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F. Van de Werf, ACC 2013
STREAMSTRATEGIC REPERFUSION EARLY AFTER
MYOCARDIAL INFARCTION
F. Van de Werf, ACC 2013
• Study grant from Boehringer Ingelheim to perform the STREAM trial, paid to the University of Leuven, Belgium
• Honoraria from Boehringer Ingelheim for membership of advisory board related to studies with dabigatran in patients with mechanical heart valves
Frans Van de Werf: Disclosures
F. Van de Werf, ACC 2013
• Large contemporary international registries continue to demonstrate persisting delays to primary PCI in STEMI patients first presenting to EMS or non-cath capable hospitals
• Subsequent transfer for primary PCI commonly results in reperfusion times exceeding current guideline recommendations
• These delays are associated with commensurate increases in morbidity and mortality
BACKGROUND
F. Van de Werf, ACC 2013
A strategy of early fibrinolysis followed by coronary angiography within 6-24 hours or rescue PCI if needed was compared with standard primary PCI
in STEMI patients with at least 2 mm ST-elevation in 2 contiguous leads
presenting within 3 hours of symptom onset and unable to undergo primary PCI within 1 hour.
STUDY AIM
F. Van de Werf, ACC 2013
SAMPLE SIZE AND STATISTICAL ANALYSES
•1000 patients per group was planned•Primary endpoint in PPCI group projected to be 15.0%•No formal primary hypothesis / all analyses explorative•Data reported on ITT basis with 95% CI•Analysis performed independently KU Leuven, Belgium
F. Van de Werf, ACC 2013
no lyticno lytic
STUDY PROTOCOL
RANDOMIZATION 1:1 by IVRS, OPEN LABELRANDOMIZATION 1:1 by IVRS, OPEN LABEL
Primary endpoint: composite of all cause death or shock or CHF or reinfarction up to day 30Primary endpoint: composite of all cause death or shock or CHF or reinfarction up to day 30
ECG at 90 min: ST resolution ≥ 50%ECG at 90 min: ST resolution ≥ 50%
Standard primary PCI Standard primary PCI
Aspirin Clopidogrel:
LD 300 mg + 75 mg QDEnoxaparin:
30 mg IV + 1 mg/kg SC Q12h
Aspirin Clopidogrel:
LD 300 mg + 75 mg QDEnoxaparin:
30 mg IV + 1 mg/kg SC Q12h
Antiplatelet andantithrombin treatment
according to local standards
Antiplatelet andantithrombin treatment
according to local standards
angio >6 to 24 hrsPCI/CABG if indicated
angio >6 to 24 hrsPCI/CABG if indicated
immediate angio + rescue PCI if indicated
immediate angio + rescue PCI if indicated
YES NO
Strategy A: pharmaco-invasiveStrategy A: pharmaco-invasive Strategy B: primary PCIStrategy B: primary PCI
AspirinClopidogrel:
75 mg QDEnoxaparin:
0.75 mg/kg SC Q12h
AspirinClopidogrel:
75 mg QDEnoxaparin:
0.75 mg/kg SC Q12h
STEMI <3 hrs from onset symptoms, PPCI <60 min not possible, 2 mm ST-elevation in 2 leads STEMI <3 hrs from onset symptoms, PPCI <60 min not possible, 2 mm ST-elevation in 2 leads
≥75y: ½ dose TNK≥75y: ½ dose TNK<75y:full dose<75y:full doseAfter 20% of the planned
recruitment, the TNK dose was reduced by 50% among patients ≥75 years of age.
F. Van de Werf, ACC 2013
ENROLMENT AND KEY DATES
• 1892 patients randomizedby 99 sites in 15 countries
• First patient in: March 19, 2008
• Last patient in: July 26, 2012
• Last patient out: Sep 7, 2012
Enrolment setting
F. Van de Werf, ACC 2013
PATIENTS PER COUNTRY
F. Van de Werf, ACC 2013
BASELINE CHARACTERISTICS (1)
Data are mean (SD) or %
F. Van de Werf, ACC 2013
BASELINE CHARACTERISTICS (2)
Data are %
F. Van de Werf, ACC 2013
62
Sx onset1st Medical
contact
61
1 Hour 2 Hoursn=1892
29
Randomize IVRS
9
Rx TNK
31 86
Sx onsetRx PPCI
100 min
178 min
MEDIAN TIMES TO TREATMENT (min)
1st Medical contact
78 min differenceRandomize IVRS
F. Van de Werf, ACC 2013
62
Sx onset
61
1 Hour 2 Hours
29 9
Rx TNK
31 86
Sx onsetRx PPCI
100 min
178 min
MEDIAN TIMES TO TREATMENT (min)
36% Rescue PCI at 2.2h
n=1892
64% non-urgent cath at 17h
1st Medical contact
Randomize IVRS
1st Medical contact Randomize IVRS
F. Van de Werf, ACC 2013
TIMI FLOW RATES
TIMI before PCI TIMI after PCI
P<0.001 P=0.41
F. Van de Werf, ACC 2013
INVASIVE PROCEDURES
F. Van de Werf, ACC 2013
PRIMARY ENDPOINT
TNK 12.4%
PPCI 14.3%
TNK vs PPCIRelative Risk 0.86, 95%CI (0.68-1.09)
p=0.24
Dth
/Sho
ck/C
HF/
ReM
I (%
)
The 95% CI of the observed incidence in the pharmaco-invasive arm would exclude a 9% relative excess compared with PPCI
F. Van de Werf, ACC 2013
SINGLE ENDPOINTS UP TO 30 DAYS
F. Van de Werf, ACC 2013
>
Subgroup analyses for primary endpoint within 30 daysRelative Risk (95%CI)
OVERALL
Age <75 years ≥75 years
P(interaction)
0.63
0.81
0.71
0.16
0.23
0.06
Time to randomization 0 to <2h ≥2h
MaleFemale
Systolic blood pressure <100 mmHg 100 to <140 mmHg 140 to <160 mmHg ≥160 mmHg
Killip class I II-IV
Anterior MIInferior MIOther MI
TNK Better PPCI Better
F. Van de Werf, ACC 2013
Subgroup analyses for primary endpoint within 30 days
Relative Risk (95%CI)Hypertension, Yes
P(interaction)0.34
0.24
0.68
0.13
Diabetes, Yes No
Place of randomization, Ambulance Community hospital
Before Amendment
TNK Better PPCI Better
>
>
No
Weight, <60 kg 60 to <90 kg ≥90 kg
TIMI Risk Score, <5 points ≥5 points
After Amendment
0.35
0.71
p=0.07
F. Van de Werf, ACC 2013
STROKE RATES
F. Van de Werf, ACC 2013
IN-HOSPITAL BLEEDING COMPLICATIONS
F. Van de Werf, ACC 2013
CONCLUSIONS
A strategy of fibrinolysis with bolus tenecteplase and contemporary antithrombotic therapy given before transport to a PCI-capable hospital coupled with timely coronary angiography :
circumvents the need for an urgent procedure in about two thirds of fibrinolytic treated STEMI patients.is associated with a small increased risk of intracranial bleeding.is as effective as primary PCI in STEMI patients presenting within 3 hours of symptom onset who cannot undergo primary PCI within one hour of first medical contact.
F. Van de Werf, ACC 2013
F. Van de Werf, ACC 2013
ACKNOWLEDGEMENTS
Statistical Analysis Committee
E. Lesaffre
K. Bogaerts
A. Belmans
G. Kalema
E. Bluhmki
Executive Committee
F Van de Werf
P. Armstrong
A. Gershlick
P. Goldstein
R. Wilcox
Boehringer-Ingelheim
T. Danays
E. Bluhmki
A. Regelin
G. Goetz
DSMB
K. Fox
G. Montalescot
C. Pollack
J. Tijssen
W. Weaver
R. Brower
Operations team
A. Regelin
T. Danays
E. Bluhmki
G. Goetz
R. Delbé
U. Fehse
K. Vandenberghe
C. Luys
K. Broos
K. Bogaerts
T. Temple
L. Merlini
M. Mazzoleni
M. Marangione
Steering Committee
K. Huber W. Schreiber
P. Sinnaeve P. Meert
L. Piegas A. Carvalho
R. Welsh F. Rosell
G. Steg Y. Lambert
U. Zeymer H. Arntz
J. Nanas M. Ostojic
C. Fresco A. Pesenti
L. Aaberge S. Halvorsen
S. Grajek V. Sulimov
J. KendallT. Quinn
J Adgey
ECG Core Lab
P. Armstrong
Y. Fu
R. Welsh
P. Jagasia
N. Dianati Maleki
A. Awad
C. Price
T. Temple
H Siha
Y. Zheng
Stroke Committee
G. Wilms
V. Thijs
F. Van de Werf, ACC 2013
CLINICAL OUTCOMES
After amendment (N=1503)
Before amendment (N=379)
F. Van de Werf, ACC 2013
CLINICAL OUTCOMES
Before amendment (N=379) After amendment (N=1503)