Thrombolysis vs primary pci

Dr. Καζινάκης ΓεώργιοςΔιευθυντής ΕΣΥ

Α’ πανεπιστημιακή Καρδιολογική κλινική ΑΠΘ ΑΧΕΠΑ

2

Epidemiology of CHD in the US• Single most frequent cause of death

– 656,000 deaths in 2002

– 1 of every 5 deaths

• Incidence– Each year, 1.2 million Americans will have a new or recurrent

coronary event, and >40% will die as a result

– 700,000 events will be first attacks; 500,000 will be recurrences

• Prevalence– 13 million Americans have a history of CHD

(acute MI, other acute ischemic (coronary) heart disease, angina pectoris, atherosclerotic cardiovascular disease, and all other forms of heart disease)

CHD = coronary heart disease; MI = myocardial infarction.American Heart Association. Heart Disease and Stroke Statistics—2005 Update; 2005.

4

ACUTE CORONARY SYNDROMES

No ST elevation ST elevationUnstable

anginaNSTEMI STEMI

CAD Spectrum

Stableangina

Source (Photos): Davies MJ. Heart. 2000;83:361-366.

CAD = coronary artery disease; NSTEMI = non-ST-segment elevation myocardial infarction;STEMI = ST-segment-elevation myocardial infarction.

16,5 16,7

10,8

8.0 7,66,8

5,4

8,3

0

2

4

6

8

10

12

14

16

18

20

Death Death - present

<3 hrs

Death - present

>3 hrs

Death, reMI,

stroke

30

-Da

y E

ve

nts

(%

)

SK

Transport/PCI

PRAGUE 1+2: SK vs. transport (n=1250)

9,5%

7.2%

1,9%

15,8%

2,3%

7.3%

2,2%

0%1,1%

9,1%

0%

5%

10%

15%

20%

Death Reinfarction Hemorrhagic

stroke

Total stroke Death, reMI or

stroke

Even

t ra

te

Lysis PCI

5 RCTs of Lysis vs. Transport for PCI

Longest follow-up data used. Keeley, Grines. Lancet 2003;361:13-20

N = 2,909

P=0.25 P<0.05

P<0.0001

P<0.0001P=0.057

Average transfer time 39 mins

9,3%

7,4%6,8%7,0%

5,3%

2,5%

0%

2%

4%

6%

8%

10%

12%

Death Death (excl shock) Reinfarction

Even

t ra

te

Lysis PCI

23 Randomized Trials of PCI vs. Lysis

p=0.0002 p=0.0003 p<0.0001

N = 7,739

Keeley, Grines. Lancet 2003;361:13-20

23 Randomized Trials of PCI vs. Lysis

N = 7,739

Keeley, Grines. Lancet 2003;361:13-20

1,1%

2,2%

0.08%

1,0%

0%

1%

2%

3%

Hemorrhagic stroke Total stroke

Even

t ra

te

Lysis PCI

P<0.0001

p=0.0002

Zahn, et al. JACC 2001;37:1827-35

thrombolysis betterprimary angioplasty better

10.80.60.40.20 1.2 1.4 1.6

Adjusted mortality odds ratios with 95% CI

ALL

no heart failure on ad.heart failure on ad.

no diagnostic ECGdiagnostic ECG

no prior MIprior MI

no cardiogenic shockcardiogenic shock

resuscitationno resuscitation

malefemale

posterior MIanterior MI

age<75 yearsage75 years

Prospective registries RIKS - HIA

Prospective registries RIKS - HIA

• 26 205 consecutive patients from register of information and knowledge of swedishheart intensive care admissions.

• 16043 inpatient thrombolysis; 3078 patients prehospital thrombolysis and 7084 patients PCI.

• Up to 1 year of follow up.

Prospective registries RIKS - HIA

Prospective registries

28

32

Interhospital Transfer for PCIM

ort

alit

y(%

)

(n=200)Czech

(n=137)RO MI

(n=850) Czech

(n=1129)DK

(n=150)ND

6.7

1412.1

8.57

8.46.8 6.5

10

6.7

0

5

10

15

20

LIMI PRAGUE-1 AIR-PAMI PRAGUE-2 DANAMI

On-site Fibrinolysis Transfer for PCI

Vermeer F. Heart 1999;82:426

Widimsky P. Eur Heart J 2000;21:823

Widimsky P. Eur Heart J 2003;24:94

Andersen HR. N Engl J Med 2003;349:733

Grines CL. J Am Coll Cardiol. 2002;39:1713

33

5,9%

2,2%

3,7%

5,7%

0%

2%

4%

6%

8%

10%

<2 Hrs

(n=460)

>2 Hrs

(n=374)

30-d

ay m

ort

ali

ty

Pre-hosp tPA

PCI

7,4%

15,3%

7,3%6,0%

0%

5%

10%

15%

20%

<3 Hrs

(n=551)

>3 Hrs

(n=299)

30-d

ay m

ort

ali

ty

Lytic (SK)

Transfer for PCI

Early Presenting Patients: Primary PCI v Fibrinolytics

p=0.058 p=0.47

CAPTIM

p<0.02

PRAGUE-2

Widimsky P, et al. Eur Heart J. 2003;24(1):94-104. Steg PG, et al. Circulation. 2003;108(23):2851-2856.

ppci

Fibrinolytic therapy

cardiac arrest - resuscitation

unresolved problems in the treatment of STEMI patients

• improving appropriate and timely diagnosis of STEMI by medical and paramedical-run emergency units,

• the efficiency of network models in urban and non-urban areas,

• the best approach to late presenters, • prevention and treatment of the no-reflow

phenomenon and reperfusion injury, • the potential benefit of bioabsorbable stent platforms

in this setting, • and prevention of left ventricular remodelling or • the potential benefits of regenerative therapies.

unresolved problems in the treatment of STEMI patients

• Aspiration thrombectomy in ST-elevation myocardial infarction

• Primary PCI: time to change focus from epicardial reperfusion towards protection of the microvasculature

• Multivessel PCI in STEMI: ready to be the recommended strategy?

• Fractional flow reserve and the index of microvascular resistance in patients with acute coronary syndromes

• The conundrum of antithrombotic drugs before, during and after primary PCI

• Shock management in acute myocardial infarction

• A review of the role of nurses and technicians in ST-elevation myocardial infarction (STEMI)

unresolved problems in the treatment of STEMI patients

• Research in these and other fields will lead to further improvement of short- and long-term outcome of STEMI patients.

STREAMSTRATEGIC REPERFUSION EARLY AFTER MYOCARDIAL INFARCTION

A strategy of early fibrinolysis followed by coronary angiography within 6-24 hours or rescue PCI if needed was compared with

standard primary PCI in

STEMI patients with at least 2 mm ST-elevation in 2 contiguous leads presenting within 3 hours of symptom onset and unable to

undergo primary PCI within 1 hour.

STUDY AIM

no lytic

STUDY PROTOCOL

RANDOMIZATION 1:1 by IVRS, OPEN LABEL

Am

bu

lan

ce

/ER

Primary endpoint: composite of all cause death or shock or CHF or reinfarction up to day 30

ECG at 90 min: ST resolution ≥ 50%

Standard primary PCI

Aspirin

Clopidogrel:

LD 300 mg + 75 mg QD

Enoxaparin:

30 mg IV + 1 mg/kg SC

Q12h

Antiplatelet and

antithrombin treatment

according to local standards

angio >6 to 24 hrs

PCI/CABG if indicated immediate angio +

rescue PCI if indicated

YE

S

N

O

Strategy A: pharmaco-invasive Strategy B: primary PCI

Aspirin

Clopidogrel:

75 mg QD

Enoxaparin:

0.75 mg/kg SC Q12h

PC

I H

os

pit

al

STEMI <3 hrs from onset symptoms, PPCI <60 min not possible, 2 mm ST-elevation in 2

leads

≥75y: ½ dose TNK<75y:full dose After 20% of the planned recruitment,

the TNK dose was reduced by 50% among

patients ≥75 years of age.

62

Sx onset

1st Medicalcontact

61

1 Hour 2 Hoursn=1892

29

Randomize IVRS

9

Rx TNK

31 86

Sx onsetRx PPCI

100 min

178 min

MEDIAN TIMES TO TREATMENT (min)

1st Medicalcontact

78 min differenceRandomize IVRS

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

0 1 2 3 0 1 2 3

PATI

ENTS

Pharmaco-invasive(N=944)

PPCI(N=948)

TIMI FLOW RATES

TIMI before PCI TIMI after PCI

P<0.001 P=0.41

SINGLE ENDPOINTS UP TO 30 DAYS

Pharmaco-invasive

(N=944)

PPCI

(N=948)

P-value

All cause death

Cardiac death

(43/939) 4.6%

(31/939) 3.3%

(42/946)

4.4%

(32/946)

3.4%

0.88

0.92

Congestive heart

failure

(57/939) 6.1% (72/943)

7.6%

0.18

Cardiogenic shock (41/939) 4.4% (56/944)

5.9%

0.13

Reinfarction (23/938) 2.5% (21/944)

2.2%

0.74

STROKE RATES

Pharmaco-invasive PPCI P-value

TOTAL POPULATION (N=1892)

Total stroke

fatal stroke

Haemorrhagic stroke

fatal haemorrhagic stroke

15/939 (1.60%)

7/939 (0.75%)

9/939 (0.96%)

6/939 (0.64%)

5/946 (0.53%)

4/946 (0.42%)

2/946 (0.21%)

2/946 (0.21%)

0.03

0.39

0.04

0.18

POST AMENDMENT POPULATION (N=1503)

Total stroke

fatal stroke

Haemorrhagic stroke

fatal haemorrhagic stroke

9/747 (1.20%)

3/747 (0.40%)

4/747 (0.54%)

2/747 (0.27%)

5/756 (0.66%)

4/756 (0.53%)

2/756 (0.26%)

2/756 (0.26%)

0.30

>0.999

0.45

>0.999

IN-HOSPITAL BLEEDING COMPLICATIONS

Pharmaco-invasive(N=944)

PPCI(N=948)

P-value

Major non-ICH

bleeding

6.5% 4.8% 0.11

Minor non-ICH

bleeding

21.8% 20.2% 0.40

Blood transfusions 2.9% 2.3% 0.47

My opponent has a tendency to

overestimate size!(and treatment

effect)

Treatment: The choice is yours

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