20 años de Angioplastia Primaria para el tratamiento del Infarto. Experiencia y evolución de las...

20 years of Primary PCI for STEMI:Czech experience and evolution of networks.

Petr WidimskyCharles University Prague &

University Hospital Kralovske Vinohrady, PragueCzech Republic

How to reperfuse the obstructed route ?Before 1985: no routine treatment available1986-1993: dissolving the clot (thrombolysis) in 25% of all STEMIs1993-2002: reperfusion & revascularization (p-PCI) for 50% of STEMIs (locals only)After 2002: reperfusion & revascularization (p-PCI) for all STEMIs (transport)

Geoff Hartzler (USA) 19821st primary PCI

Felix Zijlstra & Zwolle Group (NL) 1988-931st randomized trial on primary PCI

Otto Klein (CZ) 19291st diagnostic

cardiac catheterization Andreas Gruntzig (CH) 19771st PTCA

„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

1990 cup of coffee in Rotterdam1993-4 PCI training in Zwolle1995 end of thrombolysis in Prague1997-9 the PRAGUE-1 study2002 Czech STEMI guidelines2008 Stent for Life

Thrombolysis(50% success rates7% reocclusion risk)

Primary PCI (90% success rates3% reocclusion risk)

Modern therapy of AMI:

Thrombus removal,

Flow restoration

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

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

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%

PRAGUE-2: 30-days outcomesEur 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

Metaanalysis of 23 studies TL vs. PCI(Keeley et al., Lancet 2003; 361: 13-20)

9

7 7

32

1

14

8

0

2

4

6

8

10

12

14

Mortality Re-MI Stroke Comb.end-

point

TL

PCI

% n=7739

Czech Republic:Experience with primary PCI

and STEMI networks

Čas lék čes 1983; 122: 694-6.

Dec. 20, 1982

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 onduty

Cardiologist day-hours

Cardiologist 24/7, butno PCI

Cardiologist + PCI24/7

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

5-leté přežívání po PCI

5-leté přežívání po trombolýze

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)

….. 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

Evolution of PCI rates in the Czech R.

3201829

9270

16338

2167622545

21624

0

5000

10000

15000

20000

25000

1990 1995 2000 2002 2004 2009 2013

PCI/rok/ČR

PCI/rok/ČR

PRAGUE-11999

PRAGUE-22002

P-PCI networks Czech Rep.

During 1999 – 2005 period the implementation of the „PRAGUE“ trials resultscompletely 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

Stent for Life

≥600 p-PCI / million / year400-599 p-PCI / million / year200-399 p-PCI / million / year<200 p-PCI / million / yearData not known

Annual Incidence of Primary PCIs

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 withthrombolysisdominance

% from all STEMI

And what aboutNon-STEMI ?

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

•Unstable angina is disappearing in the current era of hs-Tn…..•…..We can expect, that patients with coronary artery diseasewill 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 importantera. Has not the time arrived to prepare a requiem forunstable angina ?

(Circulation. 2013;127:2452-2457.)

Hot topics inacute PCI for AMI

Dr Adeel Shahzad

Dr Rod Stables (PI)

Liverpool Heart and Chest Hospital

Liverpool, UK

How Effective are

Antithrombotic Therapies in PPCI

Bivalirudin Heparin

GPI Bailout GPI Universal

ACUITY 9 % 97 %

ISAR REACT 4 0 % 100 %

HORIZONS 7 % 98 %

EUROMAX 9 % 70 %

↑ bleeding with ↑ GPI use

• 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’

• 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

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

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

Bivalirudin Heparinn % % 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

Event curve shows first event experienced

Bivalirudin Heparinn % % 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

Bivalirudin Heparinn % % 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

Bivalirudin Heparinn % % 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

• 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

• 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.

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.

What was known before PRAMI: evidenceand guidelines

Ph.Gabriel StegDHU-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

Worse Prognosis in Patients with MVD vs SVD After

Primary PCI

57Parodi et al. Heart 2005;91:1541-44

Consecutive Patients Undergoing Primary PCI in a High Volume Center (N=1009)

n=511

n=498

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

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

APEX-AMI: Multivessel PCI during initial

Procedure Associated with Increased Death

61Toma M, Buller CE et al. Eur Heart J 2010; 31:1701-7.

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

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

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

ESC STEMI guidelinesSummary of indications for imaging and stress testing

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

Bioresorbable vascular scaffoldsin acute STEMI

(PRAGUE-19 study)

Petr Widimský, Viktor Kočka, Martin Malý*,

Libor Lisa, Tomáš Buděšínský, Petr ToušekUniversity Hospital Kralovske Vinohrady

and *Central Military Hospital

Prague, Czech Republic

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

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.

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 visibledissection)

• 4/76 patients had TIMI-2 flow

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

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 hoursafter P-PCI)

• Reinfarction (up to 16 months post PCI): 1/76 = 1.3% (1 BVS thrombosis3 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 electiveneurointervention 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%

Endothelization at 1 month

Endothelization at 6 months

Conclusions

• BVS implantation in acute STEMI is feasible and safe.

• With the currently available size spectrum and expirationtimes BVS can be used in 25-35% of STEMI patients. Availability of 4,0 mm size would substantially increase thisproportion.

• 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.

Three young females (37-46 years)

with acute stroke (NIHSS 12-17)

and full neurologic recovery within 48 hours

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)

Functional outcomes

Favourable outcome (mRs ≤2) in 48%. Mean mRs among survivors

treated within <120 minutes was 1.17 !

Our results are similar / better when compared to

endovascular treatment arms in the 3 largest

randomized trials (NEJM March 2013)

21,7 19,1 18,814,4

5259

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

Mean mRS at 90 days

*SYNTHESIS included pts. with small strokes (NIHSS ≥2)

* * MR-Rescue included pts. with NIHSS ≥6

* **

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

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

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

The goal of modern cardiology:

To keep the routes open !