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Gregg W. Stone, MD for the SPIRIT IV Investigators

SPIRIT IV A Prospective, Randomized Trial Comparing an Everolimus-Eluting Stent and a Paclitaxel-Eluting Stent in Patients with Coronary Artery Disease One Year Clinical Results. Gregg W. Stone, MD for the SPIRIT IV Investigators.

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Gregg W. Stone, MD for the SPIRIT IV Investigators

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  1. SPIRIT IVA Prospective, Randomized Trial Comparing an Everolimus-Eluting Stent and a Paclitaxel-Eluting Stent in Patients with Coronary Artery Disease One Year Clinical Results Gregg W. Stone, MDfor the SPIRIT IV Investigators

  2. Disclosures • Gregg W. Stone, MD • Advisory board for Abbott Vascular and Boston Scientific

  3. SPIRIT IV Background • The safety and efficacy of the XIENCE V EES have been demonstrated in the SPIRIT FIRST, SPIRIT II, and SPIRIT III randomized trials • However, these trials were not powered for superiority for clinical endpoints, nor to assess low frequency event rates (death, MI, stent thrombosis) • Routine angiographic follow-up may have affected the results • Whether the performance of EES is different from PES in pts with diabetes remains uncertain

  4. SPIRIT IV Study Algorithm RVD ≥2.5 mm - ≤3.75 mm; Lesion length ≤28 mm Max. 3 lesions with a maximum of 2 per epicardial vessel 3690 pts enrolled at 66 U.S. sites Pre-rand:ASA≥300 mg, clopidogrel ≥300 mg load unless on chronic Rx Randomized 2:1 XIENCE V®:TAXUS® Express2 Stratified by diabetes and presence of complex lesions Pre-dilatation mandatory Paclitaxel-eluting TAXUS Everolimus-eluting XIENCE V Aspirin ≥80 mg QD for 5 years; clopidogrel 75mg QD for at least 12 mos (if not at high risk for bleeding) Clinical f/u only: 1, 6, 9 months and yearly for 1-5 years

  5. Major Exclusion Criteria • Any target lesion or vessel meets any of the following: • Left main or ostial LAD/LCX • In or distal to a bypass graft conduit • Bifurcation with sidebranch diameter ≥2 mm AND ostial DS >50% OR requiring pre-dilatation • Total occlusion, thrombus, restenotic, excessive tortuosity, angulation or heavy calcification • Prior coronary brachytherapy • High probability of additional PCI within 9 mos

  6. SPIRIT III / SPIRIT IV Differences

  7. SPIRIT IV Endpoints • Primary endpoint: • Target lesion failure (TLF) at 1 year • Major secondary endpoints: • Ischemia-driven TLR at 1 year • Composite endpoint of cardiac death or target vessel MI at 1 year • All 3 endpoints powered for sequential noninferiority and superiority testing TLF = cardiac death, target vessel MI, or ischemia-driven TLR

  8. SPIRIT IV Trial Organization • Principal Investigator: Gregg W. Stone,MD Columbia University Medical Center, NY • Angiographic Core Lab: Alexandra Lansky, MD CRF, NY, NY • CEC: Don Cutlip, MD Harvard Clinical Research Institute, MA • DSMB: Robert N. Piana, MD (chair) Vanderbilt, Nashville, TN • Randomization Service: ICON Clinical Research Sugarland, TX • Electronic Data Capture: Phase Forward Waltham, MA • Data management Abbott Vascular and sponsor: Santa Clara, CA

  9. SPIRIT IV Top 20 Enrollers

  10. SPIRIT IV Patient Flow Enrolled (N=3690) 3 = Randomization errors Randomized (N=3687) TAXUS(N=1229) XIENCE V (N=2458) Lost to f/u = 35 Withdrawal = 7 Other = 0 24 = Lost to f/u 8 = Withdrawal 2 = Other 1-Year Follow-up*(N=3611; 97.9%) TAXUS(N=1195) XIENCE V (N=2416) *F/U window: ± 28 days

  11. Baseline Demographics

  12. Baseline Angiography

  13. Procedural Results

  14. Antiplatelet Agent Utilization

  15. Primary Endpoint: TLF Through 1 Year Diff [95%CI] = -2.6% [-4.2%, -1.0%] RR [95%CI] = 0.62 [0.46, 0.82] pNI<0.0001 pSup=0.001 Target lesion failure (%) 101/2416 81/1195 XIENCE V TAXUS TLF = cardiac death, target vessel MI, or ischemia-driven TLR 1 Year = 365 ± 28 days

  16. TLF Through 1 Year HR [95%CI] = 0.61 [0.46, 0.82] XIENCE V TAXUS p=0.0008 6.6% Δ 2.7% Target lesion failure (%) 3.9% Months TLF = cardiac death, target vessel MI, or ischemia-driven TLR

  17. TVF, TLF, and MACE Through 1 Year RR [95%CI] = 0.71 [0.55, 0.92] p=0.009 XIENCE V TAXUS RR [95%CI] = 0.62 [0.46, 0.82] p=0.0009 RR [95%CI] = 0.62 [0.46, 0.82] p=0.001 % 101/2416 81/1195 135/2416 94/1195 82/1195 102/2416 MACE TVF TLF TLF = cardiac death, target vessel MI, or ID-TLR; MACE = cardiac death, all MI, or ID-TLR; TVF = cardiac death, all MI, or ID-TVR. 1 Year = 365 ± 28 days

  18. Major 2° Endpoint: ID-TLR Through 1 Year Diff [95%CI] = -2.1% [-3.4%, -0.7%] RR [95%CI] = 0.55 [0.38, 0.78] pNI<0.0001 pSup=0.001 Ischemia-driven TLR (%) 61/2416 55/1195 XIENCE V TAXUS 1 Year = 365 ± 28 days

  19. Ischemia-Driven TLR Through 1 Year HR [95%CI] = 0.54 [0.38, 0.78] XIENCE V TAXUS p=0.0008 4.5% Δ 2.2% Ischemia-driven TLR (%) 2.3% Months

  20. Major 2° EP: Cardiac Death or TV MI Through 1 Yr Diff [95%CI] = -1.0% [-2.1%, 0.2%] RR [95%CI] = 0.69 [0.46, 1.04] pNI<0.0001 pSup=0.09 Cardiac death or MI (%) 53/2416 38/1195 XIENCE V TAXUS TV MI = target vessel MI 1 Year = 365 ± 28 days

  21. Cardiac Death or TV MI Through 1 Year HR [95%CI] = 0.69 [0.46, 1.05] XIENCE V TAXUS p=0.08 3.1% Δ 0.9% Cardiac death or MI (%) 2.2% Months MI = Target Vessel MI

  22. TLF Components Through 1 Year RR [95%CI] = 0.55 [0.38, 0.78] p=0.001 XIENCE V TAXUS RR [95%CI] = 0.62 [0.40, 0.96] p=0.04 % RR [95%CI] = 0.99 [0.34, 2.89] p=1.00 44/2416 35/1195 10/2416 5/1195 55/1195 61/2416 ID-TLR Cardiac Death Target Vessel MI TLF = cardiac death, target vessel MI, or ischemia-driven TLR 1 Year = 365 ± 28 days

  23. Death and MI at 1 Year MI = Target Vessel MI + Non-Target Vessel MI Categorical data, 365 ± 28 days

  24. Stent Thrombosis (Protocol Definition)* XIENCE V HR [95%CI] = 0.20 [0.06, 0.63] TAXUS p=0.002 Stent thrombosis (%) 0.82% Δ 0.66% 0.16% Months *ACS + angiographic thrombus, or unexplained death or STEMI/Q-wave MI in TL distribution within 30 days

  25. Stent Thrombosis (Protocol Definition)* Acute (0 – 24 hours) Subacute (>24 hours – 30 days) Late (>30 days – 1 year)** XIENCE V N=2458 0.17 % p=0.004 TAXUS N=1229 0.85% Stent thrombosis (%) *ACS + angiographic thrombus, or unexplained death or STEMI/Q-wave MI in TL distribution within 30 days **Categorical data, 365 ± 28 days

  26. Stent Thrombosis (ARC Def or Prob) HR [95%CI] = 0.27 [0.11, 0.67] XIENCE V TAXUS p=0.003 1.06% Stent thrombosis (%) Δ 0.77% 0.29% Months

  27. Stent Thrombosis (ARC Definition)* Acute (0 – 24 hours) Subacute (>24 hours – 30 days) Late (>30 days – 1 year)** XIENCE V N=2458 0.29% p=0.004 TAXUS N=1229 1.10% Stent thrombosis (%) *Definite or Probable per ARC definition **Categorical data, 365 ± 28 days

  28. SPIRIT IV: 11 Subgroups Examined Age < 65 (n=1993) Lesion number = 1 (n=2710) Age ≥ 65 (n=1618) Lesion number = 2 or 3 (n=901) - Lesion number = 2 (n=784) Male (n=2450) - Lesion number = 3 (n=117) Female (n=1161) Lesion length ≤ median (13.3 mm; n=1349) Hypertension* (n=2778) Lesion length > median (13.3 mm; n=1346) No hypertension* (n=828) Hypercholesterolemia* (n=2701) Bailout stent required (n=221) No hypercholesterolemia* (n=852) No bailout stent required (n=3390) BMI ≥ 30 (n=1758) No diabetes (n=2467) BMI < 30 (n=1853) Diabetes (n=1140) Stable angina (n=2085) - Diabetics not requiring insulin (n=826) No stable angina (n=1458) - Diabetics requiring insulin (n=314) RVD ≤ median (2.75 mm; n=1352) RVD > median (2.75 mm; n=1351) RVD and lesion length from single lesion treated subgroup. * Requiring medication RVD range (min, max; mm): X = (1.39, 4.71), T = (1.36, 4.70) Lesion length range (min, max; mm): X = (1.99, 54.80), T = (1.72, 47.10)

  29. SPIRIT IV Subgroup Analysis: TLF at 1 Year EES better PES better TLF = cardiac death, target vessel MI, or ischemia-driven TLR; 1 Year = 365 ± 28 days. *Requiring medication

  30. SPIRIT IV Subgroup Analysis: TLF at 1 Year EES better PES better TLF = cardiac death, target vessel MI, or ischemia-driven TLR; 1 Year = 365 ± 28 days Single lesion treated data are used for RVD & lesion length subgroup analyses

  31. Impact of Diabetes on TLF XIENCE V TAXUS RR [95%CI] = 0.47 [0.32, 0.68] p<0.0001 RR [95%CI] = 0.94 [0.59, 1.49] p=0.80 TLF (%) 52/1652 55/815 49/761 26/379 TLF = cardiac death, target vessel MI, or ischemia-driven TLR Pinteraction = 0.02

  32. Clinical Outcomes Through 1 Year - No Diabetes Mellitus - TLF = cardiac death, target vessel MI, or ID-TLR; MACE = cardiac death, all MI, or ID-TLR; TVF = cardiac death, all MI, or ID-TVR. 1 Year = 365 ± 28 days

  33. Clinical Outcomes Through 1 Year - Diabetes Mellitus - TLF = cardiac death, target vessel MI, or ID-TLR; MACE = cardiac death, all MI, or ID-TLR; TVF = cardiac death, all MI, or ID-TVR. 1 Year = 365 ± 28 days

  34. Impact of Diabetes Type on TLF XIENCE V TAXUS RR [95%CI] = 1.16 [0.51, 2.62] p=0.83 RR [95%CI] = 0.86 [0.49, 1.50] p=0.64 TLF (%) 33/562 18/264 16/199 8/115 Diabetes not requiring insulin Diabetes requiring insulin TLF = cardiac death, target vessel MI, or ischemia-driven TLR Pinteraction = 0.56

  35. SPIRIT IV Conclusions In the large-scale, prospective multicenter randomized SPIRIT IV trial, the everolimus-eluting XIENCE V stent compared to the paclitaxel-eluting TAXUS Express stent at 1-year follow-up demonstrated: • Primary endpoint: Significantly reduced rate of TLF • Major secondary endpoints: Significantly reduced rate of TLR and noninferior rate of cardiac death or target vessel MI • Other secondary endpoints: Significantly reduced rates of stent thrombosis (protocol and ARC), target vessel MI and all MI, with comparable rates of cardiac death and all-cause death • Diabetic subgroup: Comparable rate of TLF in pts with diabetes, and a marked reduction in TLF in pts without diabetes • Other subgroups: Consistent relative reductions in TLF independent of clinical features, vessel size, and # and length of treated lesions

  36. Clinical Implications • The results with the XIENCE V stent demonstrating enhanced safety and efficacy compared to TAXUS EXPRESS in this large-scale study without routine angiographic follow-up and with 100% monitoring set a new standard for event-free survival after DES • The simultaneous reduction of stent thrombosis, MI and TLR with XIENCE V demonstrates that “low late loss” may be achieved with DES without sacrificing safety • Outcomes in pts with diabetes may still be improved, and should represent an area of focus for future development of novel drugs and enhanced stent design

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