A Prospective, Randomized Comparison of Paclitaxel-eluting TAXUS Stents vs. Bare Metal Stents During...

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Transcript of A Prospective, Randomized Comparison of Paclitaxel-eluting TAXUS Stents vs. Bare Metal Stents During...

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A Prospective, Randomized Comparison of Paclitaxel-eluting TAXUS Stents vs. Bare Metal Stents During Primary Angioplasty in Acute Myocardial Infarction One Year Results Gregg W. Stone MD For the HORIZONS-AMI Investigators Slide 2 Background No consensus exists regarding the safety and efficacy of drug-eluting stents in pts with STEMI undergoing primary PCI No consensus exists regarding the safety and efficacy of drug-eluting stents in pts with STEMI undergoing primary PCI TLR and restenosis rates tend to be lower in STEMI vs. elective PCI patients because of less plaque burden and non viable myocardium The safety of implanting DES in ruptured plaques with thrombus has been questioned Outcomes from registry studies of DES vs. BMS in STEMI have been conflicting, and no large-scale randomized trials have been performed Outcomes from registry studies of DES vs. BMS in STEMI have been conflicting, and no large-scale randomized trials have been performed Slide 3 Harmonizing Outcomes with Revascularization and Stents in AMI 3602 pts with STEMI with symptom onset 12 hours Emergent angiography, followed by triage to Primary PCI CABG Medical Rx UFH + GP IIb/IIIa inhibitor (abciximab or eptifibatide) Bivalirudin monotherapy ( provisional GP IIb/IIIa) Aspirin, thienopyridine R 1:1 3000 pts eligible for stent randomization R 3:1 Bare metal EXPRESS stent Paclitaxel-eluting TAXUS stent Clinical FU at 30 days, 6 months, 1 year, and then yearly through 5 years; angio FU at 13 months Clinical FU at 30 days, 6 months, 1 year, and then yearly through 5 years; angio FU at 13 months Slide 4 Stent Randomization Hypotheses In patients with STEMI undergoing primary PCI, the use of paclitaxel-eluting TAXUS stents rather than bare metal EXPRESS stents will be: In patients with STEMI undergoing primary PCI, the use of paclitaxel-eluting TAXUS stents rather than bare metal EXPRESS stents will be: Efficacious, as evidenced by reduced rates of ischemia-driven target lesion revascularization at 1-year and angiographic binary restenosis at 13 months; and Safe, with non-inferior rates of the composite measure of death, reinfarction, stent thrombosis or stroke at 1-year Slide 5 Clinical Inclusion Criteria STEMI >20 mins and Angiographic Exclusion Criteria Bifurcation lesion definitely requiring implantation of stents in both the main vessel + side branch Bifurcation lesion definitely requiring implantation of stents in both the main vessel + side branch Infarct related artery is an unprotected left main Infarct related artery is an unprotected left main >100 mm of study stent length anticipated >100 mm of study stent length anticipated Infarction due to stent thrombosis, or infarct lesion at the site of a previously implanted stent Infarction due to stent thrombosis, or infarct lesion at the site of a previously implanted stent High likelihood of CABG within 30 days anticipated High likelihood of CABG within 30 days anticipated Slide 9 2 Primary Stent Endpoints (at 12 Months) 1) Ischemia-driven TLR* 2) Composite Safety MACE = All cause death, reinfarction, stent thrombosis (ARC definite or probable)**, or stroke and * Related to randomized stent lesions (whether study or non study stents were implanted); Major Secondary Endpoint (at 13 Months) Binary angiographic restenosis ** In randomized stent lesions with 1 stent implanted (whether study or non study stents) ** In randomized stent lesions with 1 stent implanted (whether study or non study stents) Slide 10 Statistical Methodology Second randomization stratification Second randomization stratification i.Results from the first randomization ii.Presence of medically treated diabetes mellitus iii.Presence of any lesion >26 mm in length (requiring overlapping stents by protocol) iv.U.S. vs. non-U.S. site Primary analysis conducted in the ITT cohort using Kaplan-Meier methodology, with the groups compared by log-rank Primary analysis conducted in the ITT cohort using Kaplan-Meier methodology, with the groups compared by log-rank 1-sided =0.025 for NI; 2-sided =0.05 for Sup 1-sided =0.025 for NI; 2-sided =0.05 for Sup Slide 11 Power Analysis Assumed event rates One Year TestEXPRESSTAXUSPower Ischemic TLR Superiority9.0%5.0%-95% Composite Safety MACE Noninferiority7.5%7.5%3.0%80% With 2,850 pts randomized 3:1* Assumed event rates 13 Months TestEXPRESSTAXUSPower RestenosisSuperiority26.0%15.6%-96% With angiographic FU in 1,125 randomized pts (analyzable) * Assumed 5% withdrew or lost to FU at 1 year 3000 randomized Slide 12 Study Organization Sponsor:The Cardiovascular Research Foundation Sponsor:The Cardiovascular Research Foundation Grant Support:Boston Scientific Corporation (unrestricted) The Medicines Company Grant Support:Boston Scientific Corporation (unrestricted) The Medicines Company Principal Investigator:Gregg W. Stone MD Principal Investigator:Gregg W. Stone MD Steering Committee:Gregg W. Stone (Chair), Bruce R. Brodie, David A. Cox, Cindy L. Grines, Barry D. Rutherford Steering Committee:Gregg W. Stone (Chair), Bruce R. Brodie, David A. Cox, Cindy L. Grines, Barry D. Rutherford European SteeringH Bonnier, A Colombo, Eulogio Garcia, Committee: E Grube, G Guagliumi, A Kastrati, P Serruys, H Suryapranata European SteeringH Bonnier, A Colombo, Eulogio Garcia, Committee: E Grube, G Guagliumi, A Kastrati, P Serruys, H Suryapranata Additional CountryY Almagor, A Banning, J Belardi, D Dudek, Leaders:L Grinfeld, K Huber, D Nilsen, G Olivecrona, L Rasmussen Additional CountryY Almagor, A Banning, J Belardi, D Dudek, Leaders:L Grinfeld, K Huber, D Nilsen, G Olivecrona, L Rasmussen PharmacologyDeepak Bhatt, George Dangas, Fred Feit, Committee:Magnus Ohman PharmacologyDeepak Bhatt, George Dangas, Fred Feit, Committee:Magnus Ohman Slide 13 Study Organization Data Management:CRF, Roxana Mehran (Director), Lynn Vandertie, Louise Gambone (Ops), Allison Kellock (Programming), Helen Parise (Stats) Data Management:CRF, Roxana Mehran (Director), Lynn Vandertie, Louise Gambone (Ops), Allison Kellock (Programming), Helen Parise (Stats) Clinical Events Committee:CRF, S. Chiu Wong (Chair) Clinical Events Committee:CRF, S. Chiu Wong (Chair) Site and Data Monitoring:J. Tyson and Associates (USA), Premier (Europe), Tango (S.A.) Site and Data Monitoring:J. Tyson and Associates (USA), Premier (Europe), Tango (S.A.) Angiographic Core Lab:CRF, Alexandra Lansky (Director), Ecaterina Cristea (Ops) Angiographic Core Lab:CRF, Alexandra Lansky (Director), Ecaterina Cristea (Ops) ECG Core Lab:CRF, James Reiffel (Director) ECG Core Lab:CRF, James Reiffel (Director) IVUS Core lab:CRF, Akiko Maehara (Director) IVUS Core lab:CRF, Akiko Maehara (Director) DSMB:Bernhard Gersh (Chair), David Faxon, Spencer King, Stuart Pocock, David Williams DSMB:Bernhard Gersh (Chair), David Faxon, Spencer King, Stuart Pocock, David Williams Slide 14 The Cardiovascular Research Foundation (CRF) HORIZONS-AMI Team Sponsored by CRF Slide 15 Horizons Enrollment - Centers USA (57) (1) Spain (6) UK (2) Norway (2) Norway Poland (9) Germany (16) Austria (5) (3) Netherlands Italy (2) Argentina (12) Israel (10) 3,602 pts randomized at 123 centers in 11 countries between March 25 th, 2005 and May 7 th, 2007 Slide 16 Top 20 Enrolling Sites 1. B. Witzenbichler, Germany 2. G. Guagliumi, Italy 3. J. Peruga, Poland 4. B. Brodie, USA 5. R. Kornowski, Israel 6. F. Hartmann, Germany 7. M. Moeckel, Germany 8. A. Ochala, Poland 9. W. Ruzyllo, Poland 10. V. Guetta, Israel 11. H. Suryapranata, Netherlands 12. K. Huber, Austria 13. J. Wehrle, Germany 14. C. Metzger, USA 15. M. Desaga, Germany 16. K. Zmudka, Poland 17. J. Kochman, Poland 18. D. Nilsen, Norway 19. D. Dudek, Poland 20. A. Finkelstein, Israel Slide 17 TAXUS DES N=2257 EXPRESS BMS N=749 Randomized 1 year FU N=2186 (96.9%) N=715 (95.5%) Withdrew Withdrew Lost to FU Lost to FU 1853727 R 3:1 Harmonizing Outcomes with Revascularization and Stents in AMI 3006 pts eligible for stent rand. Primary Medical Rx193 Primary CABG 62 Deferred PCI 2 Index PCI, not eligible - PTCA only119 - Stented220 UFH + GPI (n=1802) Bivalirudin (n=1800) R 1:1 3602 pts with STEMI 93.1% of all stented pts were randomized Slide 18 Baseline Characteristics (i) TAXUS(N=2257)EXPRESS(N=749) Age (years) 59.9 [52.4, 69.4] 59.3 [51.8, 69.2] Male77.0%76.0% Diabetes16.1%15.2% Hypertension51.2%51.9% Hyperlipidemia42.2%41.1% Current smoking 46.3%51.9% Prior MI 9.1%10.9% Prior PCI 9.5%7.7% Prior CABG 2.2%1.9% *P=0.009 * Slide 19 Baseline Characteristics (ii) TAXUS(N=2257)EXPRESS(N=749) Weight (kg) 80 [71, 90] Killip class 2-4 8.8%8.0% Anterior MI 42.2%44.7% LVEF (%), site 50 [44, 59] 50 [43, 58] Symptoms PCI, hrs 3.7 [2.7, 5.5] 3.8 [2.7, 5.8] Femoral a. access 93.6%92.9% Venous access 8.5%8.0% Closure device 30.1%28.8% Aspiration catheter 11.4%10.7% Slide 20 Study Drugs TAXUS(N=2257)EXPRESS(N=749) Aspirin at home 22.7%20.5% Aspirin load pre PCI 97.0%97.2% Thienopyridine at home 2.1%2.5% Thienopyridine loading dose 98.9%98.3% - clopidogrel 300 mg - clopidogrel 300 mg34.2%35.5% - clopidogrel 600 mg - clopidogrel 600 mg63.3%61.3% - clopidogrel other - clopidogrel other1.2%1.3% - ticlopidine - ticlopidine0.5%0.3% UFH pre randomization UFH pre randomization65.2%65.8% UFH as the procedural antithrombin UFH as the procedural antithrombin49.8%50.1% Bivalirudin administered Bivalirudin administered50.7%50.9% GP IIb/IIIa inhibitor administered 52.0%51.5% Slide 21 Procedural Data (Site Reported) TAXUS (N=2257, L=2495) EXPRESS (N=749, L=815) N lesions treated 1.1 0.4 - 2 lesions treated - 2 lesions treated11.1%9.0% - 2 vessels treated - 2 vessels treated4.5%3.1% Direct stenting attempted 30.4%33.7% Stent target lesion: LAD, LCX, RCA, LM, SVG 40.1%, 14.6%, 45.1%, 0.3%, 0.3% 42.4%, 15.9%, 41.3%, 0.4%, 0.4% N stents implanted 1.5 0.9 1.4 0.7 Total stent length** 30.8 17.8 27.3 14.9 Max balloon dia. (mm) 3.00 [2.75, 3.50] 3.00 [2.90, 3.50] Max pressure (atm.) 14.0 [12.0, 16.0] *P=0.002; **P Aspiri