11/19/2012
DAPT With the XIENCE V
Everolimus-Eluting Coronary
Stent
Dr. Sameh Shaheen
MD, FESC, FSCAI
Prof. of cardiology, Ain shams University
The Egyptian Society of Cardiology
The Working Group of Thrombosis & Hemostasis
The 13th Annual Meeting of the WGTH
28th – 29th June 2012 / Intercontinental City Stars Hotel
Evidence of safety
from the XIENCE V
Trials
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XIENCE – Low ST Rates Continue Beyond 1 Year
XIENCE V demonstrated a low very late stent thrombosis (VLST) rate
of 0.3% between 1 and 3 years in SPIRIT III.
SPIRIT III Landmark Analysis: Very Late Stent Thrombosis Rates
12-Month Data: XIENCE V (0.9%), TAXUS (0.3%), p=0.63
Source: David Cox, SPIRIT III, 3-Year Results, Landmark Analysis, TCT 2009. TAXUS Express2 was the control in SPIRIT III.
.
Consistently Low Stent Thrombosis Rates at 2 Years
Rate of Stent Thrombosis
SPIRIT IV: 2-Year Stent Thrombosis
(ARC Def/Prob)
p=0.008
COMPARE: 2-Year Stent Thrombosis
(ARC Def/Prob)
1.23%
66%
p<0.0001*
0.42%
XIENCE V
N=2458
TAXUS
N=1229
• Largest RCT between two DES to have presented primary
endpoint data
• 3,690 patients
• Clinically-driven primary and secondary endpoints
Source: G. Stone. SPIRIT IV 2-Year Results Presentation. TCT 2010.
Source: P. Smits. COMPARE 2-Year Results Presentation. TCT 2010.
• Investigator-sponsored, single-center, prospective RCT
• 1,800 All Comer, real-world patients
• 11% of XIENCE V patients and 15% of TAXUS patients on
DAPT at 2 years
*Log-rank test
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ISAR-TEST 4 ……2-Year EES vs. SES
Definite Stent Thrombosis
Independently-conducted,
prospective randomized
controlled trial

1,304 patients randomized
1:1(XIENCE: n=652, CYPHER:
n=652)

1.4%
Number of Events

p=0.17
Late (30d-1y)
Early (<30d)
0.6%
Very late (>1y)
Late (30d-1y)
Primary Endpoint: Composite of
Cardiac Death, TV-MI and TLR
Early (<30d)
XIENCE V
CYPHER
XIENCE V had no very late stent thrombosis
Source: R. Byrne. ISAR Test 4 2-Year Results Presentation. TCT 2010.
LESSON I 3-Year
Definite Stent Thrombosis at 3 Years

Late-breaking trial
presented at ESC 2010 of
XIENCE V vs. CYPHER

Investigator-initiated,
single center, independent
study

Propensity-matched, with
1342 patients enrolled in
each arm

Primary endpoint is a
composite of Death, MI
and TVR through 3 years
XIENCE V demonstrates low stent thrombosis rates versus CYPHER
Source: S. Windecker. LESSON I 3-Year Results. ESC 2010.
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Consistently Low Stent Thrombosis Rates in
All-Comers. Trial After Trial.
Stent Thrombosis Rates (ARC Definite)
SORT-OUT IV
LESSON I
COMPARE
RESOLUTE-AC
p*<0.0001
2.7%
p=0.01
p=0.01
1.6%
p=0.05
1.2%
0.7%
0.5%
0.6%
0.3%
0.1%
XIENCE V CYPHER
XIENCE V CYPHER
XIENCE V TAXUS
XIENCE V RESOLUTE
Liberté
9 Months
3 Years
2 Year
1 Year
*Log-rank test
Results from different clinical trials are not directly comparable. Information provided for educational purposes only.
Source: L. Okkels Jensen. SORT OUT 4 9-Month Results Presentation. TCT 2010.
Source: Serruys P et al. Comparison of Zotarolimus-Eluting and Everolimus-Eluting Coronary Stents. New Engl J Med. 2010; 363; 136-46.
Source: P. Smits. COMPARE Two Year Results Presentation. TCT 2010.
Source: S. Windecker. LESSON I 3 Year ResultsPresentation. ESC 2010.
Palmerini T et al.
Lancet 2012: Published On-line
DOI:10.1016/S0140-6736(12)60324-9
49 RCTs; 50,844 pts
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Short- and Long-Term Outcomes With Drug-Eluting and BareMetal Coronary Stents: A Mixed-Treatment Comparison Analysis
of 117 762 Patient-Years of Follow-Up From Randomized Trials
Circulation. 2012;125:2873-2891
•
From 76 randomized clinical trials with 117 762 patient-years of
follow-up, compared with BMS, each DES reduced long-term
target-vessel revascularization (39%–61%), but the magnitude
varied by DES type (EES∼SES∼ZES-R>PES∼ZES>BMS), with a
>42% probability that EES had the lowest target-vessel
revascularization rate.
•
The safest DES appeared to be EES (>86% probability), with
reduction in myocardial infarction and stent thrombosis
compared with BMS.
Do the safety results
correlate with DAPT
discontinuation?
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Consistently Low Stent Thrombosis Rates with
Low DAPT Utilization
COMPARE: 2-Year Stent Thrombosis
(ARC Def/Prob)
Early ST
92% pts on DAPT
Late ST
70% pts on DAPT
Very Late ST
13% pts on DAPT
Source: P. Smits. COMPARE 2-Year Results Presentation. TCT 2010.
Two year cumulative ARC def/prob ST according to
DAPT interruption
Pooled analysis of SPIRIT II,III,IV and COMPARE (n= 6789 pts)
E. Kedhi, ACC2012
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XIENCE – 0% ST Observed After DAPT Interruption
or Discontinuation at 6 Months in All Comers
ARC Def/Prob ST Rates (30 Day – 1 Year) After DAPT Interruption in
XIENCE V USA
Source: Dr. James Hermiller, XIENCE V USA Registry, 1-Year Results, PCR 2010. DAPT interruption and discontinuation
data shown is based on post-hoc analysis.
Timing of 1st DAPT Interruption and any ST through 2 yrs
Xience V patients(n=11,219)
G. Stone, TCT 2011
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Timing of First DAPT Interruption and ST through 1 Year
XIENCE V (N=10,615)
T. Palmerini, PCR 2012
1-Year Target Vessel Failure
Gwon et al. Circ 2012
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PRODIGY
Conclusions—A regimen of 24
months of clopidogrel therapy in
patients who had received a balanced
mixture of DES or BMS was not
significantly more effective than a 6month clopidogrel regimen in reducing
the composite of death due to any
cause, myocardial infarction, or
cerebrovascular accident.
M. Valgimigli, Circ published online March 21, 2012
What do the guidelines tell us for
DAPT usage after DES
Recent data suggest that DAPT for 6 months may
be sufficient because late and very late stent thrombosis
correlate poorly with discontinuation of DAPT
If the risk of morbidity because of bleeding outweights
the anticipated benefit afforded by thienopyridine therapy,
earlier discontinuation should be considered (IIa C)
*: DUKE heart registry, JAMA 07; 159-68
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Conclusion
• Xience as a Second generation DES based on new
platforms, polymer and drug, have shown to be “safe”
and effective in randomized clinical trials.
• These results are confirmed by the real world practice
in registries and all comers trials according to current
definitions.
• Even with the discontinuation of DAPT, Xience has
shown no increased rates of ST in patients treated.
• Based on efficacy & safety results of Xience current
practice has been changed dramatically away from first
generation DES to Second generation DES.
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