Conferencia magistral "20 años de Angioplastia Primaria para el tratamiento del Infarto. Experiencia y evolución de las redes de infarto" del Dr. Petr Widimsky durante la XXV Reunión Anual de la Sección de Hemodinámica y Cardiología Intervencionista (SHCI) de 2014 en Córdoba.

1. 20 years of Primary PCI for STEMI:
Czech experience and evolution of networks.
Petr Widimsky
Charles University Prague &
University Hospital Kralovske Vinohrady, Prague
Czech Republic

2. How to reperfuse the obstructed route ?
Before 1985: no routine treatment available
1986-1993: dissolving the clot (thrombolysis) in 25% of all STEMIs
1993-2002: reperfusion & revascularization (p-PCI) for 50% of STEMIs (locals only)
After 2002: reperfusion & revascularization (p-PCI) for all STEMIs (transport)

3. Geoff Hartzler (USA) 1982
1st primary PCI
Felix Zijlstra & Zwolle Group (NL) 1988-93
1st randomized trial on primary PCI
Otto Klein (CZ) 1929
1st diagnostic
cardiac catheterization Andreas Gruntzig (CH) 1977
1st PTCA

4. „1st Zwolle trial“ (NEJM 1993):
PCI superior to TL for patients directly admitted to PCI centers.
SK
(n=72)
P-PCI
(n=70)
p value
IRA recanalization 68% 91% 0,02
Discharge EF 45% 51% 0,004
Re-MI 13% 0% 0,003
Post-MI angina 19% 6% 0,001

5. 1990 cup of coffee in Rotterdam
1993-4 PCI training in Zwolle
1995 end of thrombolysis in Prague
1997-9 the PRAGUE-1 study
2002 Czech STEMI guidelines
2008 Stent for Life

6. Thrombolysis
(50% success rates
7% reocclusion risk)
Primary PCI
(90% success rates
3% reocclusion risk)
Modern therapy of AMI:
Thrombus removal,
Flow restoration

7. Reperfusion methods in STEMI:
Primary PCI:
•90% success rate
•8% death /re-MI /stroke
•3% reinfarctions
•1% strokes
•3-7% mortality in trials
•5-9% mortality in registries
Thrombolysis:
•50% success rate
•14% death /re-MI /stroke
•7% reinfarctions
•2% strokes
•6-9% mortality in trials
•10-17% mortality in registries

10. LIMI + PRAGUE-1
(Metaanalysis from: F. Vermeer, Heart 1999; 82:
426-31; P. Widimský, Eur Heart J 2000; 21: 823-31)
13
11
7
20
14
8
2
4
1
0
2
4
6
8
10
12
14
16
18
20
Mortality +/reMI Stroke
Thrombolysis
Both
PrimPTCA
%
N = 524

11. 0
2
4
6
8
10
12
ASSENT4 (2005) PRAGUE1 (1999)
Facilit.PCI
Prim.PCI
F. v/d Werf 2000: Routine transport of STEMI pts. to
PCI centers is not acceptable (EHJ 2000, editorial k PRAGUE)
F. v/d Werf 2006: ASSENT-4 (Lancet 2006; 367: 569–78)
 37%
 42%

12. PRAGUE-2: 30-days outcomes
Eur Heart J. 2003 Jan;24(1):94-104
10
6,80
15,2
8,4
0
2
4
6
8
10
12
14
16
Mortality +/re-MI/stroke
TL
PCI
P = 0,12
P < 0,003

13. Metaanalysis of 23 studies TL vs. PCI
(Keeley et al., Lancet 2003; 361: 13-20)
9
7 7
3
2
1
14
8
0
2
4
6
8
10
12
14
Mortality Re-MI Stroke Comb.end-
point
TL
PCI
% n=7739

14. Czech Republic:
Experience with primary PCI
and STEMI networks

15. Čas lék čes 1983; 122: 694-6.
Dec. 20, 1982

16. Real-life STEMI mortality in various hospital types
Czech Republic 1995
29
17 17
8
0
5
10
15
20
25
30
In-hospital mortality
No cardiologist on
duty
Cardiologist day-
hours
Cardiologist 24/7, but
no PCI
Cardiologist + PCI
24/7

17. Change of reperfusion strategy in University Hospital „Vinohrady“
Prague: October 5, 1995 thrombolysis declared non-lege artis
0
2
4
6
8
10
12
Mortalita STEMI
1994
1996

19. 5-leté přežívání po PCI
5-leté přežívání po trombolýze

20. STEMI guidelies of the Czech Society of Cardiology
PCIPCIPCIPain-ECG
3-12
hours
TLPCIPCIPain-ECG
< 3 hours
ECG-PCI
> 90 min.
ECG-PCI
30-90 min.
ECG-PCI
< 30 min.
STEMI
(Cor et Vasa 2002; 44: K123-143)

21. ….. The world first guidelines declaring p-
PCI as first treatment option !
• 2002 Czech Society of Cardiology
• 2003 European Society of Cardiology
• 2004 American College of Cardiology / AHA

22. Evolution of PCI rates in the Czech R.
320
1829
9270
16338
21676
22545
21624
0
5000
10000
15000
20000
25000
1990 1995 2000 2002 2004 2009 2013
PCI/rok/ČR
PCI/rok/ČR
PRAGUE-1
1999
PRAGUE-2
2002

23. P-PCI networks Czech Rep.

24. During 1999 – 2005 period the implementation of the „PRAGUE“ trials results
completely abolished mortality differences between hospital types
8
18
0
5
10
15
20
In-hospital mortality
Tertiary PCI centers Hospitals without cath-lab
6,8 6,9
0
5
10
15
20
In-hospital mortality
Tertiary PCI centers Hospitals without cath-lab

25. Stent for Life

27. ≥600 p-PCI / million / year
400-599 p-PCI / million / year
200-399 p-PCI / million / year
<200 p-PCI / million / year
Data not known
Annual Incidence of Primary PCIs

28. SFL prokázal, že národní strategie léčby infarktu trombolýzou vede k
tomu, že 46% nemocných s infarktem de facto není vůbec léčeno.
Národní strategie léčby infarktu primární PCI (CZ, NL) sníží tento
počet na pouhých 7%.
7
46
0
5
10
15
20
25
30
35
40
45
50
No reperfusion used
NL + CZ
Countries with
thrombolysis
dominance
% from all STEMI

31. And what about
Non-STEMI ?

33. Špaček R. et al.: VINO Study.
Eur Heart J. 2002 Feb;23(3):230-8.
30days 6months
Invasive
Conserv
7.5%
13.4%
1.6%
3.1%
p<0.05

36. •Unstable angina is disappearing in the current era of hs-Tn…..
•…..We can expect, that patients with coronary artery disease
will again (as many years ago) be classified as having either (a)
angina pectoris or (b) acute myocardial infarction.
•A requiem is a choral musical work that is performed at the
funeral of a great personage or at the close of an important
era. Has not the time arrived to prepare a requiem for
unstable angina ?
(Circulation. 2013;127:2452-2457.)

40. Hot topics in
acute PCI for AMI

41. Dr Adeel Shahzad
Dr Rod Stables (PI)
Liverpool Heart and Chest Hospital
Liverpool, UK
How Effective are
Antithrombotic Therapies in PPCI

42. Bivalirudin Heparin
GPI Bailout GPI Universal
ACUITY 9 % 97 %
ISAR REACT 4 0 % 100 %
HORIZONS 7 % 98 %
EUROMAX 9 % 70 %
↑ bleeding with ↑ GPI use

43. • Single centre RCT
• Trial recruitment: Feb 2012 - Nov 2013 22 months
• Bivalirudin v Unfractionated Heparin
• STEMI patients
• Randomised at presentation
• Acute phase management with Primary PCI
• Philosophy for clinical teams:
• Assess ‘Every Patient - Every Time’

44. • Dual oral anti-platelet therapy pre-procedure
• Heparin: 70 units/kg body weight pre-procedure
• Bivalirudin: Bolus 0.75 mg/kg
Infusion 1.75 mg/kg/hr - procedure duration
• GPI - Abciximab
• Selective (‘bailout’) use in both groups
• ESC guideline indications

45. Assigned to Heparin 914
Included in analysis 907
915 Assigned to Bivalirudin
905 Included in analysis
Consent not available
in surviving patients
Consent not available
in surviving patients
7 10
Received allocated Rx 900
Received no study drug 14
Treatment cross-over 0
LMWH pre-procedure 3
907 Received allocated Rx
7 Received no study drug
1 Treatment cross-over
4 LMWH pre-procedure

46. Characteristic Bivalirudin (%) Heparin (%)
P2Y12 use - Any 99.6 99.5
- Clopidogrel 11.8 10.0
- Prasugrel 27.3 27.6
- Ticagrelor 61.2 62.7
GPI use 13.5 15.5
Radial arterial access 80.3 82.0
PCI performed 83.0 81.6

47. Bivalirudin Heparin
n % % n
MACE 79 8.7 % v 5.7 % 52
Absolute risk increase = 3.0% (95% CI 0.6, 5.4)
Relative risk = 1.52 (95% CI 1.1 – 2.1) P=0.01

48. Event curve shows first event experienced

49. Bivalirudin Heparin
n % % n
Death 46 5.1 % v 4.3 % 39
CVA 15 1.6% v 1.2% 11
Reinfarction 24 2.7% v 0.9% 8
TLR 24 2.7% v 0.7% 6
Any MACE 79 8.7 % v 5.7 % 52

50. Bivalirudin Heparin
n % % n
Definite 23 3.3 % v 0.7 % 5
Probable 1 0.1 % v 0.1 % 1
Acute 20 2.9 % v 0.9 % 6
Subacute 4 0.6% v 0% 0
ARC definite or probable stent thrombosis events

51. Bivalirudin Heparin
n % % n
Major Bleed 32 3.5 % v 3.1 % 28
Relative risk = 1.15 (95% CI 0.7 - 1.9) P=0.59
Major Bleed BARC grade 3-5

52. • A unique study with 100% recruitment of eligible patients
Use of heparin rather than bivalirudin
• Reduced rate of major adverse events (NNT = 33)
• Fewer stent thromboses and reinfarction events
• Consistent effect across pre-specified subgroups
• No increase in bleeding complications
• Potential for substantial saving in drug costs

53. • 1. Bivalirudin is better drug and despite its price is cost-
effective.
• 2. Bivalirudin is better drug, but heparin is more cost-
effective.
• 3. Bivalirudin is just an expensive alternative to heparin
(both drugs are equally effective)
• 4. Heparin is better and bivalirudin should be abandoned.

55. After infarct artery PCI, patients were
randomized to (A) no further PCI procedures
or (B) immediate preventive PCI in noninfarct
arteries with more than 50% DS (preventive
PCI). Staged PCI in patients without angina
was discouraged.

56. What was known before PRAMI: evidence
and guidelines
Ph.Gabriel Steg
DHU-FIRE, Hôpital Bichat, Assistance Publique – Hôpitaux de Paris,
Université Paris – Diderot, INSERM U-698, Paris, France,
French Alliance for Cardiovascular clinical Trials
and Imperial College, Royal Brompton Hospital, London, UK

57. Worse Prognosis in Patients with MVD vs SVD After
Primary PCI
57
Parodi et al. Heart 2005;91:1541-44
Consecutive Patients Undergoing Primary PCI in a High Volume Center (N=1009)
n=511
n=498

58. After ACS, as many recurrent events are related to “non
culprit” and “culprit” lesions
Findings from the PROSPECT study:
MACE after Successful, Uncomplicated PCI in 697 Patients with ACS
Stone GW et al. N Engl J Med 2011;364:226-235

60. Complete vs Incomplete Revasc in DES Era: An
analysis from the NY State Database
Death Death/MI
Adjusted HR 1.23, P=0.01 Adjusted HR 1.27 P=0.002
Hannan et al. JACC Intv 2009;2:17-25

61. APEX-AMI: Multivessel PCI during initial
Procedure Associated with Increased Death
61Toma M, Buller CE et al. Eur Heart J 2010; 31:1701-7.

62. Non-IRA Revascularization routinely after Primary PCI –
a Meta Analysis
Bainey K, Mehta SR, Welsh R, AHJ 2013
Same-sitting:
favours culprit-only
Staged:
favours routine revasc

63. Steg PG, James SK et al. Eur Heart J 2012

64. ESC STEMI guidelines
3.5.4.9 Revascularization strategy for ST-segment elevation myocardial infarction
with multivessel disease
Apart from patients in cardiogenic shock, and in patients with continuous ischaemia after
opening the supposed culprit lesion, performing PCI of non-culprit vessels in the acute
setting is generally discouraged. The best strategy for STEMI patients with multivessel
disease, who underwent primary PCI of the infarct-related artery in the acute phase with
remaining multivessel disease, is still not well established.
Among the possible strategies, two that are frequently used are either a conservative
approach—which uses medical therapy after primary PCI, and revascularization of other
arteries only if there are symptoms or evidence of ischaemia in provocative tests—or a
staged revascularization approach, using PCI or coronary bypass surgery of non-infarct
arteries several days or weeks after primary PCI, often after confirmation of the stenosis
severity with measurements of fractional flow reserve. A multidisciplinary approach is often
needed, including a heart team and appropriate informed consent of the patient.
In STEMI patients with multivessel disease initially treated with primary or post-thrombolysis
culprit-artery PCI and confirmed presence of ischaemia in non-infarcted territories, staged
revascularization may be performed before discharge or in the days to weeks after initial
PCI
Steg PG, James SK et al. Eur Heart J 2012

65. ESC STEMI guidelines
Summary of indications for imaging and stress testing
Steg PG, James SK et al. Eur Heart J 2012

66. Bioresorbable vascular scaffolds
in acute STEMI
(PRAGUE-19 study)
Petr Widimský, Viktor Kočka, Martin Malý*,
Libor Lisa, Tomáš Buděšínský, Petr Toušek
University Hospital Kralovske Vinohrady
and *Central Military Hospital
Prague, Czech Republic

67. Inclusion criteria Exclusion criteria - clinical Exclusion criteria - angiographic
STEMI <24 hours from
symptom onset
Killip III-IV class (i.e. high likelihood of
death within BVS absorbtion time)
Infarct artery reference diameter
<2,3 mm or >3,7 mm (i.e. not suitable
for currently available BVS sizes)
Signed written
informed consent
Any other disease with probable
prognosis <3 years
Lesion lenth >24 mm (i.e. precluding
single BVS implantation)
Indication for oral anticoagulation (e.g.
atrial fibrillation)
Extensive infarct artery calcifications
or severe tortuosity
Contraindication to prolonged DAPT or
high likelihood of non-compliance to
DAPT
STEMI caused by in-stent restenosis
or stent thrombosis
No stent: not needed (POBA, thrombus
aspiration etc.) or not possible (failed PCI
or failed stent delivery)
79/311 (25.4%) pts fullfilled the prespecified
inclusion / exclusion criteria for BVS implantation

68. BVS vs. other stent: cardiac death / myocardial
infarction / TVR.
Number of patients available for follow-up in BVS/Control group is 40/57 at discharge, 36/48 at 1 month and 17/25 at 6 months.

69. Procedural result and BVS feasibility
• 85 BVS successfully implanted to 76/79 patients
• In 3 pts. BVS could not be delivered to LCX (BMS
2x succeeded, 1x failed)
• 72/76 BVS patients had ideal result (TIMI-3 flow,
no residual stenosis, no angiographically visible
dissection)
• 4/76 patients had TIMI-2 flow

70. Why BVS was not implanted to 75%
STEMI patients (n = 235)
12%
37%
17%
13%
9%
1%
5%
2% 4%
Reasons for exclusion PCI without stent
Too large artery (≥3,7 mm)
Killip III-IV
Artery calcifications or tortuosity
BVS size not on stock
Stent thrombosis as culprit lesion
Expected non-compliance to DAPT
Other illness with short prognosis
Oral anticoagulation
37% more STEMI pts. might receive BVS if size 4,0 mm would be available

71. BVS group – overall outcomes (n=76)
follow-up: 21 pts. >1 year, 52 pts. >6 months, 70 pts. >1 month
• Overall mortality: 1/76 = 1.3% (1 patient with anterior STEMI treated 18
hours after symptom onset died due to septal rupture occurring 4 hours
after P-PCI)
• Reinfarction (up to 16 months post PCI): 1/76 = 1.3% (1 BVS thrombosis
3 days after stopping ticagrelor, 10 days after hospital discharge)
• Stent thrombosis: 1/76 = 1.3%
• Stroke (up to 16 months post PCI): 3/76 = 3.9% (1 ICB after elective
neurointervention 95 days post PCI, 1 TIA during elective re-CAG 47
days post PCI, 1 spontaneous TIA 10 days after p-PCI)
• Clinical restenosis (up to 10 months post PCI): 0 = 0%

73. Endothelization at 1 month

74. Endothelization at 6 months

77. Conclusions
• BVS implantation in acute STEMI is feasible and safe.
• With the currently available size spectrum and expiration
times BVS can be used in 25-35% of STEMI patients.
Availability of 4,0 mm size would substantially increase this
proportion.
• OCT can be used safely to control BVS implantation in STEMI.
• The study will elucidate the role of CT angiography for long-
term BVS patency assessment
• Long-term follow-up will elucidate the future role of BVS in
STEMI.

79. Three young females (37-46 years)
with acute stroke (NIHSS 12-17)
and full neurologic recovery within 48 hours

82. 45-years mother from 3 children
11:30 sudden loss of consciousness, hemiplegia
12:30 CT scan
13:00 transfemoral angiography
13:30 thrombectomy (Solitaire)
13:45 conscious, speaking
16:00 moving (photo)
Next morning willing to go home (mRS 0)

83. Functional outcomes
Favourable outcome (mRs ≤2) in 48%. Mean mRs among survivors
treated within <120 minutes was 1.17 !

84. Our results are similar / better when compared to
endovascular treatment arms in the 3 largest
randomized trials (NEJM March 2013)
21,7 19,1 18,8
14,4
52
59
81
58
0
10
20
30
40
50
60
70
80
90
PRAGUE-16 IMS-III trial MR Rescue
trial
SYNTHESIS
trial
Mortality
Death/ severe invalidity
MeanmRS at 90 days
*SYNTHESIS included pts. with small strokes (NIHSS ≥2)
* * MR-Rescue included pts. with NIHSS ≥6
* *
*

85. PRAGUE trials overview
• PRAGUE-1: p-PCI vs. TL vs. facil.
PCI in STEMI (transport)
• P-2: p-PCI vs. TL in STEMI
(transport)
• P-3: p-PCI for late-presenting
STEMI
• P-4: off-pump vs. on-pump CABG
for all-comers
• P-5: 24-hour discharge after
STEMI
• P-6: off-pump vs. on-pump CABG
for high risk pts.
• P-7: abciximab in cardiogenic
shock
• P-8: clopidogrel pretreatment
before PCI
• P-9: ischemic mitral regurgitation
• P-10: trimetazidine in heart failure
• P-11: platelet activity in CABG
• P-12: surgical MAZE
• P-13: multivessel PCI in STEMI
• P-14: perioperative bleeding and
ischemia in non-cardiac surgery
• P-15: renal denervation
• P-16: acute stroke intervention
• P-17: anticoagulant + antiplatelet
therapy after PCI in pts with atrial
fibrillation
• P-18: ticagrelor vs. prasugrel in
STEMI
• P-19: bioresorbable vascular
scaffolds in STEMI
Published
Unpublished (failed)
Ongoing

86. Hot Line / Late Breaking Clinical Trials
presentations from the PRAGUE Study Group
• 1999 ESC: PRAGUE-1
• 2000 ESC: VINO
• 2002 ESC: PRAGUE-2 (30-day outcomes)
• 2002 ESC: PRAGUE-4 (early surgical outcomes)
• 2002 TCT: PRAGUE-2
• 2004 ACC: PRAGUE-4 (1-year CAG outcomes)
• 2006 WCC: PRAGUE-2 (5-yers f-u)
• 2007 ESC: PRAGUE-8
• 2009 ESC: PRAGUE-7
• 2012 ESC: PRAGUE-12
• 2013 ACC: PRAGUE-6
• 2013 EuroPCR: PRAGUE-19
• 2013 ESC: PRAGUE-14
• 2014 EuroPCR: PRAGUE-16

87. Ke stažení v PDF verzi:
www.kardio-cz.cz

88. The goal of modern cardiology:
To keep the routes open !