1. for the SPIRIT IV Investigators
A Large-Scale Randomized Comparison of Everolimus-Eluting and Paclitaxel-Eluting Stents: Three-Year Clinical Outcomes from the SPIRIT IV Trial
Gregg W. Stone, MD
Manejeh Yaqub, MD; Poornima Sood, MD, MBA; Ali Rizvi, MD;
William Newman, MD; Kourosh Mastali, MD; John C. Wang, MD;
Ronald E. Caputo, MD; Kyoko Hattori, RN, BSN; Xiaolu Su, MS;
Charles A. Simonton, MD; Alexandra J. Lansky, MD;
Donald E. Cutlip, MD; Krishnankutty Sudhir MD, PhD;
and Dean J. Kereiakes, MD
for the SPIRIT IV Investigators

2. Disclosures Gregg W. Stone, MD
Consultant to Abbott Vascular, Boston Scientific and Medtronic

3. Background
In SPIRIT IV, the largest clinical trial to date comparing 2 DES, treatment with the XIENCE V everolimus-eluting stent compared to the TAXUS Express paclitaxel-eluting stent resulted in significantly reduced 1-year and 2-year rates of target lesion failure (TLF), ischemia-driven TLR, MI and stent thrombosis.
Whether the benefits of XIENCE V compared to TAXUS Express are sustained at 3 years has not been reported.

4. Study Algorithm XIENCE V TAXUS 3690 pts enrolled at 66 U.S. sites
RVD ≥2.5 mm - ≤3.75 mm; Lesion length ≤28 mm
Max. 3 lesions with a maximum of 2 per epicardial vessel
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
Everolimus-eluting
XIENCE V
Paclitaxel-eluting
TAXUS
Aspirin ≥80 mg QD for 5 years; clopidogrel 75 mg 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 months

6. Patient Flow and Follow-up
XIENCE V
(N=2411)
Randomized
(N=3687)
(N=2458)
TAXUS (N=1229)
1-Year Follow-up* (N=3609; 97.9%)
Lost to f/u = 39
Withdrawal = 8
Other = 0
22 = Lost to f/u
8 = Withdrawal
1 = Other
Enrolled
(N=3690)
3 = Randomization errors
TAXUS (N=1198)
2-Year Follow-up* (N=3539; 96.0%)
(N=2371)
TAXUS (N=1168)
Lost to f/u = 24
Withdrawal = 15
Other = 1
23 = Lost to f/u
7 = Withdrawal
3-Year Follow-up* (N=3506; 95.1%)
(N=2348)
TAXUS (N=1158)
Lost to f/u = 9
Withdrawal = 11
Other = 3
4 = Lost to f/u
6 = Withdrawal
*F/U window: ± 28 days

7. Baseline Demographics
XIENCE V pts
TAXUS pts
P value
Age (in years)
63.3 ± 10.5
63.3 ± 10.2
0.80
Male (%)
67.7
67.8
1.00
Hypertension (%)
77.4
76.1
0.41
Hypercholesterolemia (%)
75.5
0.74
Diabetes mellitus (%)
32.0
32.5
0.79
- Insulin requiring (%)
8.5
9.7
0.24
Current smoker (%)
21.9
22.4
0.70
Prior MI (%)
21.1
19.9
Unstable angina (%)
27.7
28.9
0.46

8. Baseline Angiography XIENCE V 3142 lesions TAXUS 1585 lesions P value
Lesion location
LAD
40.5%
39.8%
0.68
LCX
24.2%
25.4%
0.35
RCA
35.4%
34.8%
LMCA
0.0% -
QCA
RVD (mm)
2.75 ± 0.48
2.75 ± 0.46
0.59
MLD (mm)
0.75 ± 0.38
0.76 ± 0.39
0.36
% DS
72.3 ± 12.6
72.0 ± 12.8
0.44
Lsn length (mm)
14.8 ± 6.7
14.5 ± 6.6
0.24

9. Antiplatelet Agent Utilization
XIENCE V 2458 pts
TAXUS pts P
value
Aspirin
- At 1 year
97.0%
96.8%
0.76
- At 2 years
96.0%
96.2%
0.85
- At 3 years
94.5%
94.9%
0.74
Thienopyridine
94.0%
93.8%
0.82
70.2%
68.1%
0.22
60.3%
1.00 T7

10. Target Lesion Failure Through 3 Years Target lesion failure (%)25
XIENCE V (n=2458)
TAXUS Express (n=1229) 20
HR [95%CI] = [0.63, 0.97]
p=0.004
HR [95%CI] =
0.71 [0.56, 0.90]
p=0.02
p=0.001
HR [95%CI] =
0.61 [0.46, 0.81] 15
11.7%
Target lesion failure (%)
9.9%
Δ 2.5% 10
Δ 2.9%
6.7%
9.2%
Δ 2.7%
7.0% 5
4.0% 3 6 9 12 15 18 21 24 27 30 33 36
Months
Number at risk
XIENCE V
2458
2390
2364
2323
2281
2238
2212
2187
2162
2132
2116
2095
2074
TAXUS
1229
1166
1138
1119
1095
1069
1060
1049
1029
1019
1008
994
979
TLF (primary endpoint at 1 year) = cardiac death, target vessel MI, or ischemia-driven TLR

11. Multivariable Predictors of TLF at 3 Years
Variables
Odds Ratio
[95% CI] P
Value
Presence of thrombus
(Yes vs No)
0.18 [0.04, 0.75]
0.02
RVD
(per 1 mm)
0.60 [0.47, 0.78]
0.0001
ACC/AHA lesion class
(A or B1 vs B2 or C)
0.67 [0.53, 0.84]
0.0006
Treatment
(XIENCE V vs TAXUS)
0.74 [0.58, 0.93]
0.009
Diabetes requiring treatment
1.43 [1.13, 1.82]
0.003
Numbers of diseased vessels (≥2 vs 1)
1.29 [1.03, 1.63]
0.03

12. Ischemia-Driven TLR Through 3 Years Ischemia-driven TLR (%)12
XIENCE V (n=2458)
HR [95%CI] = [0.60, 1.01]
TAXUS Express (n=1229)
HR [95%CI] =
0.65 [0.49, 0.87] 10
p=0.06
p=0.003
7.8%
HR [95%CI] =
0.51 [0.35, 0.73] 8
6.9%
Δ 1.6%
p=0.0002
Ischemia-driven TLR (%) 6
Δ 2.4%
4.6%
6.2% 4
4.5%
Δ 2.4% 2
2.2% 3 6 9 12 15 18 21 24 27 30 33 36
Months
Number at risk
XIENCE V
2458
2420
2395
2355
2314
2271
2248
2225
2202
2172
2156
2136
2116
TAXUS
1229
1186
1159
1140
1116
1090
1081
1070
1051
1041
1033
1019
1005
Major secondary endpoint at 1 year

13. All-cause Death Through 3 Years8
XIENCE V (n=2458)
TAXUS Express (n=1229)
HR [95%CI] = [0.48, 0.93] 7
p=0.02 6
5.1%
HR [95%CI] =
0.80 [0.52, 1.25] 5
p=0.33
Death (%)
HR [95%CI] =
0.86 [0.46, 1.62]
Δ 1.9% 4
2.7% 3
p=0.64
Δ 0.6%
3.2% 2
1.2%
2.1%
Δ 0.2% 1
1.0% 3 6 9 12 15 18 21 24 27 30 33 36
Months
Number at risk
XIENCE V
2458
2431
2417
2392
2362
2335
2323
2315
2302
2279
2272
2261
2250
TAXUS
1229
1207
1199
1187
1169
1147
1143
1139
1127
1118
1113
1102
1089

14. Target Vessel MI Through 3 Years15
XIENCE V (n=2458)
TAXUS Express (n=1229) 12
HR [95%CI] = [0.46, 0.97]
HR [95%CI] = [0.46, 1.03] 9
p=0.03
HR [95%CI] =
0.65 [0.42, 1.02]
Target Vessel MI (%)
p=0.07 6
p=0.06
4.0%
3.4%
2.9%
Δ 1.3% 3
Δ 1.1%
Δ 1.0%
2.7%
2.3%
1.9% 3 6 9 12 15 18 21 24 27 30 33 36
Months
Number at risk
XIENCE V
2458
2393
2378
2350
2319
2292
2277
2266
2251
2227
2218
2207
2194
TAXUS
1229
1180
1167
1155
1137
1116
1110
1106
1093
1084
1074
1062
1048

15. All Death or MI Through 3 Years2 4 6 8 10 12 14 3 9 15 18 21 24 27 30 33 36
XIENCE V (n=2458)
TAXUS Express (n=1229)
HR [95%CI] = [0.52, 0.85]
p=0.001
HR [95%CI] =
0.77 [0.57, 1.04]
9.1%
HR [95%CI] =
0.72 [0.50, 1.03]
p=0.08
Δ 3.2%
All Death or MI (%)
5.9%
p=0.07
Δ 1.4%
4.0%
5.9%
Δ 1.1%
4.5%
2.9%
Months
Number at risk
XIENCE V
2458
2392
2378
2350
2319
2291
2276
2264
2247
2223
2214
2202
2187
TAXUS
1229
1179
1165
1153
1136
1114
1108
1104
1090
1080
1070
1057
1043

16. Clinical Outcomes at 3 Years
XIENCE V (N=2458)
TAXUS
(N=1229)
HR [95%CI]
Log-rank P value
Death, all
3.2%
5.1%
0.66 [0.48, 0.93]
0.02
- Cardiac
1.4%
1.9%
0.76 [0.44, 1.30]
0.31
- Non cardiac
1.8%
3.3%
0.61 [0.40, 0.93]
MI, target vessel
2.7%
4.0%
0.67 [0.46, 0.97]
0.03
MI, all
3.0%
4.6%
0.65 [0.46, 0.93]
- Q-wave
0.3%
0.9%
0.27 [0.10, 0.73]
0.005
- Non Q-wave
2.8%
3.9%
0.72 [0.49, 1.05]
0.08
ID-TLR
6.2%
7.8%
0.78 [0.60, 1.01]
0.06
PCI
5.6%
7.4%
0.74 [0.57, 0.97]
CABG
0.7%
0.89 [0.41, 1.92]
0.76
K-M curves
Rates (%) are Kaplan-Meier estimates 16

17. Stent Thrombosis (Protocol Definition)*6
XIENCE V (n=2458)
TAXUS Express (n=1229) 5
HR [95%CI] = [0.22, 0.75] 4
p=0.02
HR [95%CI] =
0.42 [0.20, 0.92]
p=0.003
Stent thrombosis (%) 3
p=0.01
HR [95%CI] =
0.30 [0.11, 0.82]
1.89% 2
1.17%
Δ 1.12%
0.82% 1
Δ 0.71%
Δ 0.57%
0.25%
0.77%
0.46% 3 6 9 12 15 18 21 24 27 30 33 36
Months
Number at risk
XIENCE V
2458
2427
2413
2387
2358
2331
2319
2311
2295
2272
2264
2254
2242
TAXUS
1229
1199
1189
1178
1160
1140
1134
1130
1118
1109
1101
1089
1076
*ACS + angiographic thrombus, or unexplained death or STEMI/Q-wave MI in TL distribution within 30 days

18. Stent Thrombosis (Protocol Definition)*
Early (0 – 30 days)
Late (>30 days – 1 year)
Very Late (>1 year)
0.08
XIENCE V
N=2458
0.79%
p=0.004
TAXUS
N=1229
1.99%
Stent thrombosis (%)
*ACS + angiographic thrombus, or unexplained death or STEMI/Q-wave MI in TL distribution within 30 days

19. Stent Thrombosis (ARC Def or Prob)4
XIENCE V (n=2458)
TAXUS Express (n=1229)
HR [95%CI] = [0.18, 0.72] 3
HR [95%CI] =
0.36 [0.17, 0.79]
HR [95%CI] =
0.27 [0.11, 0.67]
p=0.003
p=0.008
Stent thrombosis (%) 2
p=0.003
1.60%
1.24%
1.06%
Δ 1.01% 1
Δ 0.82%
Δ 0.77%
0.59%
0.42%
0.29% 3 6 9 12 15 18 21 24 27 30 33 36
Months
Number at risk
XIENCE V
2458
2427
2413
2387
2358
2331
2319
2311
2296
2272
2263
2254
2242
TAXUS
1229
1196
1186
1175
1157
1137
1131
1127
1115
1106
1098
1086
1073

20. Stent Thrombosis (ARC Def or Prob)
Early (0 – 30 days)
Late (>30 days – 1 year)
Very Late (>1 year)
XIENCE V
N=2458
0.13
0.62%
p=0.004
TAXUS
N=1229
1.73%
Stent thrombosis (%)

21. SPIRIT IV: 11 Subgroups Examined
Age ≥ 65 (n=1578)
Diabetes (n=1102)
Age < 65 (n=1928)
No diabetes (n=2400)
Male (n=2390)
Lesion number = Single (n=2633)
Female (n=1116)
Lesion number = Multi (≥2) (n=873)
Hypertension* (n=2705)
Lesion length > median (13.3 mm; n=1308)
No hypertension (n=796)
Lesion length ≤ median (13.3 mm; n=1311)
Hypercholesterolemia* (n=2636)
RVD > median (2.75 mm; n=1314)
No hypercholesterolemia (n=816)
RVD ≤ median (2.75 mm; n=1312)
BMI ≥ 30 (n=1707)
Bailout (n=305)
BMI < 30 (n=1799)
No bailout (n=3201)
Stable angina (n=2030)
No stable angina (n=1412)
RVD and lesion length from the single lesion treated subgroup.
* Requiring medication

22. SPIRIT IV Subgroup Analysis: TLF at 3 Years
Xience V
(%)
Taxus
Relative Risk
(95% CI) P
interaction
All randomized (n=3687)
9.5
11.9
0.80 [0.65, 0.97] —
Age ≥ 65 yrs (n=1578)
9.6
10.4
0.93 [0.68, 1.26]
0.20
Age < 65 yrs (n=1928)
9.4
13.2
0.71 [0.55, 0.93]
Male (n=2390)
11.4
0.84 [0.66, 1.07]
0.46
Female (n=1116)
9.3
12.9
0.72 [0.51, 1.01]
Hypertension* (n=2705)
10.0
12.3
0.82 [0.65, 1.02]
0.65
No hypertension (n=796)
7.6
10.6
0.72 [0.46, 1.13]
Hypercholesterolemia* (n=2636)
9.0
11.7
0.77 [0.61, 0.98]
0.54
No hypercholesterolemia (n=816)
11.0
12.2
0.90 [0.60, 1.34]
BMI ≥ 30 (n=1707)
10.1
0.86 [0.65, 1.14]
BMI < 30 (n=1799)
8.9
12.1
0.74 [0.56, 0.98]
Stable angina (n=2030)
12.7
0.73 [0.56, 0.94]
0.32
No stable angina (n=1412)
11.2
0.90 [0.65, 1.23]
EES better
PES better
TLF = cardiac death, target vessel MI, or ischemia-driven TLR; 2 Years = 730 ± 28 days; *Requiring medication

23. SPIRIT IV Subgroup Analysis: TLF at 3 Years
Xience V
(%)
Taxus
Relative Risk
(95% CI) P
interaction
All randomized (n=3687)
9.5
11.9
0.80 [0.65, 0.97] —
Single lesion treated (n=2633)
8.2
10.6
0.78 [0.60, 0.99]
0.74
Multiple lesions (≥2) treated (n=873)
13.4
15.9
0.84 [0.60, 1.18]
RVD > 2.75 mm (n=1314)
6.7
8.7
0.77 [0.52, 1.14]
1.00
RVD ≤ 2.75 mm (n=1312)
9.8
12.6
0.78 [0.56, 1.07]
Lesion length > 13.3 mm (n=1308)
13.1
0.66 [0.47, 0.92]
0.19
Lesion length ≤ 13.3 mm (n=1311)
7.8
8.5
0.92 [0.63, 1.33]
Bailout (n=305)
12.2
21.7
0.56 [0.33, 0.96]
0.18
No bailout (n=3201)
9.2
11.2
0.83 [0.67, 1.02]
Diabetes (n=1102)
12.4
0.95 [0.68, 1.31]
0.21
No diabetes (n=2400)
11.4
0.72 [0.56, 0.93]
EES better
PES better
TLF = cardiac death, target vessel MI, or ischemia-driven TLR; 2 Years = 730 ± 28 days
Single lesion treated data are used for RVD & lesion length subgroup analyses

24. SPIRIT IV 3-Year Conclusions
In the large-scale, prospective, multicenter, randomized SPIRIT IV trial, the benefits of the XIENCE V everolimus-eluting stent compared to the TAXUS Express paclitaxel-eluting stent present at 1 year and 2 years were sustained at 3 years

25. SPIRIT IV 3-Year Conclusions
With increasing duration of follow-up, the following insights have emerged:
Significant differences in all-cause mortality are apparent at years favoring XIENCE V
Stent thrombosis rates continue to diverge favoring XIENCE V, with a 1% absolute difference in stent thrombosis present at years
The differences between the 2 stent types in ischemia-driven TLR have narrowed, and are no longer significant at 3 years
Consistent relative reductions in TLF with EES were present in 11 pre-specified subgroups, including multiple lesions, long lesions and small vessels
Non-significantly different rates of TLF were present in pts with diabetes, vs a 28% reduction in TLF in pts without diabetes