SPIRIT IV A Prospective, Randomized Trial Comparing an EverolimusEluting Stent and a PaclitaxelEluti

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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

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Disclosures

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

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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

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SPIRIT IV Study Algorithm

• 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 21 XIENCE VTAXUS
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
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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 gt50 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

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SPIRIT III / SPIRIT IV Differences
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SPIRIT IV Major 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
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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) Vanderbil
  t, 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

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SPIRIT IV Top 20 Enrollers
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SPIRIT IV Patient Flow
Enrolled (N3690)
3 Randomization errors
Randomized (N3687)
TAXUS(N1229)
XIENCE V (N2458)
Lost to f/u 35 Withdrawal 7 Other 0
24 Lost to f/u 8 Withdrawal 2 Other
1-Year Follow-up(N3611 97.9)
TAXUS(N1195)
XIENCE V (N2416)
F/U window 28 days
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Baseline Demographics
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Baseline Angiography
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Procedural Results
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Antiplatelet Agent Utilization
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Primary Endpoint TLF Through 1 Year
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
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TLF Through 1 Year
HR 95CI 0.61 0.46, 0.82
p0.0008
6.6
? 2.7
Target lesion failure ()
3.9
Months
TLF cardiac death, target vessel MI, or
ischemia-driven TLR
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TVF, TLF, and MACE Through 1 Year
RR 95CI 0.71 0.55, 0.92 p0.009
RR 95CI 0.62 0.46, 0.82 p0.0009
RR 95CI 0.62 0.46, 0.82 p0.001

101/2416
82/1195
81/1195
94/1195
135/2416
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
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Major 2 Endpoint ID-TLR Through 1 Year
Ischemia-driven TLR ()
61/2416
55/1195
XIENCE V
TAXUS
1 Year 365 28 days
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Ischemia-Driven TLR Through 1 Year
HR 95CI 0.54 0.38, 0.78
4.5
p0.0008
? 2.2
Ischemia-driven TLR ()
2.3
Months
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Major 2 EP Cardiac Death or TV MI Through 1 Yr
Cardiac death or MI ()
53/2416
38/1195
XIENCE V
TAXUS
TV MI target vessel MI 1 Year 365 28 days
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Cardiac Death or TV MI Through 1 Year
HR 95CI 0.69 0.46, 1.05
p0.08
3.1
? 0.9
Cardiac death or MI ()
2.2
Months
MI Target Vessel MI
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TLF Components Through 1 Year
RR 95CI 0.55 0.38, 0.78 p0.001
RR 95CI 0.62 0.40, 0.96 p0.04

RR 95CI 0.99 0.34, 2.89 p1.00
44/2416
55/1195
35/1195
5/1195
10/2416
61/2416
ID-TLR
Cardiac Death
Target Vessel MI
TLF cardiac death, target vessel MI, or
ischemia-driven TLR 1 Year 365 28 days
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Death and MI at 1 Year
MI Target Vessel MI Non-Target Vessel MI
Categorical data, 365 28 days
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Stent Thrombosis (Protocol Definition)
HR 95CI 0.20 0.06, 0.63
p0.002
Stent thrombosis ()
0.82
? 0.66
0.16
Months
ACS angiographic thrombus, or unexplained
death or STEMI/Q-wave MI in TL distribution
within 30 days
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Stent Thrombosis (Protocol Definition)
XIENCE V N2458
0.17
p0.004
TAXUS N1229
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
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Stent Thrombosis (ARC Def or Prob)
HR 95CI 0.27 0.11, 0.67
p0.003
1.06
Stent thrombosis ()
? 0.77
0.29
Months
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Stent Thrombosis (ARC Definition)
XIENCE V N2458
0.29
p0.004
TAXUS N1229
1.10
Stent thrombosis ()
Definite or Probable per ARC definition Categor
ical data, 365 28 days
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SPIRIT IV 11 Subgroups Examined
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)
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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
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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
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Impact of Diabetes on TLF
RR 95CI 0.47 0.32, 0.68 plt0.0001
RR 95CI 0.94 0.59, 1.49 p0.80
TLF ()
49/761
26/379
52/1652
55/815
TLF cardiac death, target vessel MI, or
ischemia-driven TLR
Pinteraction 0.02
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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
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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
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Impact of Diabetes Type on TLF
RR 95CI 1.16 0.51, 2.62 p0.83
RR 95CI 0.86 0.49, 1.50 p0.64
TLF ()
16/199
8/115
33/562
18/264
Diabetes not requiring insulin
Diabetes requiring insulin
TLF cardiac death, target vessel MI, or
ischemia-driven TLR
Pinteraction 0.56
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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

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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