Facilitated PCI: Use of Lytics in the ED Delayed PCI “The Rock Rokos” Lytics “Italian Stallion...

Facilitated PCI: Use of Lyticsin the ED

Delayed PCI“The Rock Rokos”

Lytics“Italian Stallion Hollander”

Ivan C. “The Rock” Rokos, MD

Facilitated PCI:Use of Lytics in the ED?

Ivan C. Rokos, MD, FACEP

Emergency Physician

Asst. Clinical Professor, UCLA

Staff Physician, Olive View-UCLA

Staff Physician, Northridge Hospital

[email protected]

Disclosures

• Research & Consulting “Modest”– Medicines Co– Millenium (Schering-Plough)– Genentech– Sanofi-Aventis

“Shock & Awe”

On-site primary PCI (PPCI) is superior toon-site fibrinolytics!!

2004 STEMI Guidelines

• Page 681… “For facilities that can offer PCI, the literature suggests that this approach is superior to pharmacological reperfusion”

STEMI, ST-elevation myocardial infarction. J Am Coll Cardiol. 2004;44:671–719.

2004 STEMI Guidelines

• Page 682… “Given the current literature, it is not possible to say definitively that a particular reperfusion approach is superior for all patients, in all clinical settings, [and] at all times of the day.”

J Am Coll Cardiol. 2004;44:671–719.

Transfer PCI vs FibrinolyticsWhere do you draw the line on

time to reperfusion?

Door-to-Balloon (D2B) Zones for PPCI in STEMI

• <90 Minutes GREEN zone

• 90–120 Minutes YELLOW zone

• >120 Minutes RED zone

GREEN zone

National Registry of Myocardial Infarction D2B (minutes) versus

Mortality

0

1

2

3

4

5

6

7

8

<90 91-120

121-150

>1500

0.2

0.40.60.8

11.2

1.41.61.8

<60 61-90

91-120

121-150

151-180

Odds of in-hospital mortalityIn-hospital mortality regardless of

symptom onset or risk

P < 0.001P < 0.001

Cannon CP, et al. JAMA. 2000;283:2941–2947.McNamara RL, et al. J Am Coll Cardiol.

2006;47:2180–2186.

D2B Alliance GOAL: ≥75% rate of D2B ≤90 Min

1. Emergency physician activates the cath lab2. One call activates the cath lab3. Cath lab team ready in 20–30 minutes4. Prompt data feedback5. Senior management commitment6. Team-based approach

Optional = Prehospital electrocardiogram to activatethe cath lab

D2B Zones for PPCI in STEMI



• >120 Minutes RED zone RED zone

PPCI >120 Minutes Is NOT an Acceptable Benchmark

• ACC/AHA STEMI Guidelines– 120 minutes or less (1999, p 904)– 90 minutes or less (2004, p 684)

• Joint Commission Core Measures– 120 minutes or less (Initially)– 90 minutes or less (July 1, 2006)

D2B Zones for PPCI in STEMI



• >120 Minutes RED zone YELLOW zone

ACEP 2006 Clinical PolicyRecommendations

• What are the indications for fibrinolytics in patients being treated at or transferred to aPCI center?

• Level A = None

• Level B = Lytics for STEMI <3 hours after symptom onset and expected D2B exceeding90 minutes

• Level C = Lytics for high-risk STEMI <6 hours after symptom onset and expected D2B>90 minutes (?define high risk?)

Debate With Dr. Hollander(an Academic Komodo Dragon)

• Voracious academic

• Data-slicing teeth

• Whip-like wit

• Fast on his feet

• The lizard (or Dr H.)will often kill and dismember its preyon the spot

(National Wildlife Federation)

My Proposed D2B Goals in 2007

• On-site PPCI D2B ≤90 minutes

• Urban transfer PCI (Trf-PCI) D2B ≤90 minutes

• ?Rural Trf-PCI D2B ≤120 minutes?– National Registry of Myocardial Infarction data show

trf-D2B = 180 minutes (median)– “Rural” = referral to receiving hospital

• >30 Miles apart (per MapQuest, etc)• >30 Minutes apart (per MapQuest, etc)

Prague-2 (N = 850)

106.8

15.2

8.4

0

2

4

6

8

10

12

14

16

SK PCI Trf SK PCI Trf

• Randomized-to-reperfusion start time (mean)

– Tissue plasminogen activator (TPA) = 12 minutes

– Trf-PCI = 97 minutes– PCI delay = 85 minutes

• Door to needle (D2N) = ?• D1B2 = ?

P = 0.12P = 0.003

30D Death 30D CEP

Widimsky P, et al. Eur Heart J. 2003;24:94–104.

DANAMI-2 (N = 1,129)Trf-PCI vs Lytics

14.2

8.5

0

2

4

6

8

10

12

14

16

TPA PCI Trf

• Randomized-to-reperfusion start time (median)– TPA = 20 minutes – Trf PCI = 90 minutes– PCI delay = 70 minutes

• ?D2N = 45 minutes?• ?D1B2 = 112 minutes?

30D Death-MI-CVA

P = 0.002

Two Recent Studiesof Transfer PCI

August 2007 in Circulation

2004–2006 Mayo Study (Rochester)

• Observational study, N = 597 STEMI• A (n = 258) PCI on-site at Mayo• 28 referral hospitals 30–90 minutes (57 median)

• B (n = 105) Trf-PCI for symptoms >3 hours• C (n = 131) Full-dose lytics for symptoms <3

hours, then routine transfer– 37% immediate rescue PCI– 63% routine angiogram/PCI in 1–2 days

• n = 63 STE mimics (10%), n =40 No PHI release

Ting H, et al. Circulation. 2007;116:729–736.

2004–2006 Mayo Study (Rochester)

Group Median

Time (minutes)

% Rate

Target

In-Hospital

Death*

Intracranial Hemorrhage

A=

PPCI

71 75%D2B <90 minutes

6.6% 0%

B=

Trf-PCI


5.7% 0%

C= Lytic

Rescue PCI

25 70% D2N <30 minutes

3.1% 2.3%

*N = 27 deaths total, and Group A with 5x rate of cardiogenic shock vs Group C

Ting H, et al. Circulation. 2007;116:729–736.

2003–2006 Minneapolis Study

• Level 1 Myocardial Infarction Registry with30 referral hospitals

• N = 1,345 consecutive STEMI patients– Including >10% shock, arrest, or age ≥80 years

• n = 297 PCI center at Abbott Northwestern

• n = 620 Trf-PCI Zone 1 (<60 miles)– ASA 325 mg, clopidogrel 600 mg, heparin 60 U/kg

• n = 396 Trf-PCI Zone 2 (60–210 miles)– Half-TNK + Zone 1 medications

Henry TD, et al. Circulation. 2007;116:721–728.

2003–2006 Minneapolis StudyGroup Median

Time (minutes)

% Rate

Target

In-Hospital

Death*

Intracranial Hemorrhage

On-site

PPCI


3.7% 0%

Zone 1

Trf-PCI

95 40%D1B2 <90 minutes

3.8% 0.2%

Zone 2Fac-PCI

120 15% D1B2 <90 minutes

5.2% 0.2%

*N = 57 deaths total, Zone 2 patients older and more renal insufficiency (CrCl <70 mL/min)


2003–2006 Minneapolis Study

N = 854 had one-year follow-up via SS Death Index

Zone 1 had 80% rate of D1B2 <120 minutes Trf-PCI

Zone 2 had 50% rate of D1B2 <120 minutes Trf-PCI with half-TNK


Summary of D2B Goals in 2007

• On-site PPCI D2B ≤90 minutes

• Urban Trf-PCI D2B ≤90 minutes

• ?Rural Trf-PCI D2B ≤120 minutes?– “Rural” = referral to receiving hospital

• >30 Miles apart (per MapQuest, etc)• >30 Minutes apart (per MapQuest, etc)

Judd E.“Italian

Stallion” Hollander, MD

JewishJewish

STEMI:Lytics vs PCI

Judd E. Hollander, MDProfessorClinical Research Director

Department of Emergency MedicineDepartment of Emergency Medicine

University of Pennsylvania Health SystemUniversity of Pennsylvania Health System

STEMI: Acute Therapy

General treatment measures

Antman EM, et al. Available at: http://www.acc.org/clinical/guidelines/stemi/index.pdf. Accessed November 1, 2005.

► AnalgesicsAnalgesics► NitratesNitrates► OxygenOxygen

► ββ-blockers (decrease heart rate)-blockers (decrease heart rate)

► Primary PCI or coronary thrombolysisPrimary PCI or coronary thrombolysis(primary PCI preferred after 3 hours)(primary PCI preferred after 3 hours)

► ASA (162–325 mg, acute dose) ASA (162–325 mg, acute dose) ► ClopidogrelClopidogrel► Heparin or enoxaparinHeparin or enoxaparin► GP IIb/IIIa inhibitorsGP IIb/IIIa inhibitors

Infarct sizelimitation

Reperfusion

Antithrombotic and antiplatelet therapy

Selection of Reperfusion Strategy

Fibrinolysis generally preferred

• Early presentation (≤3 hours from symptom onset and delay to invasive strategy)

• Invasive strategy not an option (cath lab not available, no vascular access, lack of skilled PCI lab)

• Delay to invasive strategy D2B — D2N >1 hour; median contact to balloon >90 minutes

Invasive strategy generally preferred• Skilled PCI lab available with surgical

backup (median contact to balloon <90 minutes)

• High risk from STEMI (cardiogenic shock, Killip class ≥3)

• Contraindication to lysis (including increased bleeding/intracerebral hemorrhage [ICH] risk)

• Late presentation (>3 hours)• Diagnosis in doubt

Antman EM, et al. Available at: www.acc.org/clinical/guidelines/stemi/index.pdf 2004.

8.57.3 7.2

22.0

2.0

7.24.9

2.8

6.8

1.0

0.0

5.0

10.0

15.0

20.0

25.0

Death DeathSHOCK

excl.

Reinfarction Recurrentischemia

Stroke

Per

cen

t (%

)

Lysis

PCI

8.57.3 7.2

22.0

2.0

7.24.9

2.8

6.8

1.0

0.0

5.0

10.0

15.0

20.0

25.0

Death DeathSHOCK

excl.


Stroke

Per

cen

t (%

)

Lysis

PCI

PCI vs Fibrinolysis:Systematic Overview

Short term (4–6 weeks)

Keeley EC, et al. Lancet. 2003;361:13–20.

P = 0.0002 P = 0.0003 P < 0.0001

P < 0.0001

P = 0.0004

(23 RCTs, N = 7,739)

RCT, randomized controlled trial.

Open Arteries & Mortality

4.6

87.9

15.7

0

2

4

6

8

10

12

14

16

TIMI 3 TIMI 0,1,2

Pat

ien

t M

ort

alit

y (%

) 30 d2 yr

Ross AM, et al. Circulation. 1998;97:1549–1556.

90 min TIMI Flow Postfibrinolytic

GUSTO-I (STK vs tPA) Angiographic Investigators: Postlytic TIMI Flow Predicts Mortality

Mortality by Time to Primary PCI

1.0%

3.7% 4.0%

6.4%

14.1%

0

5

10

15

<60 min 61–75 min 76–90 min >91 min Assigned toPCI, no cathperformed

Enrollment to balloon inflation

Pat

ien

t (%

)

1.0%

3.7% 4.0%

6.4%

14.1%

0

5

10

15

<60 min 61–75 min 76–90 min >91 min Assigned toPCI, no cathperformed

Enrollment to balloon inflation

Pat

ien

t (%

)

Adapted from Berger P, et al. Circulation. 1999;100:14–20.

P = 0.001

GUSTO-IIb

0

2

4

6

8

10

12

0 60 120 180 240 300 360

Ischemic time (min)

1 ye

ar m

ort

alit

y (%

)

0

2

4

6

8

10

12

0 60 120 180 240 300 360

Ischemic time (min)

1 ye

ar m

ort

alit

y (%

)

Symptom Onset to Treatment and1-Year Mortality: Primary PCI

The relative risk of 1-year mortality increases by 7.5% for each 30-minute delay

Circulation. 2004;109:1223–1225.

Y=2.86 (Y=2.86 (± 1.45) + 0.0045X± 1.45) + 0.0045X11 + 0.000043X + 0.000043X22

PP<.001<.001

Boersma E, et al. Lancet. 1996;348:771–775.

Time vs Outcome:50,246 Lytic Patients

0

Ab

solu

te B

enef

itp

er 1

,000

Tre

ated

Pat

ien

ts

0

20

40

60

80

3 6 9 12 15 18 21 24Time to Treatment

5.4%

7.3%

14.6%

0%

5%

10%

15%

< 2hr 2-4hr > 4hr

Sx Onset to Presentation Fibrinolysis

6-M

on

th M

ort

alit

y

5.4%

7.3%

14.6%

0%

5%

10%

15%

< 2hr 2-4hr > 4hr

Sx Onset to Presentation Fibrinolysis

6-M

on

th M

ort

alit

y

5.1%6.1% 6.7%

0%

5%

10%

15%

< 2hr 2-4hr > 4hr

Sx Onset to Presentation Primary Angioplasty

6-M

on

th M

ort

alit

y

5.1%6.1% 6.7%

0%

5%

10%

15%

< 2hr 2-4hr > 4hr

Sx Onset to Presentation Primary Angioplasty

6-M

on

th M

ort

alit

y

Presentation Delay vs Outcome

Zijlstra F, et al. Eur H eart J. 2002;23:550–557.

Mortality Rates with Primary PCI as a Function of PCI-Related Time Delay

P = 0.006

Circle sizes = sample size of the study

Solid line = weighted meta-regression

Nallamothu BK, Bates ER. Am J Cardiol. 2003;92:824–826.

62 min62 min BenefitFavors PCI

HarmFavors Lysis

For every 10-minute delay to PCI, 1% reduction in mortality difference toward lytics

5

10

15

0

Ab

solu

te R

isk

Dif

fere

nce

in

Dea

th (

%)

–50 20 40 60 80 100

PCI-related time delay (D2B – D2N)

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

alit

y

Pre-hosp tPAPCI

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

alit

y

Pre-hosp tPAPCI

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

alit

y

Lytic (SK)Transfer for 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

alit

y

Lytic (SK)Transfer for PCI

Early Presenting Patients: Primary PCI vs Fibrinolytics

P = 0.058P = 0.058 P = 0.47P = 0.47

CAPTIM

P < 0.02P < 0.02

PRAGUE-2Widimsky P, et al. Eur Heart J. 2003;24:94–104. Steg PG, et al. Circulation. 2003;108:2851–2856.

0

20

40

60

80

100

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999

Med

ian

tim

e, m

inu

tes

0

20

40

60

80

100

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999

Med

ian

tim

e, m

inu

tes

National Trends in AMI Management:Door to Drug Time with Thrombolysis

6060

9191

34343939

75th percentile, 5275th percentile, 52

25th percentile, 2225th percentile, 22

NRMI 1(Activase only)

NRMI 1(Activase only)

NRMI 2(All lytics)

NRMI 2(All lytics)

NRMI 3(All lytics)

NRMI 3(All lytics)

CRUSADE: Time from Presentation to Catheterization

• This analysis of the CRUSADE Registry looked at 56,352 patients with unstable angina or NSTEMI at 310 hospitals in the United States between January 2001 and September 2003

• Median time to cardiac catheterization (among patients who underwent the procedures):– Weekday patients: 23.4 hours (10.4 to 45.3 hours) – Weekend patients: 46.3 hours (21.4 to 63.5 hours), P < 0.0001

Ryan JW, et al. Circulation. 2005;112:3049–3057.

Hospital Hospital PresentationPresentation

23.4 hrs 46.3 hrs

Weekend Patients (n=10,804)

Weekday Patients (n=45,548)

0 24 48

Time to Catheterization

Primary PCI Outcomes:Working Hours vs Off Hours

3.8

6.9

1.9

4.2

0

1

2

3

4

5

6

7

8

0800–1800 h 1800–0800 h

Hospital admission

Per

cen

t

Failed PCI

30-day mortality

3.8

6.9

1.9

4.2

0

1

2

3

4

5

6

7

8

0800–1800 h 1800–0800 h

Hospital admission

Per

cen

t

Failed PCI

30-day mortality

Henriques JP, et al. J Am Coll Cardiol. 2003;41:2138–2142.

P P < 0.01< 0.01

P P < 0.01< 0.01

Zwolle Group, 1,702 STEMI patients: 1994–2000

PCI Availability in the United States

Jacobs AK, et al. Circulation. 2006;113:1159–1161.

100%

90%

80%

70%

60%

50%

40%

30%

20%

10%

0%

≈2,200 (44%)have cath labs

≈2,200 (44%)have cath labs

≈2,800 (56%) don’t have cath labs≈2,800 (56%) don’t have cath labs

≈1,200

(24% of total hospitals, 55% of hospitals with cath

labs)are capable of PCI

≈1,200

(24% of total hospitals, 55% of hospitals with cath

labs)are capable of PCI

Of the approximately 5,000 acute care hospitals in the United States:

Of the approximately 5,000 acute care hospitals in the United States:

Less than 25% of acute care hospitals in the United States have cath labs with PCI capabilities

Less than 25% of acute care hospitals in the United States have cath labs with PCI capabilities

Interhospital Transfer for PCIM

ort

alit

y (%

)

(n = 200) (n = 137) (n = 850) (n = 1,129)(n = 150)

6.7

1412.1

8.57

8.46.8 6.5

10

6.7

0

5

10

15

20

LIMI1 PRAGUE-12 AIR-PAMI3 PRAGUE-24 DANAMI5

On-site fibrinolysis Transfer for PCI

1. Vermeer F, et al. Heart. 1999;82:426–431.2. Widimsky P, et al. Eur Heart J. 2000;21:823–831.

3. Grines CL, et al. J Am Coll Cardiol. 2002;39:1713–1719. 4. Widimsky P, et al. Eur Heart J. 2003;24:94–104.

5. Andersen HR, et al. N Engl J Med. 2003;349:733–742.

Nallamothu BK, et al. Circulation. 2005;111:761–767.

STEMI: Transfer for PCI NRMI (1999–2002) 4,278 Patients

28.4>4 hours

55.42–4 hours

16.2<2 hours

4.2 <90 minutes

% of Patients D2B Time

NRMI, National Registry of Myocardial Infarction.

Institutional Characteristics

• PCI readiness– Time of day– Volume– D2B time

• EM readiness– Who is decision maker?– D2N time

• Collaborative relationships

Selection of Reperfusion Strategy

Fibrinolysis generally preferred

• Early presentation (≤3 hours from symptom onset and delay to invasive strategy)

• Invasive strategy not an option (cath lab not available, no vascular access, lack of skilledPCI lab)

• Delay to invasive strategy D2B — D2N >1 hour; median contact to balloon >90 minutes

Invasive strategy generally preferred• Skilled PCI lab available with surgical

backup (median contactto balloon <90 minutes)

• High risk from STEMI(cardiogenic shock, Killipclass ≥3)

• Contraindication to lysis(including increased bleeding/ICH risk)

• Late presentation (>3 hours)• Diagnosis in doubt

Antman EM, et al. Available at: www.acc.org/clinical/guidelines/stemi/index.pdf 2004.

The Rock Rokos

If D2B >90 minutes anticipated…

Can lytics be used to extend reperfusion window involving PPCI?

Facilitated PCI for all STEMI

Full lytics, then PPCI within 1–3 hours

No ASSENT-4 showed 2x rate of in-hospital death with TNK + PCI vs PCI alone

Half-lytics + glycoprotein inhibitors

?No FINESSE September 07; efficacy is same, but bleeding

Half-TNK +

clopidogrel 600 mg

?Yes Minneapolis Zone 2 patients with Trf 60–210 miles and 50% rate of D1B2 <120 minutes

Rescue PCI

• Validated in REACT trial• Initial full-dose lytics, then rescue PCI only

for failed reperfusion– 30%–40% fail lytics and need rescue PCI– Defined as <50% ST-resolution after 90

minutes in the lead with prior maximal ST-elevation

– ??Rescue PCI comparable to PPCI on-site at Mayo??

Gershlick AH, et al. N Engl J Med. 2005;353:2758–2768.

0 20 40 60 80 100

PCI-Related Time Delay (D2B – D2N)

Mortality Rates With PPCI as a Function of PCI-Related Time Delay

P = 0.006

Ab

solu

te R

isk

Dif

fere

nce

in D

eath

(%

)A

bso

lute

Ris

k D

iffe

ren

ce in

Dea

th (

%)

N = 7,419 from Keeley & Grines meta-analysis

Nallamothu BK, Bates ER. Am J Cardiol. 2003;92:824–826.

62 min62 min

PCI BetterPCI Better

Lytics BetterLytics Better

For every 10-minute delay to PCI: 1% reduction in mortality difference toward lytics

15

10

5

0

-5

Acceptable PCI Delay Varies

• Factors affecting PCI delay

– Age– Myocardial

infarction location– Symptom duration

Pinto DS, et al. Circulation. 2006;114:2019–2025.

Clinician’s PerspectiveThe need for speed…consistently

Academic Komodo Dragon

Unable to make a clean kill today, because current data on Trf-PCI vs

lytics are just NOT definitive

Can We Improve STEMI Care with Fibrinolysis?

Where did they find this guy anyway?

Department of Emergency MedicineDepartment of Emergency Medicine

University of Pennsylvania Health SystemUniversity of Pennsylvania Health System

8.57.3 7.2

22.0

2.0

7.24.9

2.8

6.8

1.0

0.0

5.0

10.0

15.0

20.0

25.0

Death DeathSHOCK

excl.


Stroke

Per

cen

t (%

)

Lysis

PCI

8.57.3 7.2

22.0

2.0

7.24.9

2.8

6.8

1.0

0.0

5.0

10.0

15.0

20.0

25.0

Death DeathSHOCK

excl.


Stroke

Per

cen

t (%

)

Lysis

PCI

PCI vs FibrinolysisSystematic Overview

Short term (4-6 weeks)


P = 0.0002P = 0.0002P = 0.0003P = 0.0003 P < 0.0001P < 0.0001

P < 0.0001P < 0.0001

P = 0.0004P = 0.0004

(23 RCTs, n = 7,739) (23 RCTs, n = 7,739)

Adjunctive Medications:Without Effect on Mortality

• Double-bolus tPA• TNK• Recombinant plasminogen

activator (rPA)• Novel plasminogen

activator (nPA)• GP IIb/IIIa inhibition + lytic• Oral GP IIb/IIIa

• Bivalirudin• Hirudin• Pexelizumab• Magnesium• Adenosine• PSGL• GIK

etc….

USEFUL ADJUNCTSAspirin

EnoxaparinClopidogrel

CLARITY–TIMI 28Double-Blind, Randomized, Placebo-Controlled Trial in

3,491 Patients, Aged 18–75 Years, with STEMI <12 Hours

Fibrinolytic, ASA, heparin

Clopidogrel300 + 75 mg every day

Coronary angiogram(2–8 days)

Primary end pointOccluded artery (TIMI flow grade 0/1) or death/MI by time of angiography

Randomized

Placebo

Studydrug

30-day clinical follow-up

Open-labelclopidogrelper MD in

both groups

Sabatine MS, et al. N Engl J Med. 2005;352:1179–1189.

CLARITY–TIMI 28: Primary End Point: Occluded Artery (or Death/MI Until Angiography/HD)

PlaceboClopidogrel

P = 0.001

Odds Ratio: 0.64(95% CI, 0.53–0.76)

1.00.4 0.6 0.8 1.2 1.6

ClopidogrelBetter

PlaceboBetter

N = 1,752 N = 1,739

36%Odds Reduction

36%Odds Reduction

15.0

21.7

Occ

lud

ed A

rter

y o

r D

eath

/MI

(%)

0

5

10

15

20

25


CLARITY–TIMI 28: Cardiovascular Disease, Myocardial Infarction, Recurrent Ischemic Urgent

Revascularization

Days

En

d P

oin

t (%

)

0

5

10

15

0 5 10 15 20 25 30

Placebo

Clopidogrel

Odds Ratio: 0.80(95% CI, 0.65–0.97)

P = 0.03

20%


ASSENT-3

ST-Segment Elevation AMI(6,095 patients)

Randomized

150-325 mg Aspirin (daily)

Half-Dose TNK-tPA

Plus AbciximabPlus Low-Dose

Heparin2,017 Patients

Full-Dose TNK-tPAPlus Weight-

AdjustedHeparin

2,038 Patients

Full-Dose TNK-tPAPlus

Enoxaparin2,040 Patients

ASSENT-3 Investigators. Lancet. 2001;358:605–613.

11.4%

11.1%

15.4% 13.8

%

14.2%

17.0%

0

5

10

15

20

Perc

en

t

Death/MI/Reischemia Primary End Point & ICH/Major Bleed

EnoxaparinAbciximabUFH

3-way P valuesP = 0.0001 P = 0.0081

ASSENT-3: Results

ASSENT-3 Investigators. Lancet. 2001;358:605–613.UFH, unfractionated heparin.

STEMI <6 hoursLytic eligible

Lytic choice by MD(TNK, tPA, rPA, SK)

ENOX

<75 y: 30 mg IV bolus SC 1.0 mg/kg every 12 hours (Hosp DC)

≥75 y: No bolusSC 0.75 mg/kg every 12 hours (Hosp DC)

CrCl <30 mL/min: 1.0 mg/kg every 24 hours

Double-blind, double-dummy

ASA

Day 30Primary efficacy end point: death or nonfatal MI

Primary safety end point: TIMI major hemorrhage

EXTRACT-TIMI 25

UFH60 U/kg bolus (4000 U) Inf 12 U/kg/h (1000 U/h)

Duration: at least 48 hoursContinued at MD discretion

Primary End Point (Intent to Treat): Death or Nonfatal MI

0

3

6

9

12

15

0 5 10 15 20 25 30

Pri

ma

ry E

nd

Po

int

(%)

ENOX

UFH

Relative Risk0.83 (0.77 to 0.90)

P < 0.0001

Days

9.9%

12.0%

Lost to follow-up = 3

17% RRR

Death or Nonfatal MI: Day 30Medical Rx vs Any PCI

0.00040.001

% E

ven

ts

0

5

10

15

Any PCI Medical Rx

n = 15,223 (75%) n = 4,676 (23%)

ENOX

UFH

9.7

RRR 16%

11.413.8

10.7

RRR 23%

P Value

Death or Nonfatal MI: Day 30Clopidogrel Use

0.0005 0.0006

% E

ven

ts

0

5

10

15

No Clopidogrel Clopidogrel Use*

n = 14,752 (78%) n = 5,727 (28%) P Value

10.4

RRR15%

12.211.4

8.7

RRR24%

*2,546 clopidogrel-treated patients did not undergo PCI.

ENOX

UFH

Net Clinical Benefit: 30 Days

11 1.250.90.8

Death or Nonfatal MI or Nonfatal ICH

Death or Nonfatal MI or Nonfatal Major Bleed

Death or Nonfatal MI or Nonfatal Disabl. Stroke

ENOX BetterENOX Better UFH BetterUFH BetterRR

UFH (%) ENOX (%) RRR (%)

12.3 10.1 18

12.8 11.0 14

12.2 10.1 17

Prespecified Definitions

P < 0.0001

P < 0.0001

P < 0.0001

Trial Results in Perspective:PCI vs Lysis for STEMI

7

2.2

3.4

0

2

4

6

8

10

% E

ven

ts (

30–

42

Da

ys)

Reinfarction

Lytic Arms (UFH)

PCI Arms

ENOX

Overview of 23 RCTs


Conclusions

• There is still a role for fibrinolytic therapy in STEMI

• Adjuvant clopidogrel and/or enoxaparin improve outcomes in combination with fibrinolytics

ConclusionThe cardiologist can stay home

Conclusion…and in bed

Conclusion…and patients don’t need to be subjected to the extra risk of transfers

Facilitated PCI: Use of Lytics in the ED Delayed PCI “The Rock Rokos” Lytics “Italian Stallion...

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