stream strategic reperfusion early after myocardial infarction

F. Van de Werf, ACC 2013

STREAMSTRATEGIC REPERFUSION EARLY AFTER

MYOCARDIAL INFARCTION


• 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


• 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


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


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


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.


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


PATIENTS PER COUNTRY


BASELINE CHARACTERISTICS (1)

Data are mean (SD) or %


BASELINE CHARACTERISTICS (2)

Data are %


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


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


TIMI FLOW RATES

TIMI before PCI TIMI after PCI

P<0.001 P=0.41


INVASIVE PROCEDURES


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


SINGLE ENDPOINTS UP TO 30 DAYS


>

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


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


STROKE RATES


IN-HOSPITAL BLEEDING COMPLICATIONS


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.


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


CLINICAL OUTCOMES

After amendment (N=1503)

Before amendment (N=379)


CLINICAL OUTCOMES

Before amendment (N=379) After amendment (N=1503)

stream strategic reperfusion early after myocardial infarction

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