facilitated pci: use of lytics in the ed delayed pci “the rock rokos” lytics “italian stallion...
Post on 14-Jan-2016
228 Views
Preview:
TRANSCRIPT
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
irokos@earthlink.net
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
• <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 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
116 12%D2B <90 minutes
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
65 80%D2B <90 minutes
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)
Henry TD, et al. Circulation. 2007;116:721–728.
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
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.“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.
Reinfarction Recurrentischemia
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.
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.
Reinfarction Recurrentischemia
Stroke
Per
cen
t (%
)
Lysis
PCI
PCI vs FibrinolysisSystematic Overview
Short term (4-6 weeks)
Keeley EC, et al. Lancet. 2003;361:13–20.
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
Sabatine MS, et al. N Engl J Med. 2005;352:1179–1189.
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%
Sabatine MS, et al. N Engl J Med. 2005;352:1179–1189.
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
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
ConclusionThe cardiologist can stay home
Conclusion…and in bed
Conclusion…and patients don’t need to be subjected to the extra risk of transfers
top related