Post on 14-Jan-2016
TAXUS Landmark Analysis
Impact of Long-Term Clopidogrel
Usage on Death, Myocardial Infarction and
Stent Thrombosis
TAXUS Landmark Analysis
Impact of Long-Term Clopidogrel
Usage on Death, Myocardial Infarction and
Stent Thrombosis
Gregg W. Stone, MD
Stephen G. Ellis, Antonio Colombo, David F. Kong, Mark I. Friedman, Donald S. Baim
Gregg W. Stone, MD
Stephen G. Ellis, Antonio Colombo, David F. Kong, Mark I. Friedman, Donald S. Baim
TAXUS II-SR (5y), IV (5y), V de novo (3y) Thienopyridine Landmark Analysis – G. Stone - TAXUS II-SR (5y), IV (5y), V de novo (3y) Thienopyridine Landmark Analysis – G. Stone - 33TCT – October 23, 2007 – Late Breaking TrialTCT – October 23, 2007 – Late Breaking Trial
Thienopyridine Landmark Study
JAMA. 2007 Jan 10;297(2):159-68.
Non-blinded, observational landmark study from uncontrolled registry data
Thienopyridine Use >1yr
May reduce death and MI in patients who have received drug-eluting
stents.
TAXUS II-SR (5y), IV (5y), V de novo (3y) Thienopyridine Landmark Analysis – G. Stone - TAXUS II-SR (5y), IV (5y), V de novo (3y) Thienopyridine Landmark Analysis – G. Stone - 55TCT – October 23, 2007 – Late Breaking TrialTCT – October 23, 2007 – Late Breaking Trial
Objective
We performed a similar examination of TAXUS stent in the prospective, randomized, double-blind TAXUS trials.
TAXUS II-SR (5y), IV (5y), V de novo (3y) Thienopyridine Landmark Analysis – G. Stone - TAXUS II-SR (5y), IV (5y), V de novo (3y) Thienopyridine Landmark Analysis – G. Stone - 66TCT – October 23, 2007 – Late Breaking TrialTCT – October 23, 2007 – Late Breaking Trial
Analysis Design
Patients free of Death, MI, TVR, or ARC ST* at 1-year (n=2171)
ON (T+)Thienopyridine
n=447
ON (T+)Thienopyridine
n=517
OFF (T-)Thienopyridine
n=624
OFF (T-)Thienopyridine
n=583
Subsequent events tabulated (to 2 years and 5 years)
BMS (n=1030) TAXUS (n=1141)
*Academic Research Consortium (Cutlip et al., Circulation 115:2344)
TAXUS II-SR (5y), IV (5y), V de novo (3y) Thienopyridine Landmark Analysis – G. Stone - TAXUS II-SR (5y), IV (5y), V de novo (3y) Thienopyridine Landmark Analysis – G. Stone - 88TCT – October 23, 2007 – Late Breaking TrialTCT – October 23, 2007 – Late Breaking Trial
Baseline Results in TAXUS Patients
OFF (n=624) ON (n=517) P Value
Age (years) 63.1±10.9 62.3±11.2 0.21
Male, % (n) 71.0 (443) 73.1 (378) 0.47
Diabetic, % (n) 19.9 (124) 29.4 (152) 0.0002
Insulin-requiring, % (n) 5.4 (34) 7.9 (41) 0.09
Current Smoker, % (n) 22.6 (141) 21.5 (111) 0.67
Total # of Stents 1.1±0.4 1.3±0.5 <0.0001
Total Stent Length (mm) 22.0±9.4 25.4±11.8 <0.0001
RVD (mm) 2.75±0.50 2.7±0.5 0.75
Lesion Length (mm) 13.7±7.0 15.5±8.0 0.0001
MLD (mm) 0.9±0.3 0.9±0.4 0.44
Diameter Stenosis (%) 66.8±10.6 7.4±11.3 0.34
TAXUS II-SR (5y), IV (5y), V de novo (3y) Thienopyridine Landmark Analysis – G. Stone - TAXUS II-SR (5y), IV (5y), V de novo (3y) Thienopyridine Landmark Analysis – G. Stone - 99TCT – October 23, 2007 – Late Breaking TrialTCT – October 23, 2007 – Late Breaking Trial
Baseline Results in BMS Patients
OFF (n=583) ON (n=447) P Value
Age (years) 61.8±10.8 62.5±10.4 0.29
Male, % (n) 71.5 (417) 73.2 (327) 0.58
Diabetic, % (n) 23.2 (135) 26.2 (117) 0.27
Insulin-requiring, % (n) 8.2 (48) 6.5 (29) 0.34
Current Smoker, % (n) 21.4 (125) 20.1 (90) 0.64
Total # of Stents 1.1±0.4 1.2±0.5 0.03
Total Stent Length (mm) 21.6±9.2 24.5±11.4 <0.0001
RVD (mm) 2.78±0.51 2.73±0.51 0.08
Lesion Length (mm) 13.9±7.0 15.0±8.3 0.02
MLD (mm) 0.9±0.4 0.9±0.4 0.13
Diameter Stenosis (%) 66.2±10.9 66.9±11.7 0.33
TAXUS II-SR (5y), IV (5y), V de novo (3y) Thienopyridine Landmark Analysis – G. Stone - TAXUS II-SR (5y), IV (5y), V de novo (3y) Thienopyridine Landmark Analysis – G. Stone - 1313TCT – October 23, 2007 – Late Breaking TrialTCT – October 23, 2007 – Late Breaking Trial
Impact of Thienopyridine Use onDeath or MI to 2-Years
Events After 1 YearEvents After 1 Year(in patients death/MI/ST/TVR free at 1 year)(in patients death/MI/ST/TVR free at 1 year)
5%5%
0%0%
10%10%
Cum
ulat
ive
Eve
nt R
ate
Event Rate ± 1.5 SE, Log-Rank p valueEvent Rate ± 1.5 SE, Log-Rank p value
15%15%
2y2y1y1yIndex
Procedure
0-1 yr Events0-1 yr Events(all patients)(all patients)
Event-Free
0%
5%
10%
15%
Days After Procedure0 365
Event Rate
0%
5%
10%
15%
Days After 1 Year0 365
PES (T+): 1.8% (9)PES (T-): 1.9% (12)BMS (T+): 2.5% (11)BMS (T-): 1.9% (11)
P=0.82
P=0.51
TAXUS II-SR (5y), IV (5y), V de novo (3y) Thienopyridine Landmark Analysis – G. Stone - TAXUS II-SR (5y), IV (5y), V de novo (3y) Thienopyridine Landmark Analysis – G. Stone - 1414TCT – October 23, 2007 – Late Breaking TrialTCT – October 23, 2007 – Late Breaking Trial
Impact of Thienopyridine Use onDeath or MI to 5-Years
Events After 1 YearEvents After 1 Year(in patients death/MI/ST/TVR free at 1 year)(in patients death/MI/ST/TVR free at 1 year)
5%5%
0%0%
10%10%
Cum
ulat
ive
Eve
nt R
ate
Event Rate ± 1.5 SE, Log-Rank p valueEvent Rate ± 1.5 SE, Log-Rank p value
15%15%
2y2y 3y3y 4y4y 5y5y1y1yIndex
Procedure
0-1 yr Events0-1 yr Events(all patients)(all patients)
PES (T+): 8.3% (35)PES (T-): 9.8% (51)BMS (T+): 7.9% (25)BMS (T-): 9.2% (48)
P=0.75
P=0.28
Event-Free
0%
5%
10%
15%
Days After Procedure0 365
Event Rate
0%
5%
10%
15%
Days After 1 Year0 365 730 1095 1460
TAXUS II-SR (5y), IV (5y), V de novo (3y) Thienopyridine Landmark Analysis – G. Stone - TAXUS II-SR (5y), IV (5y), V de novo (3y) Thienopyridine Landmark Analysis – G. Stone - 1515TCT – October 23, 2007 – Late Breaking TrialTCT – October 23, 2007 – Late Breaking Trial
Impact of Thienopyridine Use onStent Thrombosis* to 2-Years
Events After 1 YearEvents After 1 Year(in patients death/MI/ST/TVR free at 1 year)(in patients death/MI/ST/TVR free at 1 year)
5%5%
0%0%
10%10%
Cum
ulat
ive
Eve
nt R
ate
Event Rate ± 1.5 SE, Log-Rank p valueEvent Rate ± 1.5 SE, Log-Rank p value
15%15%
2y2y1y1yIndex
Procedure
0-1 yr Events0-1 yr Events(All patients)(All patients)
*ARC Definite/Probable
Event-Free
0%
5%
10%
15%
Days After Procedure0 365
Event Rate
0%
5%
10%
15%
Days After 1 Year0 365
PES (T+): 0.0% (0)PES (T-): 0.7% (4)BMS (T+): 0.2% (1)BMS (T-): 0.0% (0)
P=0.07
P=0.25
TAXUS II-SR (5y), IV (5y), V de novo (3y) Thienopyridine Landmark Analysis – G. Stone - TAXUS II-SR (5y), IV (5y), V de novo (3y) Thienopyridine Landmark Analysis – G. Stone - 1616TCT – October 23, 2007 – Late Breaking TrialTCT – October 23, 2007 – Late Breaking Trial
Impact of Thienopyridine Use onStent Thrombosis* to 5-Years
Events After 1 YearEvents After 1 Year(in patients death/MI/ST/TVR free at 1 year)(in patients death/MI/ST/TVR free at 1 year)
5%5%
0%0%
10%10%
Cum
ulat
ive
Eve
nt R
ate
Event Rate ± 1.5 SE, Log-Rank p valueEvent Rate ± 1.5 SE, Log-Rank p value
15%15%
2y2y 3y3y 4y4y 5y5y1y1yIndex
Procedure
0-1 yr Events0-1 yr Events(All patients)(All patients)
*ARC Definite/Probable
Event-Free
0%
5%
10%
15%
Days After Procedure0 365
Event Rate
0%
5%
10%
15%
Days After 1 Year0 365 730 1095 1460
PES (T+): 0.8% (4)PES (T-): 1.4% (8)BMS (T+): 0.2% (1)BMS (T-): 0.7% (3)
P=0.43
P=0.59
TAXUS II-SR (5y), IV (5y), V de novo (3y) Thienopyridine Landmark Analysis – G. Stone - TAXUS II-SR (5y), IV (5y), V de novo (3y) Thienopyridine Landmark Analysis – G. Stone - 1717TCT – October 23, 2007 – Late Breaking TrialTCT – October 23, 2007 – Late Breaking Trial
Impact of Thienopyridine Use onDeath, MI, or Stent Thrombosis* to 2-Years
Events After 1 YearEvents After 1 Year(in patients death/MI/ST/TVR free at 1 year)(in patients death/MI/ST/TVR free at 1 year)
5%5%
0%0%
10%10%
Cum
ulat
ive
Eve
nt R
ate
Event Rate ± 1.5 SE, Log-Rank p valueEvent Rate ± 1.5 SE, Log-Rank p value
15%15%
2y2y1y1yIndex
Procedure
0-1 yr Events0-1 yr Events(All patients)(All patients)
*ARC Definite/Probable
Event-Free
0%
5%
10%
15%
Days After Procedure0 365
Event Rate
0%
5%
10%
15%
Days After 1 Year0 365
PES (T+): 1.8% (9)PES (T-): 1.9% (12)BMS (T+): 2.5% (11)BMS (T-): 1.9% (11)
P=0.82
P=0.51
TAXUS II-SR (5y), IV (5y), V de novo (3y) Thienopyridine Landmark Analysis – G. Stone - TAXUS II-SR (5y), IV (5y), V de novo (3y) Thienopyridine Landmark Analysis – G. Stone - 1818TCT – October 23, 2007 – Late Breaking TrialTCT – October 23, 2007 – Late Breaking Trial
Impact of Thienopyridine Use onDeath, MI, or Stent Thrombosis* to 5-Years
Events After 1 YearEvents After 1 Year(in patients death/MI/ST/TVR free at 1 year)(in patients death/MI/ST/TVR free at 1 year)
5%5%
0%0%
10%10%
Cum
ulat
ive
Eve
nt R
ate
Event Rate ± 1.5 SE, Log-Rank p valueEvent Rate ± 1.5 SE, Log-Rank p value
15%15%
2y2y 3y3y 4y4y 5y5y1y1yIndex
Procedure
0-1 yr Events0-1 yr Events(All patients)(All patients)
*ARC Definite/Probable
PES (T+): 8.3% (35)PES (T-): 9.8% (51)BMS (T+): 7.9% (25)BMS (T-): 9.2% (48)
P=0.75
P=0.28
Event-Free
0%
5%
10%
15%
Days After Procedure0 365
Event Rate
0%
5%
10%
15%
Days After 1 Year0 365 730 1095 1460
TAXUS II-SR (5y), IV (5y), V de novo (3y) Thienopyridine Landmark Analysis – G. Stone - TAXUS II-SR (5y), IV (5y), V de novo (3y) Thienopyridine Landmark Analysis – G. Stone - 2020TCT – October 23, 2007 – Late Breaking TrialTCT – October 23, 2007 – Late Breaking Trial
Thienopyridine Use and Stent Thrombosisin TAXUS-treated Patients
766
924
934
974
410
498
522
711
1019
1024
1241
1334
Time Post-Procedure
1 Yr 2 Yrs 3 Yrs 4 Yrs 5 Yrs
Individual ST Patients (each bar represents 1 patient)
Procedure
Off ThienopyridineOn Thienopyridine
ONat
1 Yr
OFFat
1 Yr
(days to ST)
TAXUS II-SR (5y), IV (5y), V de novo (3y) Thienopyridine Landmark Analysis – G. Stone - TAXUS II-SR (5y), IV (5y), V de novo (3y) Thienopyridine Landmark Analysis – G. Stone - 2121TCT – October 23, 2007 – Late Breaking TrialTCT – October 23, 2007 – Late Breaking Trial
Conclusions
Patients on thienopyridines at 1 year are more likely to remain on it at 5 years
Patients on thienopyridines at 1 year display a trend toward fewer safety events through 5 years – a trend that does not reach statistical significance
It is impossible to attribute any observed benefit to thienopyridine use itself (rather than to disease-specific factors) given the significant differences at baseline
Benefit in other high-risk groups not examined in this analysis cannot be excluded e.g. CTO, AMI, etc.
This analysis does not provide clear evidence for routinely extending thienopyridine use beyond 1 year