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SPIRIT IV A Prospective, Randomized Trial Comparing an Everolimus-Eluting Stent and a Paclitaxel-Eluting Stent in Patients with Coronary Artery Disease.

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Presentation on theme: "SPIRIT IV A Prospective, Randomized Trial Comparing an Everolimus-Eluting Stent and a Paclitaxel-Eluting Stent in Patients with Coronary Artery Disease."— Presentation transcript:

1 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

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

3 The safety and efficacy of the XIENCE V EES have been demonstrated in the SPIRIT FIRST, SPIRIT II, and SPIRIT III randomized trials 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) 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 Routine angiographic follow-up may have affected the results Whether the performance of EES is different from PES in pts with diabetes remains uncertain Whether the performance of EES is different from PES in pts with diabetes remains uncertain SPIRIT IV Background

4 Everolimus-eluting XIENCE V Paclitaxel-eluting TAXUS 3690 pts enrolled at 66 U.S. sites RVD 2.5 mm mm; Lesion length 28 mm Max. 3 lesions with a maximum of 2 per epicardial vessel Pre-rand: ASA 300 mg, clopidogrel300 mg load unless on chronic Rx Randomized 2:1 XIENCE V ® :TAXUS ® Express 2 Stratified by diabetes and presence of complex lesions Pre-dilatation mandatory Clinical f/u only: 1, 6, 9 months and yearly for 1-5 years Aspirin 80 mg QD for 5 years; clopidogrel 75mg QD for at least 12 mos (if not at high risk for bleeding) SPIRIT IV Study Algorithm

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 IIISPIRIT IV N patients Max. N lesions per pt23 Max. N vessels per pt23 Max. N lesions per vessel12 Bifurcation lesions <50% ostial DS and <2.0 mm <50% ostial DS or <2.0 mm Ostial RCA lesionsNoYes N pts with diabetes mellitus290/999 (29.0%)1185/3683 (32.2%) N pts with intended angio F/U564 (56.3%)0 SPIRIT III / SPIRIT IV Differences

7 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 SPIRIT IV Endpoints

8 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 managementAbbott Vascular and sponsor:Santa Clara, CA SPIRIT IV Trial Organization

9 Patients A. Rizvi The Heart Center of IN, Indianapolis, IN 292 J. Williams Presbyterian Hospital, Charlotte, NC 112 W. Newman Wake Medical Center, Raleigh, NC 263 M. Collins Columbia Univ. Med. Ctr., New York, NY 86 K. Mastali St. Joseph Medical Center, Towson, MD 196 P. Gordon The Miriam Hospital, Providence, RI 82 J. Wang Union Memorial Hospital, Baltimore, MD 155 M. Turco WA Adventist Hosp., Takoma Park, MD 81 D. Kereiakes The Christ Hospital, Cincinnati, OH 153 S. Hearne Peninsula Reg. Med. Ctr., Salisbury, MD 78 R. Caputo St. Josephs Hospital, Syracuse, NY 153 H. Dauerman Fletcher Allen Healthcare, Burlington, VT 71 N. Farhat EMH Regional Medical Center, Elyria, OH 138 F. Fleischhauer Sacred Heart Hospital, Pensacola, FL 70 R. Applegate N. Carolina Baptist Hosp., NC 124 C. Hirsch The Valley Hospital, Ridgewood, NJ 62 L. Cannon Northern Michigan Hospital, Petoskey, MI 123 K. Skelding Geisinger Medical Center, Danville, PA 57 J. Maddux St. Patrick Hospital, Missoula, MT 114 T. Fischell Borgess MedicalCenter, Kalamazoo, MI 57 SPIRIT IV Top 20 Enrollers

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

11 XIENCE V 2458 pts TAXUS 1229 pts P value Age (in years)63.3 ± ± Male (%) Hypertension (%) Hypercholesterolemia (%) Diabetes mellitus (%) Insulin requiring (%) Current smoker (%) Prior MI (%) Unstable angina (%) Baseline Demographics

12 XIENCE V 3142 lesions TAXUS 1585 lesions P value Lesion location LAD40.5%39.8%0.68 LCX24.2%25.4%0.35 RCA35.4%34.8%0.68 LMCA0.0% - QCA RVD (mm)2.75 ± ± MLD (mm)0.75 ± ± % DS72.3 ± ± Lsn length (mm)14.8 ± ± Baseline Angiography

13 XIENCE V 2458 pts 3142 lsns TAXUS 1229 pts 1585 lsns P value # lesions/patient1.3 ± lesion75.2%74.7% lesion21.7%21.6% lesion3.1%3.7%0.33 # stents/patient1.5 ± # stents/lesion1.17 ± ± Max. stent diameter/lesion (mm)3.01 ± ± Max. stent diameter/RVD/lesion1.11 ± ± Total stent length/lesion (mm)22.4 ± ± 8.9< Total stent length/lesion length1.65 ± ± 0.71< Procedural Results

14 XIENCE V 2458 pts TAXUS 1229 pts P value Aspirin - At 180 days98.8%98.5% At 270 days98.1%98.0% At 365 days97.1% 1.00 Thienopyridine - At 180 days98.8%99.2% At 270 days97.8%98.0% At 365 days94.9%95.1%0.87 Antiplatelet Agent Utilization

15 Target lesion failure (%) 101/241681/1195 XIENCE VTAXUS Primary Endpoint: TLF Through 1 Year TLF = cardiac death, target vessel MI, or ischemia-driven TLR 1 Year = 365 ± 28 days Diff [95%CI] = -2.6% [-4.2%, -1.0%] RR [95%CI] = 0.62 [0.46, 0.82] p NI < p Sup =0.001

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

17 TVF RR [95%CI] = 0.71 [0.55, 0.92] p=0.009 RR [95%CI] = 0.62 [0.46, 0.82] p=0.001 RR [95%CI] = 0.62 [0.46, 0.82] p= / / / / / /2416 TLF MACE % TVF, TLF, and MACE Through 1 Year 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 XIENCE VTAXUS

18 Ischemia-driven TLR (%) 61/241655/1195 XIENCE V TAXUS Major 2° Endpoint: ID-TLR Through 1 Year 1 Year = 365 ± 28 days Diff [95%CI] = -2.1% [-3.4%, -0.7%] RR [95%CI] = 0.55 [0.38, 0.78] p NI < p Sup =0.001

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

20 Cardiac death or MI (%) 53/241638/1195 XIENCE VTAXUS Major 2° EP: Cardiac Death or TV MI Through 1 Yr TV MI = target vessel MI 1 Year = 365 ± 28 days Diff [95%CI] = -1.0% [-2.1%, 0.2%] RR [95%CI] = 0.69 [0.46, 1.04] p NI < p Sup =0.09

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

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

23 XIENCE V 2458 pts TAXUS 1195 pts P value Death, all1.0%1.3% Cardiac0.4% Non cardiac0.6%0.8%0.52 MI, all1.9%3.1% Q-wave0.1%0.4% Non Q-wave1.7%2.8%0.05 All death or MI2.8%4.1%0.05 Cardiac death or MI2.2%3.3%0.07 MI = Target Vessel MI + Non-Target Vessel MI Categorical data, 365 ± 28 days Death and MI at 1 Year

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

25 XIENCE V N=2458 TAXUS N=1229 Stent thrombosis (%) 0.17 % 0.85% p=0.004 Stent Thrombosis (Protocol Definition)* Acute (0 – 24 hours)Subacute (>24 hours – 30 days)Late (>30 days – 1 year)** *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) Number at risk XIENCE V TAXUS % 0.29% Months p=0.003 HR [95%CI] = 0.27 [0.11, 0.67] Δ 0.77% Stent thrombosis (%) XIENCE V TAXUS

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

28 SPIRIT IV: 11 Subgroups Examined - Diabetics not requiring insulin (n=826) - Diabetics requiring insulin (n=314) Diabetes (n=1140) No diabetes (n=2467) - Lesion number = 2 (n=784) - Lesion number = 3 (n=117) Lesion number = 1 (n=2710) Lesion number = 2 or 3 (n=901) RVD median (2.75 mm; n=1352) RVD > median (2.75 mm; n=1351) Lesion length median (13.3 mm; n=1349) Lesion length > median (13.3 mm; n=1346) Age < 65 (n=1993) Age 65 (n=1618) 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) Bailout stent required (n=221) No bailout stent required (n=3390) Hypertension* (n=2778) No hypertension* (n=828) Hypercholesterolemia* (n=2701) No hypercholesterolemia* (n=852) BMI 30 (n=1758) BMI < 30 (n=1853) Stable angina (n=2085) No stable angina (n=1458) Male (n=2450) Female (n=1161)

29 Group EES (%) PES (%) Relative Risk (95% CI) Relative Risk (95% CI) P interaction All randomized (n=3687) [0.46, 0.82] Age 65 yrs (n=1618) [0.43, 1.09] 0.53 Age < 65 yrs (n=1993) [0.40, 0.82] Male (n=2450) [0.47, 0.95] 0.43 Female (n=1161) [0.33, 0.85] Hypertension* (n=2778) [0.41, 0.78] 0.30 No hypertension* (n=828) [0.44, 1.55] Hypercholesterolemia* (n=2701) [0.47, 0.91] 0.52 No hypercholesterolemia* (n=852) [0.30, 0.92] BMI 30 (n=1758) [0.45, 0.98] 0.63 BMI < 30 (n=1853) [0.38, 0.87] Stable angina (n=2085) [0.39, 0.81] 0.44 No stable angina (n=1458) [0.45, 1.11] SPIRIT IV Subgroup Analysis: TLF at 1 Year TLF = cardiac death, target vessel MI, or ischemia-driven TLR; 1 Year = 365 ± 28 days. *Requiring medication EES better PES better

30 Group EES (%) PES (%) Relative Risk (95% CI) Relative Risk (95% CI) P interaction All randomized (n=3687) [0.46, 0.82] Single lesion treated (n=2710) [0.48, 0.96] 0.34 Two or more lesions treated (n=901) [0.32, 0.83] RVD > 2.75 mm (n=1351) [0.49, 1.41] 0.29 RVD 2.75 mm (n=1352) [0.35, 0.91] Lesion length > 13.3 mm (n=1346) [0.41, 1.03] 0.79 Lesion length 13.3 mm (n=1349) [0.41, 1.23] Bailout stent required (n=221) [0.14, 0.86] 0.19 No bailout stent required (n=3390) [0.48, 0.87] Diabetes (n=1140) [0.59, 1.49] 0.02 No diabetes(n=2467) [0.32, 0.68] SPIRIT IV Subgroup Analysis: TLF at 1 Year 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 EES better PES better

31 RR [95%CI] = 0.47 [0.32, 0.68] p< /76126/37952/165255/815 RR [95%CI] = 0.94 [0.59, 1.49] p=0.80 XIENCE VTAXUS Impact of Diabetes on TLF TLF (%) P interaction = 0.02 TLF = cardiac death, target vessel MI, or ischemia-driven TLR

32 Clinical Outcomes Through 1 Year - No Diabetes Mellitus - XIENCE V 1669 pts TAXUS 829 pts P value Death, all0.8%1.5% Cardiac death0.2%0.5%0.23 MI, all1.5%2.8% Target vessel MI1.5%2.7%0.04 Cardiac death or TV-MI1.6%2.9%0.04 TLR1.8%4.5%< TLF3.1%6.7%< MACE3.2%6.7%< TVF4.3%7.6% ST, protocol0%0.62%0.004 ST, ARC def/prob0.06%1.00% 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 XIENCE V 786 pts TAXUS 399 pts P value Death, all1.6%0.8% Cardiac death0.9%0.3%0.28 MI, all2.6%3.7% Target vessel MI2.6%3.4%0.46 Cardiac death or TV-MI3.4%3.7%0.87 TLR4.2%4.7%0.65 TLF6.4%6.9%0.80 MACE6.4%7.1%0.71 TVF8.4% 1.00 ST, protocol0.53%1.33%0.17 ST, ARC def/prob0.80%1.33%0.52 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 Clinical Outcomes Through 1 Year - Diabetes Mellitus -

34 XIENCE VTAXUS Impact of Diabetes Type on TLF TLF (%) P interaction = 0.56 TLF = cardiac death, target vessel MI, or ischemia-driven TLR 16/1998/11533/56218/264 RR [95%CI] = 0.86 [0.49, 1.50] p=0.64 RR [95%CI] = 1.16 [0.51, 2.62] p=0.83 Diabetes not requiring insulin Diabetes requiring insulin

35 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 SPIRIT IV Conclusions

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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