Transcript Slide 1

Facilitated PCI: Use of Lytics
in 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 to
on-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 Fibrinolytics
Where 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
Odds of in-hospital mortality
1.8
1.6
1.4
1.2
1
0.8
0.6
0.4
0.2
0
In-hospital mortality regardless of
symptom onset or risk
8
7
P < 0.001
6
P < 0.001
5
4
3
2
1
0
<60 61- 91- 121- 15190 120 150 180
Cannon CP, et al. JAMA. 2000;283:2941–2947.
<90
91120
121- >150
150
McNamara RL, et al. J Am Coll Cardiol.
2006;47:2180–2186.
D2B Alliance GOAL:
≥75% rate of D2B ≤90 Min
1.
2.
3.
4.
5.
6.
Emergency physician activates the cath lab
One call activates the cath lab
Cath lab team ready in 20–30 minutes
Prompt data feedback
Senior management commitment
Team-based approach
Optional = Prehospital electrocardiogram to activate
the cath lab
D2B Zones for PPCI in STEMI
• <90 Minutes  GREEN zone
• 90–120 Minutes  YELLOW
zone
• >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
• <90 Minutes  GREEN zone
• 90–120 Minutes  YELLOW
zone
• >120 Minutes  RED zone
 YELLOW zone
ACEP 2006 Clinical Policy
Recommendations
• What are the indications for fibrinolytics in
patients being treated at or transferred to a
PCI center?
• Level A = None
• Level B = Lytics for STEMI <3 hours after
symptom onset and expected D2B exceeding
90 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 prey
on 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)
• Randomized-toreperfusion start time
(mean)
16
14
12
P = 0.003
10
P = 0.12
8
6
4
15.2
10
8.4
6.8
2
0
SK
PCI Trf
30D Death
SK
PCI Trf
30D CEP
– Tissue plasminogen
activator (TPA) = 12
minutes
– Trf-PCI = 97 minutes
– PCI delay = 85 minutes
• Door to needle (D2N) = ?
• D1B2 = ?
Widimsky P, et al. Eur Heart J. 2003;24:94–104.
DANAMI-2 (N = 1,129)
Trf-PCI vs Lytics
16
14
12
P = 0.002
10
8
6
14.2
8.5
4
2
0
TPA
PCI Trf
30D Death-MI-CVA
• Randomized-toreperfusion start time
(median)
– TPA = 20 minutes
– Trf PCI = 90 minutes
– PCI delay = 70 minutes
• ?D2N = 45 minutes?
• ?D1B2 = 112 minutes?
Two Recent Studies
of 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%
6.6%
0%
5.7%
0%
3.1%
2.3%
B=
Trf-PCI
C= Lytic
Rescue PCI
D2B <90
minutes
116
12%
D2B <90
minutes
25
70% D2N
<30 minutes
*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 with
30 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 Study
Group
Median
Time
(minutes)
% Rate
Target
In-Hospital
Death*
Intracranial
Hemorrhage
On-site
PPCI
65
80%
3.7%
0%
Zone 1
Trf-PCI
95
3.8%
0.2%
Zone 2
120
5.2%
0.2%
Fac-PCI
D2B <90
minutes
40%
D1B2 <90
minutes
15% D1B2
<90 minutes
*N = 57 deaths total, Zone 2 patients older and more renal insufficiency
(CrCl <70 mL/min)
Henry TD, et al. Circulation. 2007;116:721–728.
2003–2006 Minneapolis Study
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
N = 854 had one-year follow-up via
SS Death Index
Henry TD, et al. Circulation. 2007;116:721–728.
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.
Jewish
“Italian
Stallion”
Hollander, MD
STEMI:
Lytics vs PCI
Judd E. Hollander, MD
Professor
Clinical Research Director
Department of Emergency Medicine
University of Pennsylvania Health System
STEMI: Acute Therapy
General treatment
measures
►
Analgesics
► Nitrates
► Oxygen
Infarct size
limitation
►
Reperfusion
►
Antithrombotic
and antiplatelet
therapy
β-blockers (decrease heart rate)
Primary PCI or coronary thrombolysis
(primary PCI preferred after 3 hours)
► ASA (162–325 mg, acute dose)
► Clopidogrel
► Heparin or enoxaparin
► GP IIb/IIIa inhibitors
Antman EM, et al. Available at: http://www.acc.org/clinical/guidelines/stemi/index.pdf. Accessed November 1, 2005.
Selection of Reperfusion
Strategy
Fibrinolysis generally
preferred
Invasive strategy 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
• 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.
PCI vs Fibrinolysis:
Systematic Overview
(23 RCTs, N = 7,739)
Short term (4–6 weeks)
P < 0.0001
25.0
Percent (%)
20.0
15.0
10.0
22.0
Lysis
PCI
P = 0.0002
8.5
7.2
P = 0.0003
P < 0.0001
7.3
7.2
6.8
4.9
5.0
2.8
P = 0.0004
2.0 1.0
0.0
Death
RCT, randomized controlled trial.
Death
SHOCK
excl.
Reinfarction
Recurrent
ischemia
Stroke
Keeley EC, et al. Lancet. 2003;361:13–20.
Open Arteries & Mortality
GUSTO-I (STK vs tPA) Angiographic Investigators:
Postlytic TIMI Flow Predicts Mortality
15.7
Patient Mortality (%)
16
30 d
2 yr
14
12
10
7.9
8
8
6
4.6
4
2
0
TIMI 3
TIMI 0,1,2
90 min TIMI Flow Postfibrinolytic
Ross AM, et al. Circulation. 1998;97:1549–1556.
Mortality by Time to Primary PCI
P = 0.001
14.1%
15
Patient (%)
GUSTO-IIb
10
6.4%
5
3.7%
4.0%
61–75 min
76–90 min
1.0%
0
<60 min
>91 min
Assigned to
PCI, no cath
performed
Enrollment to balloon inflation
Adapted from Berger P, et al. Circulation. 1999;100:14–20.
Symptom Onset to Treatment and
1-Year Mortality: Primary PCI
1 year mortality (%)
The relative risk of 1-year mortality increases
12
by 7.5% for each 30-minute delay
10
8
6
4
Y=2.86 (± 1.45) + 0.0045X1 + 0.000043X2
P<.001
2
0
0
60
120
180
240
300
360
Ischemic time (min)
Circulation. 2004;109:1223–1225.
Time vs Outcome:
50,246 Lytic Patients
Absolute Benefit
per 1,000 Treated Patients
80
60
40
20
0
0
3
6
9
12
15
Time to Treatment
18
21
24
Boersma E, et al. Lancet. 1996;348:771–775.
Presentation Delay vs Outcome
14.6%
15%
10%
5.1%
6.1%
6.7%
5%
6-Month Mortality
6-Month Mortality
15%
10%
7.3%
5.4%
5%
0%
0%
< 2hr
2-4hr
> 4hr
Sx Onset to Presentation
Primary Angioplasty
< 2hr
2-4hr
> 4hr
Sx Onset to Presentation
Fibrinolysis
Zijlstra F, et al. Eur H eart J. 2002;23:550–557.
Absolute Risk Difference in Death (%)
Mortality Rates with Primary PCI as a
Function of PCI-Related Time Delay
15
Circle sizes = sample size of the study
Solid line = weighted meta-regression
10
P = 0.006
5
Benefit
Favors PCI
62 min
0
Harm
Favors Lysis
–5
0
20
40
60
80
PCI-related time delay (D2B – D2N)
100
For every 10-minute delay to PCI, 1% reduction in mortality difference toward lytics
Nallamothu BK, Bates ER. Am J Cardiol. 2003;92:824–826.
Early Presenting Patients:
Primary PCI vs Fibrinolytics
10%
15.3%
15%
10%
P < 0.02
7.4% 7.3%
6.0%
5%
0%
30-day mortality
30-day mortality
20%
Lytic (SK)
Transfer for PCI
8%
6%
Pre-hosp tPA
PCI
P = 0.058
5.7%
P = 0.47
5.9%
3.7%
4%
2.2%
2%
0%
<3 Hrs
(n=551)
>3 Hrs
(n=299)
PRAGUE-2
<2 Hrs
(n=460)
>2 Hrs
(n=374)
CAPTIM
Widimsky P, et al. Eur Heart J. 2003;24:94–104.
Steg PG, et al. Circulation. 2003;108:2851–2856.
National Trends in AMI Management:
Door to Drug Time with Thrombolysis
Median time, minutes
100
NRMI 1
(Activase only)
NRMI 2
(All lytics)
NRMI 3
(All lytics)
91
80
60
40
60
75th percentile, 52
39
34
20
25th percentile, 22
0
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
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
23.4 hrs
Hospital
Presentation
0
46.3 hrs
Weekday Patients
Weekend Patients
(n=45,548)
(n=10,804)
24
48
Time to Catheterization
Ryan JW, et al. Circulation. 2005;112:3049–3057.
Primary PCI Outcomes:
Working Hours vs Off Hours
Zwolle Group, 1,702 STEMI patients: 1994–2000
8
7
Failed PCI
30-day mortality
6.9
P < 0.01
Percent
6
5
4
3
2
4.2
3.8
P < 0.01
1.9
1
0
0800–1800 h
1800–0800 h
Hospital admission
Henriques JP, et al. J Am Coll Cardiol. 2003;41:2138–2142.
PCI Availability in the United States
Of the approximately 5,000 acute care hospitals in
the United States:
100%
90%
80%
70%
≈2,800 (56%)
don’t have cath labs
60%
50%
40%
≈2,200 (44%)
30%
have cath labs
20%
≈1,200
10%
(24% of total hospitals,
55% of hospitals with cath
labs)
0%
are capable of PCI
Less than 25% of acute care
hospitals in the United States
have cath labs with PCI
capabilities
Jacobs AK, et al. Circulation. 2006;113:1159–1161.
Interhospital Transfer for PCI
Mortality (%)
20
On-site fibrinolysis
Transfer for PCI
14
15
12.1
10
10
6.7 6.7
7
8.5
8.4
6.8
6.5
5
0
LIMI1
(n = 150)
PRAGUE-12
AIR-PAMI3
(n = 200)
(n = 137)
PRAGUE-24
(n = 850)
DANAMI5
(n = 1,129)
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.
STEMI: Transfer for PCI
NRMI (1999–2002) 4,278 Patients
D2B Time
% of Patients
<90 minutes
4.2
<2 hours
16.2
2–4 hours
55.4
>4 hours
28.4
NRMI, National Registry of Myocardial Infarction.
Nallamothu BK, et al. Circulation. 2005;111:761–767.
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
Invasive strategy 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
• 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/
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 +
?Yes
clopidogrel 600 mg
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 STelevation
– ??Rescue PCI comparable to PPCI on-site
at Mayo??
Gershlick AH, et al. N Engl J Med. 2005;353:2758–2768.
Absolute Risk Difference in Death (%)
Mortality Rates With PPCI as a
Function of PCI-Related Time Delay
15
N = 7,419 from Keeley &
Grines meta-analysis
PCI
Better
10
P = 0.006
5
62 min
0
-5
Lytics
Better
0
20
40
60
80
100
PCI-Related Time Delay (D2B – D2N)
For every 10-minute delay to PCI: 1% reduction in mortality difference toward lytics
Nallamothu BK, Bates ER. Am J Cardiol. 2003;92:824–826.
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 Perspective
The 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?
Department of Emergency Medicine
University of Pennsylvania Health System
Where did they find this guy anyway?
PCI vs Fibrinolysis
Systematic Overview
Short term (4-6 weeks)
(23 RCTs, n = 7,739)
P < 0.0001
25.0
Percent (%)
20.0
15.0
10.0
22.0
Lysis
PCI
P = 0.0002
8.5
7.2
P = 0.0003
P < 0.0001
7.3
7.2
6.8
4.9
5.0
2.8
P = 0.0004
2.0 1.0
0.0
Death
Death
SHOCK
excl.
Reinfarction
Recurrent
ischemia
Stroke
Keeley EC, et al. Lancet. 2003;361:13–20.
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
•
•
•
•
•
•
•
USEFUL ADJUNCTS
Aspirin
Enoxaparin
Clopidogrel
Bivalirudin
Hirudin
Pexelizumab
Magnesium
Adenosine
PSGL
GIK
etc….
CLARITY–TIMI 28
Double-Blind, Randomized, Placebo-Controlled Trial in
3,491 Patients, Aged 18–75 Years, with STEMI <12 Hours
Fibrinolytic, ASA, heparin
Randomized
Clopidogrel
300 + 75 mg every day
Placebo
Study
drug
Coronary angiogram
(2–8 days)
Open-label
clopidogrel
per MD in
both groups
30-day clinical follow-up
Primary end point
Occluded artery
(TIMI flow grade
0/1) or death/MI
by time of
angiography
Sabatine MS, et al. N Engl J Med. 2005;352:1179–1189.
Occluded Artery or Death/MI (%)
CLARITY–TIMI 28: Primary End Point:
Occluded Artery (or Death/MI Until Angiography/HD)
25
36%
Odds Reduction
21.7
Odds Ratio: 0.64
(95% CI, 0.53–0.76)
20
P = 0.001
15.0
15
10
5
0.4
0
N = 1,752
Clopidogrel
N = 1,739
0.6
0.8 1.0 1.2
Clopidogrel
Better
1.6
Placebo
Better
Placebo
Sabatine MS, et al. N Engl J Med. 2005;352:1179–1189.
CLARITY–TIMI 28: Cardiovascular Disease,
Myocardial Infarction, Recurrent Ischemic  Urgent
Revascularization
15
End Point (%)
Placebo
20%
Clopidogrel
10
Odds Ratio: 0.80
(95% CI, 0.65–0.97)
P = 0.03
5
0
0
5
10
20
15
25
30
Days
Sabatine MS, et al. N Engl J Med. 2005;352:1179–1189.
ASSENT-3
ST-Segment Elevation AMI(6,095 patients)
150-325 mg Aspirin (daily)
Randomized
Full-Dose TNK-tPA
Plus Enoxaparin
2,040 Patients
Half-Dose TNK-tPA
Plus Abciximab
Plus Low-Dose
Heparin
2,017 Patients
Full-Dose TNK-tPA
Plus Weight-Adjusted
Heparin
2,038 Patients
ASSENT-3 Investigators. Lancet. 2001;358:605–613.
ASSENT-3: Results
20
Enoxaparin
Abciximab
UFH
17.0%
Percent
15
10
3-way P values
P = 0.0001
P = 0.0081
15.4%
13.8%
11.4%
14.2%
11.1%
5
0
Death/MI/Reischemia
UFH, unfractionated heparin.
Primary End Point & ICH/Major Bleed
ASSENT-3 Investigators. Lancet. 2001;358:605–613.
EXTRACT-TIMI 25
STEMI <6 hours
Lytic eligible
ASA
Lytic choice by MD
(TNK, tPA, rPA, SK)
Double-blind, double-dummy
ENOX
<75 y: 30 mg IV bolus
SC 1.0 mg/kg every 12 hours (Hosp DC)
≥75 y: No bolus
SC 0.75 mg/kg every 12 hours (Hosp DC)
CrCl <30 mL/min: 1.0 mg/kg every 24 hours
UFH
60 U/kg bolus (4000 U)
Inf 12 U/kg/h (1000 U/h)
Duration: at least 48 hours
Continued at MD discretion
Day 30
Primary efficacy end point: death or nonfatal MI
Primary safety end point: TIMI major hemorrhage
Primary End Point (Intent to Treat):
Death or Nonfatal MI
Primary End Point (%)
15
UFH
12
12.0%
17% RRR
9
9.9%
ENOX
Relative Risk
0.83 (0.77 to 0.90)
P < 0.0001
6
3
Lost to follow-up = 3
0
0
5
10
15
Days
20
25
30
Death or Nonfatal MI: Day 30
Medical Rx vs Any PCI
13.8
15
% Events
11.4
10
5
10.7
9.7
RRR
23%
RRR
16%
ENOX
0
P Value
UFH
Any PCI
Medical Rx
n = 4,676 (23%)
n = 15,223 (75%)
0.001
0.0004
Death or Nonfatal MI: Day 30
Clopidogrel Use
% Events
15
12.2
11.4
10
5
10.4
8.7
RRR
15%
RRR
24%
ENOX
0
No Clopidogrel
P Value
UFH
Clopidogrel Use*
n = 14,752 (78%) n = 5,727 (28%)
0.0005
0.0006
*2,546 clopidogrel-treated patients did not undergo PCI.
Net Clinical Benefit: 30 Days
Prespecified Definitions
Death or Nonfatal MI or
Nonfatal Disabl. Stroke
Death or Nonfatal MI or
Nonfatal Major Bleed
Death or Nonfatal MI or
Nonfatal ICH
UFH (%) ENOX (%) RRR (%)
12.3
10.1
18
12.8
11.0
14
12.2
10.1
17
P < 0.0001
P < 0.0001
P < 0.0001
0.8
0.9
ENOX Better
1
RR
1.25
UFH Better
Trial Results in Perspective:
PCI vs Lysis for STEMI
Overview of 23 RCTs
(30–42 Days)
% Events
10
8
7
6
4
2
0
Lytic
Arms
(UFH)
3.4
2.2
PCI
Arms
ENOX
Reinfarction
Keeley EC, et al. Lancet. 2003;361:13–20.
Conclusions
• There is still a role for fibrinolytic
therapy in STEMI
• Adjuvant clopidogrel and/or
enoxaparin improve outcomes in
combination with fibrinolytics
Conclusion
The cardiologist can stay home
Conclusion
…and in bed
Conclusion
…and patients don’t need to be subjected
to the extra risk of transfers