Treatment of STEMI in 2011: Management of Patients Presenting to Non-PCI Centers NonStephen G. Ellis, M.D.

Professor of Medicine Director Invasive Services Co-Director Cardiac Gene Bank

2009 ACC Guidelines: Triage and Transfer for PCI

FJ Kushner et al., 2009 STEMI Guideline Updates

SGE; 0410-1, 48

2009 ACC Guidelines: Triage and Transfer for PCI

How do you tell?

FJ Kushner et al., 2009 STEMI Guideline Updates

SGE; 0410-1, 48

2009 ACC Guidelines: Triage and Transfer for PCI

Which one?

FJ Kushner et al., 2009 STEMI Guideline Updates

SGE; 0410-1, 48

2009 ACC Guidelines: Triage and Transfer for PCI

How high risk?

FJ Kushner et al., 2009 STEMI Guideline Updates

SGE; 0410-1, 48

2009 ACC Guidelines: Triage and Transfer for PCI

Who should get lytics?

FJ Kushner et al., 2009 STEMI Guideline Updates

SGE; 0410-1, 48

2009 ACC Guidelines: Triage and Transfer for PCI

-Less emphasis on difference between DTN and DTB per se -A b l Ambulance lytics for presentation < 90 min l ti f t ti i -Otherwise PCI except for high risk, early presenting pts with long DTB delay and low risk of bleeding -Keep decision tree simple (thinking->delays) p p (thinking( g y )

FJ Kushner et al., 2009 STEMI Guideline Updates

SGE; 0410-1, 48

2009 ACC Guidelines: Triage and Transfer for PCI

Which one?

FJ Kushner et al., 2009 STEMI Guideline Updates

SGE; 0410-1, 48

PCI After Lytics/GPI y

Facilitated PCI/Rationale
Early reperfusion salvages myocardium In many areas, door to balloon times exceed ACC recommended <90 min d d 90 i Some combination of antiplatelet + lytic treatment can open IRA before PCI in many cases

SGE / jd 02_06

ASSENT IV - Trial Design g

ASSENT IV Study Design
STEMI patients < 6 hrs, PCI within 1-3 hrs N=4000 Randomization 1:1, Open Label UFH (60IU/kg) and Aspirin UFH (70IU/kg) and Aspirin

Clopidogrel only after angiogram when decision for stent implantation is made Primary PCI IIb/IIIa investigator discretion (clopidogrel if stent)

Pre-treatment with Full Dose TNK followed by Primary PCI IIb/IIIa bail out only* (clopidogrel if stent)

Primary Endpoint * : Composite of Death or Cardiogenic Shock or Congestive Heart Failure within 90 Days
* Used in only 9.6%

Stopped on Basis of Mortality at 30 Days pp y y

ASSENT IV Preliminary Data
Mortality (%)
10 8 6 4 2 0 50/828 32/835 6 3.8

TNK + PCI PCI alone P = 0.04

6.7 vs 5.0% (p=.14) at 90 days 18.8 vs 13.7% (p=.006) MACE at 90 days

Van de Werf ESC 2005

Acute MI
Platelet Activation by Fibrinolytics
Normalized Maximal Aggregation Rate
1.5

t-PA SK

1.0

0.5 0 50 100 150 200 250

Time (min)
Rabbit model, .05mM ADP as agonist
Rudd and Loscalzo, CircRes 90 SGE; 0802-3, 22

FINESSE: Study Design y g

Acute ST Elevation MI (or New LBBB*) within 6h pain onset Presenting at Hub or Spoke with estimated time to PCI between 1 and 4 hours

*Localized IMI excluded

Placebo Placebo

Randomize 1:1:1 N=3000

*Only 5U if 75 Reteplase (5U+5U)* Abciximab

Placebo Abciximab

Transfer To Cath Lab ASA, unfractionated heparin 40U/kg (max 3000u) or enoxaparin (0.5 mg/kg IV + 0.3 mg/kg SC) substudy only (0 5 03

Abciximab

Placebo
Primary PCI with Abciximab Infusion (12 h)

Placebo

Primary endpoint at 90 days: All-cause mortality, resuscitated VF occurring > 48H, cardiogenic shock, or readmission/ED visit for CHF

All Cause Mortality Through 1 Year y g

7.4% 7.0% 7 0% 6.3%

FINESSE: 1 Year Mortality by Infarct Location

All Cause Mortality Through 1 Year 25% 20% Per rcentage 15% 10% 5% 0% Nonanterior (n=1279) Anterior (n=1173) 4.6% 4.9% 6.1%

p=.093
9.9% 10.0% 6.5%

Primary PCI with In Lab Abciximab Abciximab Facililated PCI Abciximab/Reteplase Facilitated PCI

HORIZONS: Three-Year All-Cause Mortality ThreeAll10

Bivalirudin alone (n=1800) Heparin + GPIIb/IIIa (n=1802)

A AllAll-Caus Morta se ality (%) )

9 8 7 6 5 4 3 2 1 0 0 3 6

7.7%
4.8%

5.9% 5 9%
3-yr HR [95%CI]= 0.75 [0.58, 0.97] P=0.03

3.4%
1-yr HR [95%CI]= 0.71 [0.51, 0.98] 0 71 [0 51 0 98] P=0.04
9 12 15 18 21 24 27

30

33

36

Number at risk Bivalirudin alone Heparin+GPIIb/IIIa

Months
1800 1802 1689 1670 1660 1643 1633 1593 1611 1568 1574 1525 1098 1043

Impact of Pre-randomization Heparin in Prethe HORIZONS-AMI Trial HORIZONS30 Day MACE 10 8 6 4.6 4 2 0 5.6 7.2 5.2 52
30 Day Major Bleeding 10

Bivalirudin Heparin + GP IIb/IIa 7.5

8.5 8 6 4.8 4 2 0 5.2 52

No Pre-treatment Pre-treatment (N 2553) (N=2553) (N 1042) (N=1042)

No Pre-treatment Pre-treatment (N 2553) (N=2553) (N 1042) (N=1042)

SGE; 0310-3, 71

Astroulakis Z, Hill JM, Eur Heart J Suppl 2009;11:C13-C18 2009;11:C13-

Impact of Pre-randomization Heparin in Prethe HORIZONS-AMI Trial HORIZONS30 Day MACE 10 8 6 4.6 4 2 0 5.6 7.2 5.2 52 30 Day Major Bleeding 10 8.5 8 6 4.8 4 2 0 5.2 52 Bivalirudin Heparin + GP IIb/IIa 7.5

No Pre-treatment Pre-treatment (N 2553) (N=2553) (N 1042) (N=1042)

No Pre-treatment Pre-treatment (N 2553) (N=2553) (N 1042) (N=1042)

SGE; 0310-3, 71

Astroulakis Z, Hill JM, Eur Heart J Suppl 2009;11:C13-C18 2009;11:C13-

STEMI
Importance of Early Heparin Administrative/Horizons
Pre Randomization Heparin 3.0 2.5 Acute Stent % 1.5 Thrombosis 1.0 10 0.5 0.0 0.1 01 Bivalirudin Randomized Heparin + G I epa GP
SGE; 0310-3, 72

P = 0.006

2.6 26

Yes Y No

2.0
P = 0.02

0.9 09

0.8

Dangas, ACC 2009

Triton TIMI 38 STEMI

UA/NSTEMI patients ti t N=10,074 All ACS/PCI patients N=13,608
2 patients were missing data for primary or secondary

STEMI patients N=3,534 N 3 534 Within 14 days for ongoing or recurrent ischemia

STEMI <12 hrs

Primary PCI N=2,438 (69%)

Secondary PCI N=1,094 (31%)*

Clopidogrel N=1,235

Prasugrel N=1,203

Clopidogrel N=530

Prasugrel N=564
SGE; 0411-1, 8

Montalescot G et al. Lancet 2009;373:72331 2009;373:723

TRITON TIMI-38 TIMI15

STEMI Cohort N 3534 N=3534

Clopidogrel

CV Death / MI / Stroke

12.4% 10.0%

Percen (%) nt

10

9.5% 6.5% 6 5% Prasugrel

HR 0.68 (0.54-0.87) (0 54-0 87) P=0.002

HR 0.79 (0.65 0.97) (0.65-0.97) P=0.02 NNT = 42 Prasugrel Clopidogrel

2.4 2.1 21

TIMI Major NonCABG Bleeds

180 270 360 Days From Randomization Montalescot et al Lancet 2008.Adapted with permission
from Antman EM.

30 60 90

450
SGE; 0410-8, 31

Triton TIMI 38: Stent Thrombosis: Definite/Probable

Stent Thrombosis (%) 3.0

2.8% p=0.02 RRR=42% 1.6% HR=0.58 (0.360.93) NNT=83

2.4%
2.0

p=0.008 RRR=51% 1.2%

1.0

Clopidogrel Prasugrel 350 400 450

0.0

50

100

150

200 250 Time (Days)

300

Montalescot G et al. Lancet 2009;373:72331 2009;373:723 SGE; 0411-1, 10

2009 ACC Guidelines: Triage and Transfer for PCI

ASA, Prasugrel*, heparin, BB, statins *May give with PCI (clopidogrel needs loading) g)

FJ Kushner et al., 2009 STEMI Guideline Updates

SGE; 0410-1, 48

2009 ACC Guidelines: Triage and Transfer for PCI

How high risk?

FJ Kushner et al., 2009 STEMI Guideline Updates

SGE; 0410-1, 48

CARESS-INCARESS-IN-AMI: Design N g
Designed to address optimum treatment in pts for whom primary PCI not readily a a ab e available Comparison, after half dose reteplase+abciximab, between routine etep ase abc ab, bet ee out e immediate referral for cath/PCI and selective rescue PCI approach in pts who do not qualify for primary angioplasty High risk patients only (Killip class > 2, EF <35%, ST elevation cumulative > 15 mm)

Di Mario et al. Lancet 2008;371.559 SGE; 0410-8, 61

CARESS-INCARESS-IN-AMI: Primary Outcome

primary outcome (composite of all cause mortality, reinfarction, & refractory MI within 30 days) occurred significantly less often in the immediate PCI group vs. standard care/rescue PCI group

10.7%

4.4%
HR=0.40 (0.21-0.76)

Di Mario et al. Lancet 2008;371:559.

SGE; 0410-8, 64

Transfer AMI
Cath/PCI After Lysis: Routine or Rescue?
1,059 pts STEMI <12 hrs >48 and any of: SBP <100, 24 - <48 HR>100, Killip 2-3 or 212 - <24 RVMl rxd with Tenecteplase 11 - <12 10 - <11 R routine or 9 - <10 rescue b based angio/PCI d i /PCI 8 - <9 Concomitant rx: 7 - <8 ASA +/- Clopidogrel; +/6 - <7 5 - <6 UF or LMWH 4 - <5 1 endpoint: death, re-MI, re3 - <4 rec ischemia, CHF, 2 - <3 CGS @30 days 1 - <2
0 - <1

Time from Randomization to Cardiac Catherization, (hr)

1.0
0.8 0.6 06 0.4

Cumulative Incidence Primary End Point

0.20 0.15 0.10
0.05 0 05 0.00

Routine early PCI, Standard Treatment, (N=529) (N=463) Routine early PCI PCI, Standard Treatment, Treatment (N=463) (N=529)

10

15

20

25

30

Standard Treatment

0.2 p =0.004 0.0 0

Routine early PCI

No. of Patients

50

100 150 200

Days from Randomization

442 488 434 486 434 483 433 481 433 480

10

15

20

25

30

N at risk t i k Standard Early PCI

522 537

432 478

Cantor, NEJM 360:2705, 2009

SGE; 0609-6, 29

Intervention After Fibrinolysis y

Probability of death, non-fatal reinfarction, or ischemiadriven revascularization

GRACIA I 500 Patients 0.5 12 0 5-12 hrs of sx ST elevation in 2 leads Excluded: shock or pressor dependency Randomized to either routine cath PCI within 24 hrs or Ischemia only driven cath (20% crossover) 1 end pt: death, MI or ischemia reg revasc at 12 months Fernandez-Aviles Lancet 04

30
Conservative

20
intervention

10 0

2 230 225

4 228 217

6 226 211

8 223 208

10 222 202

12 221 195

Number at risk Intervention 248 Conservative 251

Time since randomization (months)

Probability of death, non-fatal reinfarction 30

20
Conservative

10
intervention

10

12

Number at risk Intervention 248 Conservative 251

Time since randomization (months)

236 235

235 230

232 226

229 225

228 221

227 217

SGE; 0411-11, 1

Clinical Outcome at 30 Days NORDISTEMI

25 20 15
(%) 21% RR 0.49 (0.27-0.89) (0.27P=0.03 RR 0.45 (0.18-1.16) (0.18P=0.14 9.8% 4.5% 2.3% 2.2%
conservative invasive

10 5 0

10%

Death, re-MI, restroke, new ischemia

Death, re-MI, restroke

Death

Bohmer E. JACC 55:102, 2010 n=266 patients > 90 min from FMC->PCI, rxd with FMCtenecteplase (not selected for high risk) Invasive- PCI (89%) 163 min, Cons (71%) Invasive3 days after TNK

SGE; 0410-1, 13

2009 ACC Guidelines: Triage and Transfer for PCI

All but very Low risk

FJ Kushner et al., 2009 STEMI Guideline Updates

SGE; 0410-1, 48

STEMI: Summary + Conclusions y

PCI trumps primary lytics except y y sx < 90 min if lytics given quickly (ambulance) very long transfer times (time depends on patient risk profile) ti t i k fil ) No role for routine facilitated PCI If lytics are given, moderate and high risk patients given should be transferred for cath/PCI immediately => pharmacopharmaco-invasive strategy with adequate antiantiplatelet therapy l t l t th DAP with prasugrel (except when contraindicated), early BB, ACE-I, statins are also important ACE-

SGE; 1109-9, 32

STEMI Triage for Non Cath Lab Hospitals

Final Word
Have protocol for patient transfer in good weather and bad (eg helicopter, ground transport) worked out with receiving hospital(s) Post t i P t triage protocol in the ED t l i th - should be relatively simple - should include drugs (minimize iv drips favor drug drips, that can be given iv push) Post contraindications to lytics also

SGE; 1109-9, 32