PHARMACO-INVASIVE STRATEGY COMPARED WITH PPCI: DESIGN AND MAIN OUTCOMES OF THE STREAM TRIAL

Transcription

1 PHARMACO-INVASIVE STRATEGY COMPARED WITH PPCI: DESIGN AND MAIN OUTCOMES OF THE STREAM TRIAL Frans Van de Werf Leuven, Belgium

2 Disclosures 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

3 Background 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

4 Study aim 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.

5 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

6 PCI Hospital Ambulance/ER Study protocol STEMI <3 hrs from onset symptoms, PPCI <60 min not possible, 2 mm ST-elevation in 2 leads RANDOMIZATION 1:1 by IVRS, OPEN LABEL Strategy A: pharmaco-invasive Strategy B: primary PCI <75y: full dose 75y: ½ dose TNK* no lytic Aspirin Clopidogrel: LD 300 mg + 75 mg QD Enoxaparin: 30 mg IV + 1 mg/kg SC Q12h Aspirin Clopidogrel: 75 mg QD Enoxaparin: 0.75 mg/kg SC Q12h Antiplatelet and antithrombin treatment according to local standards ECG at 90 min: ST resolution 50% YES NO Angio >6 to 24 hrs PCI/CABG if indicated Immediate angio + rescue PCI if indicated Standard primary PCI Primary endpoint: composite of all cause death or shock or CHF or reinfarction up to day 30 *half dose TNK is not covered by the label

7 PCI Hospital Ambulance/ER Study protocol STEMI <3 hrs from onset symptoms, PPCI <60 min not possible, 2 mm ST-elevation in 2 leads RANDOMIZATION 1:1 by IVRS, OPEN LABEL Strategy A: pharmaco-invasive Strategy B: primary PCI <75y: full dose Aspirin Clopidogrel: LD 300 mg + 75 mg QD Enoxaparin: 30 mg IV + 1 mg/kg SC Q12h After 75y: 20% ½ of dose the TNK* planned recruitment, the TNK dose was reduced by 50% among patients 75 years of age.* Aspirin Clopidogrel: 75 mg QD Enoxaparin: 0.75 mg/kg SC Q12h no lytic Antiplatelet and antithrombin treatment according to local standards ECG at 90 min: ST resolution 50% YES NO Angio >6 to 24 hrs PCI/CABG if indicated Immediate angio + rescue PCI if indicated Standard primary PCI Primary endpoint: composite of all cause death or shock or CHF or reinfarction up to day 30 *half dose TNK is not covered by the label

8 Enrolment and key dates 1892 patients randomised by 99 sites in 15 countries First patient in: March 19, 2008 Last patient in: July 26, 2012 Last patient out: Sept 7, 2012 Enrolment setting 81% 19% EMS Community hospital

9 Patients per country

10 Baseline characteristics (1) Pharmaco-invasive (N=944) PPCI (N=948) Age (yrs) 59.7 (12.4) 59.6 (12.5) Age 75 y (%) 14% 13% Women (%) 21% 22% Weight (kg) 80.5 (14.8) 80.0 (14.9) Killip class (%) I II/III IV 94% 6% <1% 94% 5% <1% Heart rate (bpm) 74.9 (18.4) 75.5 (18.1) Systolic BP (mmhg) (22.7) (23.3) Infarct location Data are mean (SD) or % Anterior Inferior Other 48% 50% 2% 46% 53% 2%

11 Baseline characteristics (2) Pharmaco-invasive (N=944) PPCI (N=948) Previous MI 9% 10% Previous PCI 6.4% 8.8% Previous CABG <1% <1% Previous congestive heart failure <1% 2% Hypertension 47% 44% Diabetes 12% 13% Data are %

12 Median times to treatment (min) Sx onset 1 st Medical contact Randomise IVRS Rx TNK min Sx onset 1 st Medical contact Randomise IVRS 78 min difference Rx PPCI = Hour 2 Hours 178 min

13 Median times to treatment (min) Sx onset 62 1 st Medical contact Randomise IVRS 29 9 Rx TNK 100 min 36% Rescue PCI at 2.2h 64% non-urgent cath at 17h Sx onset 1 st Medical contact Randomise IVRS Rx PPCI = Hour 2 Hours 178 min

14 PATIENTS TIMI flow rates 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% P<0.001 P= Pharmaco-invasive (N=944) PPCI (N=948) TIMI before PCI TIMI after PCI

15 Invasive procedures Pharmaco-invasive (N=944) PPCI (N=948) P-value PCI performed 80% 90% <0.001 Stents deployed 96% 96% 0.95 CABG performed 4.7% 2.1% 0.002

16 Dth/Shock/CHF/ReMI (%) Primary endpoint TNK vs PPCI Relative Risk 0.86, 95%CI ( ) PPCI 14.3% TNK 12.4% p=0.24 (n.s.*) Days since randomisation *n.s. = non-significant

17 Dth/Shock/CHF/ReMI (%) Primary endpoint TNK vs PPCI Relative Risk 0.86, 95%CI ( ) PPCI 14.3% TNK 12.4% p=0.24 The 95% CI of the observed incidence in the pharmaco-invasive arm would exclude a 9% relative excess compared with PPCI (n.s.*) Days since randomisation *n.s. = non-significant

18 Single endpoints up to 30 days All cause death Cardiac death Pharmaco-invasive (N=944) (43/939) 4.6% (31/939) 3.3% PPCI (N=948) (42/946) 4.4% (32/946) 3.4% P-value 0.88 (n.s.*) 0.92 (n.s.*) Congestive heart failure (57/939) 6.1% (72/943) 7.6% 0.18 (n.s.*) Cardiogenic shock (41/939) 4.4% (56/944) 5.9% 0.13 (n.s.*) Reinfarction (23/938) 2.5% (21/944) 2.2% 0.74 (n.s.*) *n.s. = non-significant

19 Subgroup analyses for primary endpoint within 30 days p=0.07

20 Stroke rates TOTAL POPULATION (N=1892) Pharmaco-invasive PPCI P-value Total stroke 15/939 (1.60%) 5/946 (0.53%) 0.03 fatal stroke 7/939 (0.75%) 4/946 (0.42%) 0.39 Haemorrhagic stroke 9/939 (0.96%) 2/946 (0.21%) 0.04 fatal haemorrhagic stroke 6/939 (0.64%) 2/946 (0.21%) 0.18 POST AMENDMENT POPULATION (N=1503) Total stroke 9/747 (1.20%) 5/756 (0.66%) 0.30 fatal stroke 3/747 (0.40%) 4/756 (0.53%) >0.999 Haemorrhagic stroke 4/747 (0.54%) 2/756 (0.26%) 0.45 fatal haemorrhagic stroke 2/747 (0.27%) 2/756 (0.26%) >0.999

21 In-hospital bleeding complications Pharmaco-invasive (N=944) PPCI (N=948) P-value Major non-ich bleeding 6.5% 4.8% 0.11 (n.s.*) Minor non-ich bleeding 21.8% 20.2% 0.40 (n.s.*) Blood transfusions 2.9% 2.3% 0.47 (n.s.*) *n.s. = non-significant

22 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.

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24 Acknowledgements Executive Committee F Van de Werf P. Armstrong A. Gershlick P. Goldstein R. Wilcox Boehringer- Ingelheim T. Danays E. Bluhmki A. Regelin G. Goetz 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. Kendall T. Quinn J Adgey 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 DSMB K. Fox G. Montalescot C. Pollack J. Tijssen W. Weaver R. Brower Statistical Analysis Committee E. Lesaffre K. Bogaerts A. Belmans G. Kalema E. Bluhmki 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