Dual Antiplatelet Therapy (DAPT) DurationDilemma: Recent Trials And Guidelines ForClinical Practice

Dean J. Kereiakes, MD FACC FSCAIMedical Director, The Christ Hospital Heart & Vascular Center and the Lindner Research Center at The Christ Hospital, Cincinnati, OhioProfessor of Clinical Medicine, Ohio State University

Dean J. Kereiakes, MD – Disclosure Information

Consulting fees: • Modest: Medpace, HCRI, Ablative

Solutions, Inc.• Significant: Boston Scientific, Abbott

Vascular, REVA Medical Inc.

3

2011 ACC/AHA/SCAI Guideline for PCI

The duration of P2Y12 inhibitor therapy should generally be as follows:

DURATION

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIIIa. In patients receiving a stent (BMS or DES)

during PCI for ACS, P2Y12 inhibitor therapy should be given for at least 12 months. Options include clopidogrel 75 mg daily,prasugrel 10 mg daily or ticagrelor 90mg twice daily

b. In patients receiving DES for non-ACS indication, clopidogrel should be given for at least 12 months if patients are not at high risk for bleeding.

c. In patients receiving BMS for a non-ACS indication, clopidogrel should be given for a minimum of 1 month and ideally up to 12 months (unless patient is at increased risk for bleeding;then it should be given for a minimum of 2 weeks)

Circulation 2011;124:e574-651

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

Randomized Trials of DAPT DurationTrial Patients Test Randomizatio

n 1° EP

Prolonged DAPT Studies

REAL/ZEST Late 2701 DES 1 vs. 2 yrs A vs. A+C

SuperiorityD/MI

2 yrs after rand

DAPTN=20,645

(15,245 DES) (5,400 BMS)

1 vs. 2.5 yrs*A+P vs. DAPT (clop or pras)NI and Sup

D/MI/CVAST, Bleeding

PRODIGY N=1,800 DES, BMS 6 mos vs. 2 yrs A vs. A+C

Superiority D/MI/CVA

Abbreviated DAPT Studies

EXCELLENT N=1,443 SES and EES 6 vs. 12 mos A vs. A+C

Noninferiority D/MI/TVR

ISAR-SAFE** N=6,000DES 6 vs. 12 mos* A+P vs. A+C

NoninferiorityD/MI/CVA/

ST/TIMI MB

ITALIC N=3,700EES 6 vs. 12 mos A vs. A+C

NoninferiorityD/MI/CVA/

Urg Revasc/MB

OPTIMIZE N=3,120ZES 3 vs. 12 mos A vs. A+C

Noninferiority D/MI/CVA/MB

RESET‡ N=2,148E-ZES vs RZES, SES, EES 3 vs. 12 mos A+C vs. A+C CVD/MI/ST/

ID-TVR, Bleed*Plus a 3 month washout period‡Strategy not DAPT duration **2014-2015

Patients on current dual antiplatelet therapy without MACCE or major bleeding for at least the first 12 months after DES implantation (Total N~2,700)

Aspirin + clopidogrel Dual-therapy

(N=1,000)

Aspirin Mono-therapy(N=1,000)

1:1 randomization Stratified by (1) centers

(2) Initial DES types

Primary end points: The composite of cardiac death or MI

Regular Clinical assessment after randomization

Correlation of Clopidogrel Therapy Discontinuation in REAL-world Patients Treated with Drug-Eluting Stent Implantation and Late Coronary Arterial

Thrombotic Events:

REAL-LATE Trial

Fff

Fff

499 randomized to and received EES

502 randomized to and received BMS

500 randomized to and received ZES

498 randomized to and received PES

979 2 year follow-up

984 2 year follow-up

2,013 randomly allocated to recieve one of the four study stent types

1,970 DES and BMS randomized at 30

days

983

6 Months DAPT

987

24 Months DAPT

Valgimigli, M., et al., Circulation, 2012.

(1497 DES)

PRODIGY Study: 6 vs 24m DAPT after DES or BMS, randomized at 30 days

Not blinded

BMS 30d treatment allowed and counted as 6m

694 Excluded, 353 Not Meeting Inclusion Criteria232 Refused to Participate, 109 Operator’s choice

Primary EPDeath,MI,CVA

EXCELLENT Trial Design

Everolimus-Eluting StentN=1029

Sirolimus-Eluting StentN=343

Randomization3:1

1372 Patients Matching En-rollment Criteria

DAT 6 moN=515

DAT 12 moN=514

DAT 6 moN=171

DAT 12 moN=172

19 centers in Korea

1mo 3mo 9mo 12mo

Clinical

Angiographic

3yr2yr 4yr 5yr

clinical endpoint evaluation

Primary endpoint:In-segment LL

Percutaneous Coronary Intervention

Prospective, open label, two-arm, randomized multi-center trial

2x2 factorial design

Am Heart J 2009 May;157:811-817.e1.Gwon et al. Circ. 2012;125:505-513

7

TVF*

*CD,MI,IDTVR

OPTIMIZE STUDY

3,120 minimally selected* patients undergoing PCI with E-ZES in 33 sites in Brazil

Randomization ** (1:1)

Primary endpoint: Net Clinical Benefit † at 12-month FU

* Exclude ACS with + biomarker; prior DES Rx;SVG target** Stratified by DM and Institution; not blinded† composite endpoint of all-cause death, MI, CVA and major bleeding

DAPT for 3 months DAPT for 12 months N = 1,560 N= 1,560

Feres et al. AHJ 2012:164:810 e3Feres et al. TCT 2013 LBCT

Clinical FU at 1, 3, 6, 12 and 18 months and yearly up to 3 yrs

Ischemic Endpoints By DAPT Duration In Randomized Trials

Adapted from t Gwon et al. ACC 2011tt Valgimigli et al. ESC 2011ttt Park et al. NEJM 2010;362:1374tttt Feres et al. TCT 2013 LBCT

TVF* MACCE** D/MI D/MI/CVA D/MI D/MI/CVA Cardiac D/MI

MACE***0

2

4

6

8

10

12

4.7

8.4

9.6 10

1.7 1.8

4.6

8.4

4.4

7.5

8.9

10.1

2.33.2

4.1

7.5

% P

atie

nts

*Cardiac death / MI / TVR**Death / MI, CVA, Revasc***Death/MI/Revasc

EXCELLENT t PRODIGY tt REAL-LATE/ OPTIMIZE tttt ZEST-LATE ttt

6 mos (n=957) 6 mos (n=1546) 12 mos (n=1344) 3 mos (n=1563)12 mos (n=970) 24 mos (n=1500) 24 mos (n=1357) 12 mos (n=1556)

Major Bleeding (TIMI or GUSTO/REPLACE 2* ) By DAPT Duration In Randomized Trials

Adapted from t Gwon et al. ACC 2011tt Valgimigli et al. ESC 2011ttt Park et al. NEJM 2010;362:1374tttt Feres et al. TCT 2013 LBCT

0

0.5

1

1.5

2

2.5

3

0.3

0.6

0.1

0.70.6

1.6

0.2

0.8

% P

atie

nts

EXCELLENT t PRODIGY tt REAL-LATE/ OPTIMIZE tttt* ZEST-LATE ttt

6 mos 6 mos 12 mos 3 mos 12 mos 24 mos 24 mos 12 mos

P=0.42 P=0.04 P=0.35 P=0.66

Type II, III or V BARC Bleeding: PRODIGY

No. at Risk

24-month clopidogrel 987 925 884

6-month clopidogrel 983 919 881

Valgimigli et al. Circulation 2012; 125:2015-2026

0 180 360 540 7200

4

8

12 24 mo DAPT 6 mo DAPT

%

CEC adjudicated

Hazard ratio: 0.46 (0.1-0.69)

P=0.000187.4

3.5

PRODIGY BARC Bleeding Categories

Mehran et al. Circ 2011;123:2736-2747

BARC 2* BARC 3 BARC 50

2

4

6

8

10

4.0

2.5

0.91.5 1.4

0.5

24 mo DAPT 6 mo DAPT

%

*BARC 2 “Any overt, actionable sign of hemorrhage that…meets at least one of the following criteria: (1) requiring nonsurgical, medical intervention by a healthcare professional, (2) leading to hospitalization or increased level of care, or (3) prompting evaluation…no change in hemoglobin, blood transfusion or hemodynamic sequelae are required”

P=0.001

P=0.075

P=0.029

OPTIMIZE : NACCE at 1 Year(All-Cause Death, MI, Stroke, Major Bleeding)

No. at risk

3M DAPT 1563 1520 1504 1468 1384

12M DAPT 1556 1514 1497 1466 1381

Log-Rank P = 0.838

Cu

mu

lati

ve

In

cid

en

ce

o

f N

AC

CE

(%

)

Time After Initial Procedure (Months)

0 120

10

15

5

3 6 9

6.05.8

12M DAPT

3M DAPT

Feres et al. TCT 2013 LBCT

4.0 %-0.5 0.0 0.5 3.52.0 2.5 3.0-1.0

Zone of non-inferiorityPre-specified margin = 2.7%

1.0 1.5

Primary Non-Inferiority Endpoint Met

Non-inferiority P value

=0.002

Difference : 0.2% Upper 1-sided 95% CI : 2.0%

Non-inferior

Upper one-sided 95% CI

3M DAPT(N = 1563)

6.1%

3M DAPT(N = 1563)

6.1%

12M DAPT(N = 1556)

5.9%

Primary Endpoint: NACCE at 1 Year(All-Cause Death, MI, Stroke, Major Bleeding)

OPTIMIZE :Other Clinical Events at 1 Year*E

ve

nts

(%

)

*All P=NS

MACE MI Cardiac Death/MI

TLR Major Bleed0

2

4

6

8

10

12

8.4

3.2

4.6

3.5

0.7

7.5

2.8

4.13.2

0.8

3 Months DAPT (N = 1563) 12 Months DAPT (N = 1556)

14%

12%

12% 9.4%

12.5%

Ischemic / Efficacy Bleeding / Safety

Feres et al. TCT 2013 LBCT

OPTIMIZE: Stent Thrombosis* vs. Major Bleeding

ARC Def./Prob. Stent Thrombosis

3M DAPT12M DAPT

Time After Initial Procedure (months)

0.260.07

P = 0.18HR 3.97

(0.44-35.49)

0 120

10

5

3 6 9

P = 0.64HR 0.81

(0.34-1.96)

Cum

ulat

ive

Inci

denc

e (%

)

0.40.2

Cum

ulat

ive In

ciden

ce (

%)

P = 0.31HR 0.50

(0.12-1.99)

Time After Initial Procedure (months)0 12

0

10

5

3 6 9

P = 0.79HR 0.87

(0.32-2.40)

12M DAPT

3M DAPT

Major Bleeding

*0.2% absolute difference

~4x 2x

Feres et al. TCT 2013 LBCT

0.60.7

RESET2,148 patients enrolled and randomized

Divided into 4 subsets and 1:1 randomization was performed

31 patients excluded - 16 withdrawal of consent - 15 Met exclusion criteria

E-ZES with 3-month DAPT (N=1059) Standard therapy (N=1058)

Diabetes mellitusSubset (N=292)

Acute coronary syndromeSubset (N=601)

Short-length DESSubset (N=681)

Long-length DESSubset (N=543)

E-ZES(N=146)

R-ZES(N=146)

E-ZES(N=301)

R-ZES(N=300)

E-ZES (N=341)

SES(N=340)

E-ZES(N=271)

EES(N=272)

E-ZES with 3-month DAPT

Standard TherapyOther DES with 12-month DAPT

Kim et al. JACC 2012;60:1340-1348Primary Endpoint: CV death, MI, ST, ID-TVR, Bleed (TIMI major & minor)

RESET: Clinical Events Through 1 Year

4.7

0.8

0.2 0.2

4.7

1.3

0.30.6

0

1

2

3

4

5

CV Death, MI, ST,ID-TVR, Bleed*

Death, MI, ST Def/Prob ST** Major Bleed

E-ZES + 3 month DAPT (n=1,059) Standard Therapy (n=1,058)

% P

atie

nts

Adapted from Kim et al. JACC 2012 Sep 5 (e-Pub ahead of print)

*Primary Endpoint: (Assumed 10% with N.I. margin 4% for absolute difference in risk)**SORT OUT III / ENDEAVOR IV / PROTECT / KAMIR

40 41 8 11 2 3 2 6

ISAR-SAFEStudy Flowchart

1st FU: 1 month after randomization2nd FU: 6 months after randomization (at least one day after

study drug cessation)

3rd FU: 9 months after randomization (at least 3 months after study drug cessation)

Randomization

Continuous Clopidogrel therapy for 5 to 8 months

Placebofor 6 months

Clopidogrel 75 mg/dfor 6 months

Drug- Eluting Stenting

Follow Up

0

1st

9th

6th

- 8th to -5th

Primary

Analysis 2015

PEP = death,MI,stent thrombosis,stroke,TIMI major bleed

Study treatment period 12-30 mStudy observation period 30-33m

DAPT: Study Design

20

Eligible for Enrollment after PCI• Any PCI with DES or BMS• >18 years of age• No contradictions to dual antiplatelet therapy • Able and willing to provide written informed consent

Eligible for Randomization at 12 mStratified by DES v BMS, drug type, and

complexity (ACS or lesion-based)

Not Eligible for Randomization at 12 m

• Death• MI or repeat PCI at > 6 weeks• CABG• Stroke• Major Bleed

12 m DAPT Arm

Aspirin + blinded placebo

30 m DAPT Arm

Aspirin + blinded thienopyridine

Primary analysis DES treated subjects, 12-30m

Secondary analysis propensity matched BMS to DES subjects 0-30m

2 co-primary endpoints: stent thrombosis and MACCE (death, myocardial infarction or stroke)

Powered safety endpoint: major bleeding (GUSTO)

Total 33 month follow-upMauri, Kereiakes et al AHJ 2010;160:1038-1041

Total 33 month follow-up

18

mos

Primary

Analysis 2014

Thienopyridine Type: DAPT Study

68

32

Clopidogrel Prasugrel

All Randomized Subjects; N = 11,649

Stent Type: DAPT Study

86

14

DES BMS

All Randomized SubjectsN = 11,649

DES Type*

N = 9,961

Cypher (n=1,196) 12.0%

Endeavor (n=1,310) 13.1%

TAXUS (n=2,786) 28.0%

Xience/PROMUS (n=4,874) 48.9%

*Some patients received more than one DES type

Complexity Amongst Randomized Subjects: DAPT

*clinical =ACS, renal insufficiency LVEF <30%**anatomic=UPLM; >3 vessels; >2 lesions/vessel; LL ≥30mm; bifurcation; DES ISR; SVG; thrombus; VBT

Months after initial procedure

Cu

mu

lati

ve in

cid

ence

rat

e (%

)

Patient Number at Risks

6-month 722 707 701 697 681

12-month 721 710 699 698 680

P=0.507HR = 1.17 (95% CI 0.73-1.89)

4.7%

4.4%

6-mo DAT

12-mo DAT

Am Heart J 2009 May;157:811-817.e1.

EXCELLENT Trial:Target Vessel Failure

TVF According To Diabetes And DAPT Duration: EXCELLENT

Gwon et al,ACC 2011 LBCT

Patient Number at Risk6-mo 450 446 445 443 437

12-mo 443 435 432 429 416

p=0.022HR = 0.42 (95% CI 0.20-0.88)

p=0.005HR = 3.15 (95% CI 1.41-7.01)

2.2%

5.2%

8.8%

2.9%

Patient Number at Risk

272 261 259 255 245

278 275 271 270 265

Non-diabetics Diabetics 6-mo DAT

12-mo DAT

6 vs. 12 months DAPT After DES: EXCELLENT

Total 6 moDAPT n (%)

12 mo DAPT n (%)

HR (95% CI)P

valueInteraction P-value

Age <65 767 19 (5.1) 12 (3.2) 1.61 (0.78-3.31) 0.20 0.19 ≥65 676 15 (4.5) 18 (5.5) 0.83 (0.42-1.65) 0.59

ACS No 699 21 (6.03) 13 (3.82) 1.61 (0.8-3.21) 0.180.15

Yes 744 13 (3.65) 17 (4.69) 0.78 (0.38-1.60) 0.50

Diabetes No 893 10 (2.27) 22 (5.08) 0.44 (0.21-0.94) 0.03<0.001

Yes 550 24 (9.09) 8 (2.96) 3.16 (1.42-7.03) 0.005

LVEF ≥50% 1097 26 (4.91) 24 (4.42) 1.12 (0.64-1.95) 0.690.27

<50% 124 2 (3.08) 4 (7.41) 0.41 (0.07-2.23) 0.30

Stent type EES 1079 25 (4.72) 26 (4.94) 0.96 (0.55-1.66) 0.89 0.18

SES 364 9 (5.14) 4 (2.27) 2.31 (0.71-7.5) 0.16

Gwon et al. Circulation 2012;125:505-13

0.125 0.25 0.5 1 2 4 8Favors 6 mo DAPT Favors 12 mo DAPT

Clopidogrel Duration after PCI in Diabetics*: Death and Non-Fatal Myocardial Infarction

0

5

10

15

20

25

Brar et al. JACC 2008;51:2220

0 90 180 270 360 450 540 630 0 90 180 270 360 450 540 630 Time (days) Time (days)

# at risk < 6 mos 261 234 222 174 261 239 231 186 6- 9 mos 117 113 106 83 117 116 111 88 > 9 mos 371 358 356 286 371 362 361 293

Cum

ulat

ive

Inci

denc

e (%

)

< 6 months 6-9 months > 9 months

p <0.001 p < 0.001

0

5

10

15

20

25

Composite of death & MI Death

*749 consecutive diabetic patients/Kaiser L.A.

Stent Type and Clopidogrel Duration After PCI in Diabetics: Death and Non-Fatal Myocardial Infarction

0

5

10

15

20

Brar et al. JACC 2008;51:2220

0 90 180 270 360 450 540 630 0 90 180 270 360 450 540 630 Time (days) Time (days)

# at risk # at risk BMS with clop 147 145 139 DES with clop 323 312 220 BMS w/o clop 74 67 64 DES w/o clop 127 125 83

0

5

10

Cum

ulat

ive

Inci

denc

e (%

)

w/ clopidogrel w/ clopidogrel w/o clopidogrel w/o clopidogrel

BMSlandmark-left censored

P=0.01

DESlandmark-left censored

P=0.07

Multivariate Analysis Predictors of BARC Bleeding Events on DAPT*

OR (95% CI) P

Female 2.7 (1.8-4.1) <0.001

Non-diabetic 1.9 (1.2-3.1) 0.005

VLTPR (VASP≤10%) 4.7 (2.7-8.3) <0.001

-2 1 2 4 6 8 10

Adapted from Cuissett et al. JACC Card Int 2013;6:854-863

*1,542 patients (clopidogrel 1155; prasugrel 387)

Stent Thrombosis Stratified by Clinical Syndromeand Stent Type

0

1

2

3

4

5

0 6 12 18 24 30 36 0 6 12 18 24 30 36

Time (months) Time (months)

Kukreja et al. JACC Intv 2009;2:534

ACS vs SA logrank p<0.0001

ACS

SA

Def

inite

Ste

nt T

hrom

bosi

s (%

)

0

1

2

3

4

5

BMS: SA vs. ACS logrank p=0.01DES: SA vs. ACS logrank p=0.0007

SA: BMS vs. DES logrank p=0.2ACS: BMS vs. DES logrank p=0.06

DES, ACS

BMS, ACS

DES, SA

BMS, SA

N=5,816

Analysis of DAPT Duration Beyond 1 Year Following PCI for AMI*: COREA-AMI Registry

12-18 months 18-24 months >24 months0.0

5.0

10.0

15.0

20.0

25.0

18.0

10.28.9

% P

atie

nts

Deat

h, N

FMI,

Stro

ke

P<0.001 for trend

Koh et al. JACC 2013;61:A40 (abstract E161; presentation 1255M-178)

*2293 consecutive patients MACCE + major bleed free at 1 year post-MI

0

0.05

0.1

0.15

0.2

0 90 180 270 360 450 540 630 720

Follow-up time, days

*n=1455 (66% BMS, 34% DES) HR BMS 2.65; DES 2.0

Mortality Following PCI for ACS by Clopidogrel Use: Veterans Administration 2003-2004*

Ho et al. Am Heart J 2007;154:846

Cu

mu

lati

ve m

ort

alit

y ra

te

Off clopidogrel

On clopidogrel

Target And Non-target Lesion MACE* After StentingIn 1,057 Patients (Sirius Trial)

40

50

60

70

80

90

100

0 360 720 1080 1440 1880 0 360 720 1080 1440 1880 Time after Initial Procedure (days) Time after Initial Procedure (days)F

reed

om f

rom

Car

diac

Dea

th,

M I

and

Rev

asc

Target Vessel Non-target Vessel

*CV Death, M I, Revasc Chacko, Cutlip et al. JACC Intv 2009;2:498

% %

SESBMS

Log-Rank p<0.001

72.3%

57.1%

40

50

60

70

80

90

100

SESBMS Log-Rank p=0.096

74.3%

74.2%

CHARISMA: Dual Therapy Vs. ASA Monotherapy In Symptomatic* Patients

Bhatt et al. JACC 2007;49:1982-1988*Prior MI, CVA or symptomatic PAD

CD / MI / Stroke

Death / MI Events Following Clopidogrel Discontinuation After SVG PCI

Sachdeva et al. JACC 2012; Oct 25 [Epub ahead of print]

Failu

re ra

te

Failu

re ra

te

Cum

ulat

ive in

ciden

ce o

f D /

MI /

CVA

(%)

0 60 120 180 240 300 360 420 480 540 600 660 720

P=0.034

Time (days)

Campo et al. JACC 2013 prepub

Stenting for ISR: PRODIGY Substudy

0.85

0.90

0.95

1.00

short DAPT regimen (n=114) long DAPT regimen (n=110)

Definite Stent Thrombosis Through 3 Years In 18,334 Patients (28,739 Lesions) By Stent Type

0.0

0.5

1.0

1.5

2.0

2.5

3.0

0 1 2 3

Years after procedure

Sten

t thr

ombo

sis (%

)

Sten

t Thr

ombo

sis (%

)

3-Year Incidence of Stent Thrombosis 1-Year Landmark Analysis

BMS1G-DES2G-DES

Tada, Kastrati et al. JACC INTV 2013; 6:1267-74

0.0

0.5

1.0

1.5

2.0

2.5

3.0

0 1 2 3

Years after procedure

BMS1G-DES2G-DES

Clinical Outcomes By Statistical Model, Duration of DAPT And Follow-Up: Meta Analysis of 13 RCCT Involving 17,097 Patients

Stent Thrombosis TVR MI

Statistical Model Random (13) Fixed (13)Clopidogrel Duration 6 months (5) 12 months (7)Follow-up Duration ≤ 1 year (12) > 1 year (7)

Baber et al. JACC 2011;58:569-77

.1 1 10 0.4 4 0.4 4EES Non-EES EES Non-EES EES Non-EESFavors

Bangalore et al. Circ 2012;125:2873-91

Control Treatment Treatment Control Odds Ratio 95% CrI

BMS (Ref)

Sirolimus 0.80 0.61 1.10

Paclitaxel 1.11 0.85 1.49

Everolimus 0.46 0.31 0.70

Zotarolimus 0.69 0.39 1.28

Zotarolimus-R 0.62 0.29 1.44

Sirolimus (Ref)

Paclitaxel 1.38 1.02 1.84

Everolimus 0.57 0.39 0.84

Zotarolimus 0.87 0.48 1.50

Zotarolimus-R 0.78 0.35 1.73

Paclitaxel (Ref)

Everolimus 0.41 0.29 0.60

Zotarolimus 0.62 0.35 1.11

Zotarolimus-R 0.56 0.26 1.25

Everolimus (Ref)

Zotarolimus 1.52 0.77 2.83

Zotarolimus-R 1.36 0.68 2.71

Zotarolimus (Ref)

Zotarolimus-R 0.91 0.36 2.40

0.10 1.0 10.0* >86% probability that EES has lowest rate of “any” stent thrombosis

Long-term Risk Of Def/Prob Stent Thrombosis: Network Meta-Analysis Of 76 RCCT*

Network Meta-Analysis of 49 Trials Involving 50,844 Patients

Palmerini et al. Lancet 2012;379:1393-1402

Late definite or probable thrombosis ds rtio (95% CI)

CoCr-EES vs BMS 0.42 (0.17-0.95)

CoCr-EES vs PES 0.33 (0.15-0.71)

CoCr-EES vs R-ZES 0.24 (0.05-0.94)

CoCr-EES vs E-ZES 0.19 (0.04-0.75)

SES vs PES 0.41 (0.17-0.90)

PC-ZES vs SES 4.31 (1.08-19.05)

0.01 0.1 1 10 100

Favors stent 1 Favors stent 2

DAPT Duration: Conclusions

1. “One size shoe” approach for DAPT duration is unlikely to fit all patients• ACS• Diabetes• CABG-SVG / ISR

2. We treat symptomatic patients and non-target lesions with objective to reduce events (D/MI/CVA) which may not be stent (target lesion) related

3. Stent platforms differ with respect to risk for early , late and/or very late stent thrombosis events (“All DES not created equal”)

4. Conclusions regarding “optimal” DAPT duration should be based on adequately powered RCCT

45 ST events occurred in 44 pts with no DAPT interruption from day 1

through 2 yrs

40 ST events occurred in 39 pts with some DAPT interruption from day 1

though 2 yrs

17 events occurred “Off” DAPT

23 events occurred “On” DAPT

45 events occurred “On” DAPT*

Analysis population

11,219 / 13,259 (84.6%) pts complete DAPT data to 2 years

85 events in 83 pts (0.74%) through 2 years

Stent Thrombosis and DAPT Interruption Through 2 Years: Pooled Analysis of SPIRIT II-V; WOMEN; XV USA/India

►68/85 ST events (80.0%) occurred “On” DAPT

*One patient did not receive loading lose and was off DAPT at ST event (day 0) but started day 1 and never interrupted through 730 days.

Stone et al. JACC 2011;58(Suppl B):78