TAXUS Landmark Analysis Impact of Long-Term Clopidogrel Usage on Death, Myocardial Infarction and...

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.


Objective

We performed a similar examination of TAXUS stent in the prospective, randomized, double-blind TAXUS trials.


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)


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


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


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


Impact of Thienopyridine Use onDeath or MI to 5-Years


5%5%

0%0%

10%10%

Cum

ulat

ive

Eve

nt R

ate


15%15%

2y2y 3y3y 4y4y 5y5y1y1yIndex

Procedure

0-1 yr Events0-1 yr Events(all patients)(all patients)


P=0.75

P=0.28

Event-Free

0%

5%

10%

15%


Event Rate

0%

5%

10%

15%

Days After 1 Year0 365 730 1095 1460


Impact of Thienopyridine Use onStent Thrombosis* to 2-Years


5%5%

0%0%

10%10%

Cum

ulat

ive

Eve

nt R

ate


15%15%

2y2y1y1yIndex

Procedure

0-1 yr Events0-1 yr Events(All patients)(All patients)

*ARC Definite/Probable

Event-Free

0%

5%

10%

15%


Event Rate

0%

5%

10%

15%



P=0.07

P=0.25


Impact of Thienopyridine Use onStent Thrombosis* to 5-Years


5%5%

0%0%

10%10%

Cum

ulat

ive

Eve

nt R

ate


15%15%


Procedure



Event-Free

0%

5%

10%

15%


Event Rate

0%

5%

10%

15%

Days After 1 Year0 365 730 1095 1460


P=0.43

P=0.59


Impact of Thienopyridine Use onDeath, MI, or Stent Thrombosis* to 2-Years


5%5%

0%0%

10%10%

Cum

ulat

ive

Eve

nt R

ate


15%15%

2y2y1y1yIndex

Procedure



Event-Free

0%

5%

10%

15%


Event Rate

0%

5%

10%

15%



P=0.82

P=0.51


Impact of Thienopyridine Use onDeath, MI, or Stent Thrombosis* to 5-Years


5%5%

0%0%

10%10%

Cum

ulat

ive

Eve

nt R

ate


15%15%


Procedure




P=0.75

P=0.28

Event-Free

0%

5%

10%

15%


Event Rate

0%

5%

10%

15%

Days After 1 Year0 365 730 1095 1460


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)


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

TAXUS Landmark Analysis Impact of Long-Term Clopidogrel Usage on Death, Myocardial Infarction and...

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