1. Comparison of Everolimus-Eluting and Paclitaxel-Eluting Stents: First Report of the Five-Year Clinical Outcomes from the SPIRIT III Trial
Gregg W. Stone, MD
Poornima Sood MD, MBA; Robert J. Applegate MD; Manejeh Yaqub MD; James B. Hermiller MD; William Newman MD; Mark Sanz MD; Sherry Cao MS; Susan Bezenek RN; Jerome E Williams MD; Alexandra Lansky MD; Donald E. Cutlip MD, and Krishnankutty Sudhir MD, PhD
for the SPIRIT III Investigators 1

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

3. Background
In the SPIRIT III trial (1,002 randomized patients), the XIENCE V everolimus-eluting stent compared to the TAXUS Express paclitaxel-eluting stent resulted in:
Significantly reduced angiographic late loss at 8 months (co-primary endpoint)
Non-inferior rates of TVF at 1 year (co-primary endpoint)
Significantly reduced rates of MACE at 1 year, with the curves diverging over time
Non-significant differences in stent thrombosis at 1 year
Five-year clinical outcomes have not yet been reported 3 3 3

4. Study Algorithm XIENCE V TAXUS Express
1002 pts enrolled at 65 U.S sites
RVD ≥2.5 mm - ≤3.75 mm; Lesion length ≤28 mm
Max. 2 lesions each in a different epicardial vessel
Pre-rand: ASA ≥300 mg, clopidogrel ≥300 mg load unless on chronic Rx
Randomized 2:1 XIENCE V:TAXUS Express
Stratified by diabetes and intent for 1 vs. 2 lesion treatment
Pre-dilatation mandatory
Everolimus-eluting
XIENCE V
Paclitaxel-eluting
TAXUS Express
Aspirin ≥ 80 mg QD for 5 years; Clopidogrel 75mg QD for ≥6 months
Clinical f/u: 1, 6, 9 months and yearly for 1-5 years
Angio f/u 8 months; IVUS f/u 8 months

5. Baseline Demographics
XIENCE V 669 pts
TAXUS 333 pts
p value
Age (in years)
63.2 ± 10.5
62.8 ± 10.2
0.54
Male (%)
70.1
65.7
0.17
Hypertension (%)
76.2
74.0
0.48
Hypercholesterolemia (%)
74.2
71.5
0.36
Diabetes mellitus (%)
29.6
27.9
0.60
Insulin requiring (%)
7.8
5.5
0.19
Current smoker (%)
23.4
22.5
0.81
Prior MI (%)
19.9
18.0
0.49
Unstable angina (%)
18.7
25.1
0.02 5

6. Baseline Angiography XIENCE V 772 lesions TAXUS 383 lesions p value
Lesion location
LAD
41.3%
42.9%
0.61
LCX
27.6%
28.3%
0.83
RCA
31.0%
28.5%
0.41
LMCA
0.1%
0.3%
0.55
QCA
RVD (mm)
2.77 ± 0.45
2.76 ± 0.46
0.87
MLD (mm)
0.82 ± 0.41
0.83 ± 0.40
0.79
% DS
70.0 ±13.3
69.4 ±13.6
0.54
Lsn length (mm)
14.7 ± 5.6
14.7 ± 5.7
0.92 6

7. Patient Flow and Follow-up
Randomized
(N=1,002)
XIENCE V
(N=669)
TAXUS
(N=333)
Lost to f/u = 7
Patient withdrawal = 5
8 = Lost to f/u
5 = Patient withdrawal
1-year follow-up*
(N=977; 97.5%)
XIENCE V
(N=657)
TAXUS
(N=320)
Lost to f/u = 8
Patient withdrawal = 6
3 = Lost to f/u
4 = Patient withdrawal
2-year follow-up*
(N=956; 95.4%)
XIENCE V
(N=643)
TAXUS
(N=313)
Lost to f/u = 10
Patient withdrawal = 3
3 = Lost to f/u
0 = Patient withdrawal
3-year follow-up*
(N=940; 93.8%)
XIENCE V
(N = 630)
TAXUS
(N = 310)
Lost to f/u = 3
Patient withdrawal = 0
4 = Lost to f/u
0 = Patient withdrawal
1 “other” in 5-year Patient Flow that needs to be accounted for
4-year follow-up*
(N=933; 93.1%)
XIENCE V
(N = 627)
TAXUS
(N = 306)
Lost to f/u = 4
Patient withdrawal = 2
4 = Lost to f/u
2 = Patient withdrawal
5-year follow-up*
(N=921; 91.9%)
XIENCE V
(N = 621)
TAXUS
(N = 300)
*F/U window ± 28 days 7

8. Antiplatelet Agent Utilization
XIENCE V 669 pts
TAXUS 333 pts
p value
Aspirin
- At 1 year
96.7%
96.8%
1.00
- At 2 years
95.3%
94.7%
0.75
- At 3 years
93.3%
93.9%
0.78
- At 4 years
91.4%
94.4%
0.14
- At 5 years
89.6%
93.2%
0.10
Thienopyridine
71.2%
70.6%
0.88
56.4%
61.2%
0.18
51.4%
52.2%
0.83
49.0%
47.5%
0.72
44.2%
44.0%
Pvalues: T38-A_PPClopTiclop 8

9. Composite Safety and Efficacy Through 5 Years
XIENCE V (n=669)
TAXUS Express (n=333)
RR [95% CI] =
0.77 [0.60, 0.98]
p=0.04
RR [95% CI] =
0.65 [0.48, 0.88]
p=0.008
RR [95% CI] =
0.65 [0.49, 0.87]
p=0.005
Rate (%)
Pvalues: DrSp3_AH1_T04_Hi_IschAE_TLF_5Y_XT
TVF
TLF
MACE
TVF = cardiac death, MI, or ID-TVR; MACE = cardiac death, MI, or ID-TLR;
TLF = cardiac death, target vessel MI, or ID-TLR;
Categorical data, 1825 ± 28 days

10. Target Vessel Failure Through 5 Years
40%
5-year HR
TAXUS Express (n=332)
XIENCE V (n=669)
0.76 [0.57, 1.01]
35%
p=0.05
30%
1-year HR
24.5%
25%
0.73 [0.48, 1.10]
TVF (%)
p=0.13
Δ5.2%
20%
19.3%
15%
10.8%
10%
Δ2.5% 5%
8.3% 0% 6 12 18 24 30 36 42 48 54 60
Months
Number at risk
XIENCE V
669
638
598
581
558
543
532
513
498
490
481
TAXUS
332
308
283
267
257
248
241
234
228
220
210
TVF (co-primary endpoint) = cardiac death, MI, or ischemic-driven TVR

11. Target Lesion Failure Through 5 Years
TAXUS Express (n=332)
XIENCE V (n=669)
30%
5-year HR
0.64 [0.46, 0.89]
25%
p=0.008
1-year HR
20%
19.0%
0.56 [0.34, 0.90]
p=0.01
TLF (%)
Δ6.3%
15%
9.2%
12.7%
10%
Δ3.8% 5%
5.4% 0% 6 12 18 24 30 36 42 48 54 60
Months
Number at risk
XIENCE V
669
646
616
601
582
571
565
548
537
529
521
TAXUS
332
310
288
274
269
262
255
248
243
231
223
TLF = cardiac death, target vessel MI, or ischemic-driven TLR

12. Major Adverse Cardiac Events Through 5 Years
5-year HR
TAXUS Express (n=332)
XIENCE V (n=669)
30%
0.64 [0.46, 0.89]
p=0.007
25%
1-year HR
20.2%
20%
0.58 [0.37, 0.92]
Δ6.5%
p=0.02
MACE (%)
15%
9.9%
13.7%
10%
Δ4.0% 5%
5.9% 0% 6 12 18 24 30 36 42 48 54 60
Months
Number at risk
XIENCE V
669
644
613
597
578
566
559
542
531
524
515
TAXUS
332
309
286
272
266
258
251
244
240
229
221
MACE = cardiac death, MI, or ischemic-driven TLR

13. Ischemia-driven TLR Through 5 Years
TAXUS Express (n=332)
XIENCE V (n=669)
25%
5-year HR
0.69 [0.46, 1.05]
20%
p=0.08
1-year HR
15%
0.62 [0.33, 1.14]
TLR (%)
p=0.12
12.1%
10%
Δ3.5%
5.6%
8.6% 5%
Δ2.1%
3.5% 0% 6 12 18 24 30 36 42 48 54 60
Months
Number at risk
XIENCE V
669
652
624
609
591
580
575
557
545
537
529
TAXUS
332
318
297
285
281
275
268
261
256
244
234

14. All-Cause Death Through 5 Years
5-year HR
15%
TAXUS Express (n=332)
XIENCE V (n=669)
0.57 [0.36, 0.93]
p=0.02
12%
10.1% 9%
Death (%)
Δ4.2%
1-year HR 6%
0.98 [0.29, 3.25]
p=0.97
5.9% 3%
1.2%
Δ0%
1.2% 0% 6 12 18 24 30 36 42 48 54 60
Months
Number at risk
XIENCE V
669
661
646
632
618
612
609
598
590
584
578
TAXUS
332
324
315
306
303
300
296
287
284
274
266 14

15. Myocardial Infarction Through 5 Years
TAXUS Express (n=332)
XIENCE V (n=669)
10%
5-year HR
0.68 [0.38, 1.20]
p=0.18 8%
1-year HR
0.67 [0.33, 1.38]
6.3%
p=0.28 6%
MI (%)
Δ1.9%
3.7% 4%
4.4%
Δ1.1% 2%
2.6% 0% 6 12 18 24 30 36 42 48 54 60
Months
Number at risk
XIENCE V
669
653
631
616
600
592
586
575
568
562
555
TAXUS
332
315
304
291
286
281
277
268
266
257
250

16. All-Cause Death or MI Through 5 Years
TAXUS Express (n=332)
XIENCE V (n=669)
25%
5-year HR
0.62 [0.42, 0.90]
p=0.01
20%
1-year HR
15.1%
15%
0.73 [0.39, 1.37]
Death or MI (%)
p=0.33
Δ5.6%
10%
4.6%
9.5% 5%
Δ1.1%
3.5% 0% 6 12 18 24 30 36 42 48 54 60
Months
Number at risk
XIENCE V
669
653
631
616
600
592
586
575
568
562
555
TAXUS
332
315
304
291
286
281
277
268
266
257
250

17. Components of Safety and Efficacy Through 5 Years
XIENCE V (n=669)
19.0
TAXUS Express (n=333)
p=0.10
p=0.19
Rate (%)
p=0.15
p=0.23
p=0.20
Cardiac death, MI from Pvalues: T03_Nhi_IschAE_5Y_XT
TV-MI from Sp3_RCT_5Y_TCT2011: AH1_T08_TLF_5Y_XT
TLR, TVR remote, TVR from T06, p21 of Sp3_RCT_5Y_Tables_Pvalues.pdf
Cardiac death
TV-MI
All MI
TLR
TVR remote
TVR
TLR, TVR, TVR remote are ischemia-driven
Categorical data, 1825 ± 28 days

18. Stent Thrombosis (Protocol Definition)*
Through 5 Years 5%
TAXUS Express (n=332)
XIENCE V (n=669)
5-year HR 4%
0.81 [0.29, 2.23]
p=0.68 3%
1-year HR
Stent Thrombosis (%)
1.23 [0.24, 6.34]
2.0%
p=0.80 2%
Δ0.4%
1.6% 1%
0.8%
Δ-0.2%
0.6% 0% 6 12 18 24 30 36 42 48 54 60
Number at risk
XIENCE V
669
659
642
628
613
607
604
592
584
578
572
TAXUS
332
324
314
303
300
297
293
284
281
271
263
Months
*ACS + angio thrombus, or unexplained death or STEMI/Q-wave MI in TL distribution w/i 30 days

19. Stent Thrombosis (Protocol Definition)* Through 5 Years
Early (0 – 30 days)
Late (31 days – 1 year)
Very Late ( > 1 year)
XIENCE V
N=669
1.62%
0.45
0.30
0.81
p=0.48
TAXUS
N=333
2.02%
0.63
1.35
Pvalues: T39-ST-5Y
Stent thrombosis (%)
*ACS + angiographic thrombus, or unexplained death or STEMI/Q-wave MI in TL distribution within 30 days
Categorical data, 1825 ± 28 days

20. Stent Thrombosis (ARC Definite/Probable) Through 5 Years5%
TAXUS Express (n=332)
XIENCE V (n=669) 4%
5-year HR
0.88 [0.29, 2.63] 3%
1-year HR
p=0.82
Stent Thrombosis (%)
1.48 [0.30, 7.32]
p=0.63 2%
1.6%
Δ0.2%
0.9% 1%
1.4%
Δ-0.6%
0.3% 0% 6 12 18 24 30 36 42 48 54 60
Months
Number at risk
XIENCE V
669
659
642
628
613
607
604
592
584
578
572
TAXUS
332
324
315
304
299
296
292
283
280
270
263

21. Stent Thrombosis (ARC Definite/Probable) Through 5 Years
Early (0 – 30 days)
Late (31 days – 1 year)
Very Late ( > 1 year)
XIENCE V
N=669
1.46%
0.45
0.46
0.49
p=0.22
TAXUS
N=333
1.68%
0.31
1.35
Pvalues: T39
Stent thrombosis (%)

22. Conclusions
In the SPIRIT III trial at 5 years (powered to demonstrate noninferiority), treatment with the XIENCE V everolimus- eluting stent compared to the TAXUS Express paclitaxel- eluting stent resulted in:
Significantly reduced rates of the composite safety and efficacy measures of TVF, TLF and MACE
Significantly reduced rate of all-cause death, with non- significantly different rates of MI, ID-TLR and stent thrombosis
No evidence of late catch-up in ID-TLR
Trials with greater numbers of pts (SPIRIT IV) and/or more complex lesions (COMPARE) are required to examine the relative differences in low frequency event rates between these 2 stents