1 / 18

COI Disclosure for Dr. Montalescot are availalble @ http :// action-coeur

ACCOAST. A C omparison of p rasugrel at the time of percutaneous C oronary intervention O r as pretreatment A t the time of diagnosis in patients with non- ST -elevation MI. G Montalescot, L Bolognese, D Dudek, P Goldstein, C Hamm, JF Tanguay,

ganesa
Download Presentation

COI Disclosure for Dr. Montalescot are availalble @ http :// action-coeur

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. ACCOAST AComparison of prasugrelat the time of percutaneousCoronary intervention Or as pretreatment At the time of diagnosis in patients with non-ST-elevationMI G Montalescot, L Bolognese, D Dudek, P Goldstein, C Hamm, JF Tanguay, JM ten Berg, DL Miller, TM Costigan, J Goedicke, J Silvain, P Angioli, J Legutko, M Niethammer, Z Motovska, JA Jakubowski, G Cayla, LO Visconti, E Vicaut, P Widimskyfor the ACCOAST investigators COI Disclosure for Dr. Montalescotareavailalble @http://www.action-coeur.org

  2. Trial conduct • Coordinating Center: ACTION Study Group - Institute of Cardiology – Pitié-Salpêtrière UniversityHospital, Paris, France • Sponsors: Daiichi-Sankyo Company, Ltd. and Eli Lilly and Company • Global Trial Operations: ICON Clinical Research and Quintiles (site management), Inventiv (data management and statistical services), Tata Consultancy Services (statistical programming) • External Academic Statistical Center : ACTION Study Group • Executive Committee: G Montalescot (Chairman), L Bolognese, D Dudek, P Goldstein, C Hamm, JF Tanguay, J ten Berg, P Widimsky • Endpoint Adjudication Committee: M Flather(Chairman), A Bardají, A Baumbach, M Dalby, A Kapur, F Philippe, P Sabouret, AF van den Heuvel,A Zaman • Data Safety Monitoring Board:M Bertrand (Chairman), CDi Mario, E Vicaut

  3. Enrollment:>4,000patients in 19 Countries Poland: 847 Finland: 42 Sweden: 4 Latvia: 5 Lithuania: 73 Slovakia: 47 Canada: 146 Hungary: 134 Netherlands: 142 Romania: 85 Belgium: 81 Turkey: 112 Portugal: 17 Israel: 131 Germany: 529 France: 586 Czech Rep: 292 Austria: 172 Italy: 628

  4. Early Enrollment Completion • The DSMB after the last scheduled meeting (Nov 2012) recommended to stop enrollment, pretreatmentbeing associatedwith an increased risk of major bleedingwith no reduction in CV events (but no between-group imbalance in mortality) • Investigators and Regulatory agencies were immediately notified the enrollment to the ACCOAST study was stopped. • Follow-up of patients continued. The PI and ACCOAST study team remained blinded until the datalock. • Sample size calculation: 400 patients with a 1° EP event (approximately 4100 patients needed) • End of study: 398 patients had an event (4033 patients enrolled)

  5. P2Y12 Pre-treatment ESC Recommendations

  6. Pre-treatment with aspirin and a P2Y12 antagonist has been a class I recommendation and common practice for the treatment of NSTE-ACS • However, no trial has ever randomized patients presenting with NSTE-ACS, invasively managed, to pre-treatment with clopidogrel, prasugrel or ticagrelor vs. no pre-treatment.

  7. NSTEMI + Troponin ≥ 1.5 times ULN local lab value Clopidogrel naive or on long term clopidogrel 75 mg n~4100 (event driven) ACCOAST design Randomize 1:1 Double-blind Prasugrel 30 mg Placebo CABG or Medical Management (no more prasugrel) CABG or Medical Management (no prasugrel) Coronary Angiography Coronary Angiography Prasugrel 60 mg Prasugrel 30 mg PCI PCI Prasugrel 10 mg or 5 mg (based on weight and age) for 30 days 1° Endpoint: CV Death, MI, Stroke, UrgRevasc, GP IIb/IIIabailout, at 7 days Montalescot G et al. Am Heart J 2011;161:650-656

  8. Main Inclusion/Exclusion Criteria Inclusion • NSTEMI symptoms within 48 hours prior to study entry • Elevated troponin (≥1.5 times ULN) per local lab(s) • Patient to be scheduled for coronary angiography and PCI within 2 hours to 24 hours of randomization and no later than 48 hours after randomization Exclusion • STEMI patients • Medical history contraindicating therapy with prasugrel • History of stroke or transient ischemic attack (TIA) • LD of any P2Y12 antagonist ≤7 days of study entry Montalescot G et al. Am Heart J 2011;161:650-656

  9. Total Randomized N=4038 Patient Disposition 5 Subjects Revoked Consent ITT and All Treated N= 4033 No Pre-treatment N=1996 Pre-treatment N=2037 Day 7 N=1964 (98.4%) Day 7 N=2009 (98.6%) Day 30 Visit N=1958 (96.1%) Day 30 Visit N=1924 (96.4%) Lost to Follow-up 2 (0.10) Lost to Follow-up 1 (0.05)

  10. Baseline Characteristics

  11. Baseline Characteristics

  12. 1° Efficacy End Point @ 7 + 30 days (All Patients) 15 CV Death, MI, Stroke, UR, GPIIb/IIIa Bailout Pre-treatment Pre-treatment 10.8 10.0 10 No Pre-treatment 10.8 No Pre-treatment Endpoint (%) 9.8 Hazard Ratio, 0.997 (95% 0.83, 1.20) 5 P=0.98 Hazard Ratio, 1.02 (95% 0.84, 1.25) P=0.81 0 0 5 10 15 20 25 30 Days From First Dose No. at Risk, Primary Efficacy End Point: 1996 1769 1762 No pre-treatment 1788 1775 1752 1621 2037 1802 1797 Pre-treatment 1821 1809 1791 1616

  13. 1° Efficacy Endpoint Through 7 Days for Prespecified Subgroups (All Patients) *Hazard ratio not evaluated for <10 events. †Interaction p-value is from a Cox proportional hazards model with treatment, subgroup, and the treatment-by-subgroup interaction as fixed effects; PCI includes 11 patients with PCI + CABG.

  14. All TIMI (CABG or non-CABG) Major Bleeding (All Treated patients) 5 Hazard Ratio, 1.90 Hazard Ratio, 1.97 (95% 1.19, 3.02) (95% 1.26, 3.08) 4 P=0.006 P=0.002 Pre-treatment 2.9 3 Pre-treatment 2.6 Endpoint (%) 2 All TIMI Major Bleeding 1 No Pre-treatment 1.5 0 No Pre-treatment 1.4 0 5 10 15 20 25 30 Days From First Dose No. at Risk, All TIMI Major Bleeding: No pre-treatment 1947 1328 1284 1263 1996 1297 1288 Pre-treatment 1972 1339 1297 1280 2037 1310 1299

  15. All TIMI Major Bleeding for Prespecified Subgroups Through 7 days (All Treated Patients) *Hazard ratio not evaluated for <10 events. †Interaction p-value is from a Cox proportional hazards model with treatment, subgroup, and the treatment-by-subgroup interaction as fixed effects; ‡CRUSADE score is a post-hoc analysis; PCI includes 11 patients with PCI + CABG.

  16. Conclusions • In NSTE-ACS patientsmanagedinvasivelywithin 48 hoursofadmission, pre-treatment withprasugreldoesnot reducemajorischemiceventsthrough 30 days but increasesmajorbleedingcomplications. • The resultsareconsistentamongpatientsundergoing PCI supportingtreatmentwithprasugreloncethecoronaryanatomyhasbeendefined. • Nosubgroupappearstohave a favorable risk/benefitratioofpre-treatment. • Reappraisalofroutinepre-treatment strategies in NSTE-ACS isneeded.

  17. Thank you to all investigators in 19 countries, at 171 Centers

More Related