI: 30-Day Bleeding End Points

Dr S A Merchant

direct stentingn 102

direct stentingn 102

angio end pointslow flow (TIMI 3 2)no-flow (TIMI 0-1)distal embolization

clinical outcomes (6-m F/U)deathre-MITVR

angio end pointslow flow (TIMI 3 2)no-flow (TIMI 0-1)distal embolization

clinical outcomes (6-m F/U)deathre-MITVR

direct stenting in acute MI direct stenting in acute MI

C. LOUBEYRE et al. JACC 2002;39:15-21C. LOUBEYRE et al. JACC 2002;39:15-21

11.7%

2.9%4.9%3.9%

0.9%2.9%8.8%

11.7%

2.9%4.9%3.9%

0.9%2.9%8.8%

pre-dilatationn 104

pre-dilatationn 10426.9

%

12.5%

7.6%6.7%

3.8%3.8%6.7%

26.9%

12.5%

7.6%6.7%

3.8%3.8%6.7%

p=0.01

p=0.02

p=0.01

p=0.02

angio end pointangio end point 11.7%

11.7%

26.9%

26.9%slow flow (TIMI 3 2)slow flow (TIMI 3 2) 2.9%2.9% 12.5%

12.5%

endovascular coolingendovascular cooling

SR DIXON. JACC 2002;40:1928-34SR DIXON. JACC 2002;40:1928-34 COOL-MI n 400 ptsCOOL-MI n 400 pts

% pts% pts

00MACEMACE

1010

0%0%

10%10%

median infarct sizemedian infarct size

2%2%

8%8%% LV% LV

55

00

1010

55

cooling n 21 cooling n 21 control n 21 control n 21

new cathether-based techniquesnew cathether-based techniques

thrombectomy

distal protection

thrombectomy

distal protection

mechanismmechanismCRTs in

AMICRTs in

AMIX-AMINE

AIMI

EMERALD

X-AMINE

AIMI

EMERALD

N 200N 200

N 500

PROMISE

N 200

N 500

PROMISE

N 200

devicedeviceX-SIZER•

ANGIOJET

EXPORT

CATHETER

PERCU-SURGE

FILTER-WIRE

X-SIZER•

ANGIOJET

EXPORT

CATHETER

PERCU-SURGE

FILTER-WIREDr S A Merchant

RECOMMENDATION

Task Force ESC 2005 guideline

Routine Coronary Angio & PCI, if applicable,

in successful Thrombolysis: 1 A

LYSE NOW, STENT LATER !!

Dr S A Merchant

Despite the clinical superiority of PAMI, thrombolytic therapy is the default treatment in many countries due to the practical

limitations of PAMI

Dr S A Merchant

Conclusion

In Indian context – Thrombolysis is the commonly accepted method of treatment in STEMI

PCI is superior as per data but not practical and feasible, not only in India but also all over world

Dr S A Merchant

New TNK is an ideal , novel thrombolytic agent, IV bolus reduces door to needle time and higher TIMI III and II flow( 86%)

New emerging post fibrinolysis PCI has emerged as an alternative method of treatment that appears to be safer &better as compared to PAMI

Dr S A Merchant

API Guidelines

Indications for thrombolytic therapy

Early presentation (3 h or less from symptom onset and delay to invasive strategy)

Invasive strategy is not an option- Catheterization laboratory not available / occupied.

- Financial reasons

- Lack of access to a skilled PCI laboratory

- Vascular access difficulties Delay to invasive strategy

Prolonged transport (Door-to-Balloon)- (Door-to-Needle) time > 1 hour.

Medical contact-to-balloon or door-to-balloon time > 90 minutes

Dr S A Merchant

ELAXIM INDIAN REGISTRY

Series160

65

70

75

80

85

9086.71

89.1485.06

73.88

% Clinically Successful Thrombolysis

overall <3hrs 3-6hrs >6hrs

Dr S A Merchant

ELAXIM INDIAN REGISTRY

Adverse events reportedIndian Registry ASSENT-2

Any bleeding (excluding ICH*) 4.62% 21.76%

ICH (without GpIIb/IIIa inhibitors) 0.48% 0.93%

Stroke (Non-ICH) 0.24% 1.78%

Myocardial re-infarction 3.33% 4.10%

Ventricular arrhythmias 5.71% 20.5%

Mortality (All cause) 3.48% 6.18%

* ICH = Intracranial hemorrhage Dr S A Merchant

2.5%

4.9%

0%

5%

10%

15%

20%

Pre HospitalLysisPre HospitalLysis

PrimaryPCIPrimaryPCI

P=0.09P=0.09Incidence of ShockIncidence of Shock

CAPTIM – Prehospital tPA vs 1°PCI

1 Year Results

Bonnefoy Lancet 2002Bonnefoy Lancet 2002

5.4%

7.3%

0%

10%P=0.27P=0.27

Death at 1 YearDeath at 1 Year

Pre HospitalLysisPre HospitalLysis

PrimaryPCIPrimaryPCI

Dr S A Merchant

TIMI 0 Complete occlusion

TIMI 1 Penetration of obstruction by contrast but no distal perfusion

TIMI 2 Perfusion of entire artery

but delayed flow

TIMI 3 Full perfusion, normal flow

10.6

7

4.7

0

2

4

6

8

10

12

14

TIMI 0/1 TIMI 2 TIMI 3

Mortality at 42 Days

P < 0.005

TIMI 1

OPEN ARTERY THEORY:Better flow in the infarct artery improves survival

Chesebro JH et al. Circulation 1987;76:142-54

Full-Dose TNK 3-12h Before PCI: GRACIA-2

Characteristic TNK+PCI PCINo. patients 103 102TIMI flow grade 3 59%* 43%Complete STRes (6h) 61%* 43%Death, MI, RI-UR 9% 12%Major bleeding 2% 3%

No differences in infarct size, LV function*p < 0.05

Aviles ESC 2003Aviles ESC 2003 Dr S A Merchant

Occluded Artery Trial (OAT)Occluded Artery Trial (OAT)

1º endpoint: death/reMI/rehosp. CHF (NYA class IV) over 3 years1º endpoint: death/reMI/rehosp. CHF (NYA class IV) over 3 years

multicenter, randomized, controledmulticenter, randomized, controled

randomizationrandomization

n 3200 patientsoccluded IRA (TIMI 0,1) n 3200 patientsoccluded IRA (TIMI 0,1)

PCI (3-28 days after MI) + risk factor modificationPCI (3-28 days after MI) + risk factor modification

no PCIno PCI

ASA-blockersACE inhibitors

ASA-blockersACE inhibitors

Apoptotic Rate in Occlued vs Open IRA

Abbate A et al. Circulation 2002

• hazards of stem cell manipulation

• arrhythmogenic potential of implanted cells

• hazards of stem cell manipulation

• arrhythmogenic potential of implanted cells

open questions on infarct/necrotic tissue

open questions on infarct/necrotic tissue

• economic issues• economic issues

• the capacity of the stem cells to find their

optimal myocardial ‘niche’

• the capacity of the stem cells to find their

optimal myocardial ‘niche’

• long-term fate of transplanted cells in the

recipient heart

• long-term fate of transplanted cells in the

recipient heart

• optimal timing for transplantation• optimal timing for transplantationDr S A Merchant

Take Home Message:

Optimum management of STEMI – A PharmacoInvasive Approach

Initial Fibrinolysis with t-PA within 30-60 mins of chest pain in ambulance, nursing home, non-PCI hospital

Endovascular cooling: Aspirin, loading dose clopidogril/prasugrel, Inj Enoxyparin, GpIIb/IIIa Inhibitor, nitrates, Ace-Inhibitors, beta blocker, diltiazem, high dose statins, trimatazione, sedation

Dr S A Merchant

Transfer patient within 6 hours to PCI centre for

Cor angiography

Thrombectomy: Suction by Export Cath, AngioJet

Direct stenting

Intracoro NTG/Nicorandil

This makes sense to everyone – patient, relations, family doctor, consultant physician, interventional cardiologist. Also, both short term & long term clinical trials show excellent result with pharmacoinvasive approach in terms of reduce mortality, re-infarction & overall preservation of LV function

Dr S A Merchant

Rescue PCI, Cardiogenic shock PCI, Facilitated

PCI, Elective PCI are special

subsets where clinician

discretion is required

Dr S A Merchant

LONG DIFFUSE STENOSIS

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