Primary PCI VS Thrombolysis in

STEMI, Positional Statement

Ahmed Magdy, MD,
FACC, FSCAI
National Heart
Institute

Change in Approach to AMI

19902002

20032011

AcuteMI

Lytic

AcuteMI

Facilitated
Lytic/LMWH

Transfer for Cath with Lytic failure

Transfer emergently all patients

2007 focused update of the ACC/AHA STEMI

guidelines

Reperfusion Therapy in STEMI

Importance of Rapid Time to

Treatment With Fibrinolysis in STEMI
4.0
Absolute % difference
in mortality at 35 days

3.5%

3.0

2.5%

2.0

1.8%

1.6%

1.0
0.5%
01
23
46
7 12
12 24
Time from onset of symptoms to treatment (hours)

0.0

The Fibrinolytics Therapy Trialists collaborative group. Lancet

Lancet.. 1994
1994;; 343:
343:311
311..

PCI In-hospital Mortality

vs Door to Balloon Time
12.2

14
12

N= 2,322
8

10
8

Inhosp
Death
Rate

6.1
4.9

6
4
2
N=384

N=493

0-1.4

1.5-1.9

N=750

N=673

2.0-2.9

>3.0

Brodie BR, JACC 47, 2006

Door to Balloon Time (hours)

III. Timely Reperfusion

1. Time is Myocardium
2. Infarct Size is Outcome
Mortality Reduction (%)

100

Symptom onset to hosp

D Arrival 2 hr

80

60

Shifts in
Shift
i outcome
t
with
ith
different ttt strategies
A to B no benefit
A to C Benefit
B to C Benefit
D to B Harm
D to C Harm

Thrombolysis given, 2 hr

C
40

lysis induced reperfusion 3 hr

onset to balloon 3 hr

20

Extent of
0 Myocardial Salvage
0

12

16

20

24

Time From Symptom Onset to Reperfusion Therapy, h

Time-independent Period
Critical Time
Time--dependent Period TimeGoal: Open InfarctInfarct-Related Artery
Goal: Myocardial Salvage

Gersh BJ, et al. JAMA

JAMA.. 2005
2005;;293:
293:979
979..

PCI is better than LYSIS!

Primary PCI vs Lysis for STEMI
Meta-analysis of 23 trials
Short Term Events

16
14
12
10
8
6
4
2
0

P<0.0001
14

P=0.0003
P<0.0001

p=0.0004

5
3

P<0.0001
1 2
0.05

Death

Re MI

PTCA
Thrombolytic

Total
CVA

ICH

Death +
Re-MI +
CVA

Keeley, Lancet Jan 2003

Recent Influences of Practice

Salvage is Time Dependant

if DoorDoor
to-Balloon completed
in a timely fashion

Superiority of PPCI over fibrinolysis

Acknowledgement
g
that Time Matters in PPCI
Recommendations for time to reperfusion updated

15
5

10

Circle sizes = sample size of the

individual study.

0
-5

Absolu
ute Risk Differencce in
Death (%)

Mortality rates with primary PCI as a

function of PCI-related time delay

20

40

Solid line= weighted metaregression.

P=
Benefit
0.006
Favors
62 min
PCI
H
Harm
Favors
Lysis
60
80
100

PCI-Related Time Delay (door-to-balloon - door to needle)

For Every 10 min delay to PCI: 1% reduction in mortality difference towards
lytics

Nallamothu BK, Bates ER. Am J Cardiol. 2003;92:824-6

*PPCI Better > Pre-Hospital Lysis >

In-Hospital Lysis

*Transfer for PCI is better than

LYSIS!

(In a timely manner)

Assessing Reperfusion Options for Patients

with STEMI1
STEP 1: Assess time from symptom onset, risk of STEMI, risk of
thrombolysis, time for transport to PCI lab
STEP 2: Determine whether fibrinolysis or invasive strategy is
preferred*
Fibrinolysis preferred if:

Invasive strategy preferred if:

Early presentation (<3 hours)

Skilled PCI lab with surgical backup
available
Invasive strategy not an option
Delay to invasive strategy, (heavy High risk (i.e. cardiogenic shock)
traffics)
Contraindications to fibrinolysis
Late presentation (>3 hours)
Diagnosis of STEMI is in doubt

*If presentation is <3 hours from onset and no delay to

an invasive strategy, there is no preference

for either strategy
JACC 44: 671, 2004

PCI post thrombolysis in STEMI:

Prehospital TL
+ immediate transfer

CAPTIM

Delayed PCI
b f
before
di
discharge
h

Open artery hypothesis

OAT SWISSI II

Rescue PCI
for failed TL

<24h post lysis

ESC PCI GL 05

SIAM III
GRACIA 1
CAPITAL AMI
WEST
Immediate postpost-lysis
CARESS
TRASFERMI
facilitated PCI
PACT PRAGUE GRACIA 2 ASSENT-4 FINESSE

RESCUE, REACT

PCI post thrombolysis in STEMI:

Following successful thrombolytic therapy
therapy,
patients should undergo early angiography
and PCI of their IRA

Defined: more than 50

50%
% reduction in ST
elevation in 60 to 90 min post TL Rx

Defined: less than 24hours

24hours post TL Rx

PCI post thrombolysis in STEMI:

RATIONALE
1 Risk
1.
Ri k off reocclusion high
hi h
2. Early angiographic risk stratification
3. High likelihood of residual complex
stenosis despite successful TL Rx

Rescue PCI is better than Lysis!!

REACT: 6 month Primary composite
(Death, MI, CVA, or severe heart failure)

35

31.0

p<0.001

p=0.002

29.8

30
25

20
15.3

15
10
5

The primary composite

endpoint of death, MI, CVA or
severe heart failure at 6 months
was significantly lower in the
rescue PCI group compared
with either the repeat
thrombolysis group or the
conservative management
group

0
Repeat
Thrombolysis

Rescue PCI Conservative

Management
Presented at AHA 200

PCI
i better
is
b tt than
th
Facilitated PCI
????

10

11

Primary, secondary and bleeding end

points in FINESSE
End points

Primary
PCI (%)

Abciximab
+PCI%)

(abcixima/
reteplase)
-facilitated PCI
(%)

p,
combined+
PCI vs
primary PCI

p, combin
+PCIvs
abciximab-abciximab
facilitate

Primary end
point*

10.7

10.5

9.8

NS

NS

All--cause
All
mortality

4.5

5.5

5.2

NS

NS

Complications
of MI

8.9

7.5

7.4

NS

NS

Death

4.5

5.5

5.2

NS

NS

TIMI major
bleeding

2.6

4.1

4.8

0.025

NS

TIMI minor
bleeding

4.3

6.0

9.7

<0.001

0.006

FINESSE

Best trial available

Slow enrollment, therefore underpowered
40% spoke hospitals with D-B 155 min
Increase bleeding (are all regimens =?)
Signals in Ant MI
MI, High Risk,
Risk < 3 hrs

12

Immediate PCI
is better than
LYSIS +/- Delayed PCI!

13

SIAM 3
Event Free Survival
(Death, Re
Re--infarction, Intervention, Ischemia)

14

Pharmacoinvasive
(Facilitated) PCI
is better than Lytic +
Rescue PCI

15

16

Comments on CARESS
Again use of potent antiplatelet agent
(abciximab), platelets inactivated at time of
PCI, (In ASSENT IV < 10% use!!)
Bleeding reassuring as pts > 75yo excluded
Median time from TL Rx to PCI 212 min

Post-Lysis PCI studies

60
50

SIAM III

PCI
"Conservative"

25.6

N=1436
N=
1436
21

20
9

10
P=0.001

CAPITAL MI CARESS

50 6
50.6

40
30

GRACIA--1
GRACIA

refract
Is/D/MI/TLR

P=0.0008

24.4

11.6
P=0.04

11.1
4.1 P=0.001

D/MI/Revasc D/MI/UA/stoke refract Is/D/MI

17

High Risk ST Elevation MI within 12 hours of symptom onset

TNK + ASA + Heparin / Enoxaparin + Clopidogrel

Community
Hospital
Pharmacoinvasive
Strategy
gy
Emergency Urgent Transfer
to PCI Centre
Department

Standard Treatment
Assess chest pain, ST resolution
at 6060-90 minutes after randomization
Failed Reperfusion*

PCI Centre
Cath Lab

Cath / PCI within 6 hrs

regardless of
reperfusion status

Cath and Rescue

PCI GP IIb/IIIa
Inhibitor

Successful Reperfusion
Elective Cath
PCI
> 24 hrs later

Repatriation of stable patients within 24 hrs of PCI

* ST segment resolution < 50% & persistent chest pain, or hemodynamic instability
Randomization stratified by age (75
(75 vs. > 75)
75) and by enrolling site

18
16
14
12
10
8
6
4
2
0
0

Primary Endpoint: 3030-Day Death, re

re--MI,
CHF, Severe Recurrent Ischemia,
% of Patients
Shock
16..6
16

n=496
n=508

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

10..6
10

Standard PCI > 24 hrs (n=496)

Invasive < 6 hrs (n=508)
5
422
468

10
15
20
Days from Randomization
415
415
414
466
463
461

25

30

414
460

412
457

18

Summary
Pharmacoinvasive Strategy of routine early
PCI within 6 hrs after thrombolysis is
associated with a 6% absolute ((46% relative))
reduction in the composite of death, re-MI,
recurrent ischemia, HF and shock
is not associated with any increase in
transfusions, severe bleeding despite high
use off GP IIb/IIIa
IIb/III in
i PCI

Benefit seen despite high cath/PCI rates in

Standard Treatment group (including ~40% rescue
PCI)

19

Thrombolysis catching up with PCI in

STEMI, especially in lower-risk patients
Observational prospective database (July 2007
to December 2009) of patients with STEMI
admitted to 73 Belgian hospitals: 25 hospitals
had PCI facilities and 48 hospitals did not.
Outcome was in-hospital mortality, and patients
were stratified into low,
low intermediate,
intermediate and
high risk according to TIMI score.
Arch Intern Med 2011; 171: 544-9

20

Thrombolysis catching up with PCI in

STEMI, especially in lower-risk
patients
There were 5,295
5 295 eligible patients in the
registry, 4,574 (86.4%) were treated with
primary PCI and 721 (13.6%) received
thrombolysis. Of those receiving thrombolysis,
603 (83.6%) underwent subsequent invasive
evaluation.
l i
TIMI risk
i k scores were low
l
in
i
1,934, intermediate in 2,382, and high in 979.

Arch Intern Med 2011; 171: 544-9

Thrombolysis catching up with PCI in

STEMI, especially in lower-risk patients
In
In-hospital
hospital mortality was similar in the two
groups, 5.9% (PCI) vs. 6.6%, and after
adjustment for baseline risk profile the
difference was significant only in the highrisk group

21

The authors conclude that in

current practice
thrombolysis
y is normally
y followed byy invasive
intervention, immediate PCI only has an
advantage for in-hospital mortality in patients at
high risk.
Early thrombolysis followed by later invasive
evaluation
l ti seems tto b
be superior
i tto delayed
d l
d PCI
when door to balloon time is over 60 minutes.

In summary: European GL

22

(From 2007 STEMI Update, Section 5)

1. Facilitated PCI using regimens other than full-dose
fibrinolytic
fib
i l ti therapy
th
might
i ht b
be considered
id d as a
reperfusion strategy when all of the following are
present:
a. Patients are at high risk,
b. PCI is not immediately
y available within 90
minutes,
c. Bleeding risk is low (younger age, absence of
poorly controlled hypertension, normal body weight).
(Level of Evidence: C)

2009 Joint STEMI/PCI Focused Update

Class IIa

1. It is reasonable for high-risk* patients who receive

fibrinolytic therapy as primary reperfusion therapy at a
non PCI capable facility to be transferred as
nonPCI-capable

ASAP to a PCI-capable facility where PCI

can be performed either when needed or as
a pharmaco-invasive strategy.
Consideration should be given to initiating a
preparatory antithrombotic (anticoagulant plus
antiplatelet) regimen before and during patient transfer
to the catheterization laboratory (14,15).
(Level of Evidence: B)

23

Latest European and US STEMI

Guidelines Compared and Contrasted
Both Discourage Facilitated Reperfusion
Both Endorse Newer Anticoagulants
both note it would be "reasonable"
"
bl " to
t perform
f

early angiography for risk stratification in

patients not undergoing primary PCI, but the
ESC goes a step further by supporting routine
angiography (with PCI if indicated) 3 to 24 hours
after successful fibrinolysis based on several recent
studies, including the GRACIA trials.

What conclusions can we make!

PCI centers should do PCI (in a timely manner <90
min)
Short Distance Transfer Pts should have PCI (in a
timely manner <120?)
Pharmcoinvasive PCI is an excellent choice for Pts
with expected delay!!
The ideal regimen and timing of PCI remain
unclear!

24

25