ADAPT-DES Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents A Large-Scale,...

ADAPT-DESADAPT-DESAAssessment of ssessment of DDual ual AAntintiPPlatelet latelet TTherapy with herapy with DDrug-rug-EEluting luting SStentstents

A Large-Scale, Prospective, Multicenter Registry A Large-Scale, Prospective, Multicenter Registry

Examining the Relationship Between Platelet Examining the Relationship Between Platelet

Responsiveness and Stent Thrombosis Responsiveness and Stent Thrombosis

After DES Implantation After DES Implantation

Gregg W. Stone, MDGregg W. Stone, MDColumbia University Medical CenterColumbia University Medical Center

NewYork-Presbyterian HospitalNewYork-Presbyterian HospitalCardiovascular Research FoundationCardiovascular Research Foundation

Disclosure Statement of Financial Interest

• Consulting Fees/Honoraria • Abbott Vascular, Boston Scientific, Medtronic, Volcano, The Medicines Company, Daiichi Sankyo, Eli Lilly

Within the past 12 months, I or my spouse/partner have had a financial Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.interest/arrangement or affiliation with the organization(s) listed below.

Affiliation/Financial Relationship Company

• Although prior studies have shown a correlation between platelet hyporesponsiveness to ADP antagonists and stent thrombosis, all have been small to moderate in size. As such, several important questions remain unanswered:

What proportion of the risk of ST at different times after stent implantation can be attributed to platelet ADP antagonist response, and how useful is this to reclassify the risk of ST?

What is the optimal cutoff for platelet reactivity to predict stent thrombosis?

Is ADP antagonist hyporesponsiveness important in all pts? (e.g. non-diabetics as well as diabetics; stable CAD vs. ACS)

ADAPT-DES: Background I

ADAPT-DES: Background II

• Prior studies have emphasized the absolute level of platelet activation/aggregation to ADP antagonists

The role of the baseline level of platelet activation and % platelet inhibition to ADP antagonists have largely been unstudied

• The impact of

1) platelet hyporesponsiveness to aspirin, and

2) overall platelet aggregation on DAPT

on the risk of ST has been incompletely studied

ADAPT-DESADAPT-DESAAssessment of ssessment of DDual ual AAntintiPPlatelet latelet TTherapy with herapy with DDrug-rug-EEluting luting SStentstents

Up to 11,000 pts prospectively enrolledUp to 11,000 pts prospectively enrolledNo clinical or anatomic exclusion criteriaNo clinical or anatomic exclusion criteria

11 sites in US and Germany11 sites in US and Germany

Clinical FU at 30 days, 1 year and 2 yearsClinical FU at 30 days, 1 year and 2 yearsAngio core lab assessment all STs w/1:2 matching controlsAngio core lab assessment all STs w/1:2 matching controls

Assess platelet function after adequate DAPT loading and GPI washout: Accumetrics Assess platelet function after adequate DAPT loading and GPI washout: Accumetrics VerifyNow Aspirin, VerifyNow P2Y12, and VerifyNow IIb/IIIa assays (results blinded) VerifyNow Aspirin, VerifyNow P2Y12, and VerifyNow IIb/IIIa assays (results blinded)

PCI with ≥1 non-investigational DESPCI with ≥1 non-investigational DESSuccessful and uncomplicatedSuccessful and uncomplicated

(IVUS/VH substudy; Up to 3000 pts enrolled)(IVUS/VH substudy; Up to 3000 pts enrolled)

clinicaltrials.gov NCT00638794

ADAPT-DES: DAPT Loading and GPI Washout for DAPT Loading and GPI Washout for VerifyNow Assessment Post-PCIVerifyNow Assessment Post-PCI

• Aspirin loadingAspirin loading: : Pre-PCI mandatory: ≥300 mg non EC oral aspirin ≥6 hours prior to PCI or 324 mg chewed or ≥250 mg IV aspirin at least 30 minutes prior to PCI.

• Clopidogrel loadingClopidogrel loading: : Pre-PCI recommended, but in all cases Pre-PCI recommended, but in all cases 600 mg ≥6 hours or 300 mg ≥12 hours prior to VerifyNow, 600 mg ≥6 hours or 300 mg ≥12 hours prior to VerifyNow, or ≥75 mg for ≥5 days prior to VerifyNow.or ≥75 mg for ≥5 days prior to VerifyNow.

• GP IIb/IIIa inhibitor washoutGP IIb/IIIa inhibitor washout: : GP IIb/IIIa inhibitors may be GP IIb/IIIa inhibitors may be used per standard of care. If used, eptifibatide or tirofiban used per standard of care. If used, eptifibatide or tirofiban must have been discontinued for ≥24 hrs prior to VerifyNow, must have been discontinued for ≥24 hrs prior to VerifyNow, and abciximab must have been discontinued for ≥10 days and abciximab must have been discontinued for ≥10 days prior to VerifyNow.prior to VerifyNow.

ADAPT-DES: Study organizationPrincipal investigator:Principal investigator: Gregg W. Stone (Gregg W. Stone (&& Chuck Simonton prior to joining AVD) Chuck Simonton prior to joining AVD)

Co-principal investigators:Co-principal investigators: Thomas Stuckey, Bruce Brodie, Mike RinaldiThomas Stuckey, Bruce Brodie, Mike Rinaldi

Pharmacology committee:Pharmacology committee: Paul Gurbel and Steve SteinhublPaul Gurbel and Steve Steinhubl

Sponsor (IDE):Sponsor (IDE): Cardiovascular Research FoundationCardiovascular Research Foundation

Site management & monitoring:Site management & monitoring: R. Stuart Dickson Institute For Health Studies R. Stuart Dickson Institute For Health Studies Michael Dulin, director, Sherry Laurent, consultantMichael Dulin, director, Sherry Laurent, consultant

Data management:Data management: R. Stuart Dickson Institute For Health Studies R. Stuart Dickson Institute For Health Studies Susan Christopher, project leadSusan Christopher, project lead

Event adjudication:Event adjudication: Cardiovascular Research Foundation Cardiovascular Research Foundation Roxana Mehran and Ecaterina Cristea, directorsRoxana Mehran and Ecaterina Cristea, directors

Angio and IVUS core labs:Angio and IVUS core labs: Cardiovascular Research Foundation Cardiovascular Research Foundation Ecaterina Cristea and Akiko Maehara, directorsEcaterina Cristea and Akiko Maehara, directors

Biostatistics:Biostatistics: Cardiovascular Research Foundation Cardiovascular Research Foundation Helen Parise, directorHelen Parise, director

Financial support:Financial support: Boston Scientific, Abbott Vascular, Medtronic, Boston Scientific, Abbott Vascular, Medtronic, Cordis, Biosensors, The Medicines Company, Cordis, Biosensors, The Medicines Company, Daiichi-Sankyo, Eli Lilly, Volcano, AccumetricsDaiichi-Sankyo, Eli Lilly, Volcano, Accumetrics

ADAPT-DES: Sites and enrollment8,575 pts 8,575 pts werewere enrolled at 11 sites between 1/7/2008 and enrolled at 11 sites between 1/7/2008 and 9/16/2010; 9/16/2010; 2,158 pts 2,158 pts werewere enrolled in the IVUS substudyenrolled in the IVUS substudy

SiteSite Principal investigator(s)Principal investigator(s) N enrolledN enrolled

Charité Benjamin FranklinCharité Benjamin Franklin Bernhard WitzenbichlerBernhard Witzenbichler 1,4261,426

Columbia University Medical CenterColumbia University Medical Center Giora WeiszGiora Weisz 1,3691,369

Herz-Zentrum Bad KrozingenHerz-Zentrum Bad Krozingen Franz-Josef NeumannFranz-Josef Neumann 1,0351,035

Carolinas Medical CenterCarolinas Medical Center Mike RinaldiMike Rinaldi 1,1101,110

Wellmont Holstein ValleyWellmont Holstein Valley Chris MetzgerChris Metzger 790790

Minneapolis Heart InstituteMinneapolis Heart Institute Tim Henry and Ivan ChavezTim Henry and Ivan Chavez 788788

Lehigh Valley HospitalLehigh Valley Hospital David CoxDavid Cox 673673

Firsthealth Moore RegionalFirsthealth Moore Regional Peter DuffyPeter Duffy 544544

LeBauer CV ResearchLeBauer CV Research Bruce Brodie, Tom StuckeyBruce Brodie, Tom Stuckey 534534

Ohio State UniversityOhio State University Ernest MazzaferriErnest Mazzaferri 304304

Indiana Heart InstituteIndiana Heart Institute Jim HermillerJim Hermiller 22

ADAPT-DES: Baseline features (n=8,575)

Age (years) 63.6 ± 10.9 Female 25.9%Non-caucasian 11.4%Diabetes mellitus 32.4% - Insulin-treated 11.6%Hypertension 79.6%Hyperlipidemia 74.4%Cigarette smoking, current 22.6%Prior MI 25.2%Prior PCI 42.8%Prior CABG 17.1%Prior CHF 8.1% Prior PAD 10.2%History of renal insufficiency 7.7% - Dialysis 1.6%BMI 29.5 ± 5.7

Presentation during PCI - Stable CAD 48.3% - ACS 51.7% - UA, biomarker negative 27.7% - NSTEMI 14.5% - STEMI 9.5% Extent of CAD - 1 vessel disease 38.3% - 2 vessel disease 33.0% - 3 vessel disease 28.7% - Left main disease 3.0%LVEF (%) 55.0 ± 14.1LVEDP (mmHg) 16.7 ± 9.3

ADAPT-DES: Baseline features (n=8,575)

ADAPT-DES: Anti-platelet agents (n=8,575)

Aspirin

- Pre-admission 82.0%

- Loading dose pre-PCI 88.7%

- Discharge 99.2%

Thienopyridine

- Pre-admission 42.8%

- Loading dose pre-PCI 86.4%

- Discharge 99.7%

• Ticlopidine n=3 (0.04%)

• Clopidogrel n=8,541 (99.7%)

• Prasugrel n=26 (0.3%)

ADAPT-DES: PCI procedure (n=8,575)

N vessels treated per pt 1.2 ± 0.4 - LM 3.7% - LAD 46.0% - LCX 30.9% - RCA 37.0% - bypass graft 3.3%N lesions treated per pt 1.8 ± 1.1 N stents per pt 1.7 ± 1.0Total stent length (mm) 32.4 ± 22.3 DES type used per pt / lesion - Xience V / Promus 64.4% / 58.3% - Taxus (Express, Liberté) 16.5% / 14.4% - Cypher 13.5% / 13.0% - Endeavor 6.2% / 5.2% - Resolute 2.2% / 2.1% - Other 0.2% / 0.2%

N = 10,091 vessels, 12,898 lesions

ADAPT-DES: Platelet function test results (n=8,575)

Post-PCI to VerifyNow (hrs) 19.0 [16.3, 21.8]

VerifyNow Aspirin (ARU) 419 ± 55

- ≥ 550 ARU* 5.6%

VerifyNow P2Y12 (BASE) 310 ± 58

VerifyNow P2Y12 (PRU) 188 ± 97

- > 208 PRU* 42.7%

- ≥ 230 PRU* 35.0%

VerifyNow P2Y12 Inhibition (%) 40.0 ± 28.3

VerifyNow IIb/IIIa PAU 193 ± 53

*Pre-specified cut-off values*Pre-specified cut-off values

ADAPT-DES: Stent Thrombosis Within 30 Days

Definite or probable 0.46% (39) - Definite 0.32% (27) - Probable 0.14% (12)

Days to definite or probable stent thrombosisDays to definite or probable stent thrombosis

Stent thrombosis (ARC def/prob) occurred in 39 (0.46%) ptsStent thrombosis (ARC def/prob) occurred in 39 (0.46%) pts

Probable

Fre

qu

ency

0

1

2

3

4

5

6

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30

Definite

Rates are KM estimates (n).Rates are KM estimates (n).

VerifyNow test Def/prob ST No def/prob ST P(n=39) (n=8536)

Aspirin ARU 425.6 ± 60.1 419.2 ± 55.3 0.46

- ARU ≥550 7.7% 5.6% 0.57

P2Y12 Base 301.7 ± 63.9 309.6 ± 58.1 0.41

P2Y12 PRU 249.4 ± 88.5 187.6 ± 96.7 0.0001

- PRU >208 74.4% 42.6% 0.0002

- PRU ≥230 64.1% 34.9% 0.0003

P2Y12 % Inhibition 19.8 ± 23.7 40.1 ± 28.2

<0.0001

- Inhibition ≤11% 51.3% 19.9%

<0.0001

IIb/IIIa PAU 188.2 ± 54.9 192.7 ± 53.4 0.60

ADAPT-DES: Relationship between VerifyNow platelet response to DAPT and subsequent

definite or probable stent thrombosis

VerifyNow test Def/prob ST Definite ST

AUC Cut-off AUC Cut-off

Aspirin ARU 0.563 403 0.626 403

P2Y12 Base 0.536 289 0.604 303

P2Y12 PRU 0.679 206 0.716 230

P2Y12 % Inhibition 0.720 25% 0.787 11%

IIb/IIIa PAU 0.542 195 0.587 181

ADAPT-DES: ROC curve analysis of the relationship between VerifyNow assessed platelet response to

DAPT and subsequent stent thrombosis

ADAPT-DES: Relationship Between VerifyNow P2Y12 PRU and Stent Thrombosis within 30 Days

Definite or probable stent thrombosisDefinite or probable stent thrombosisD

efin

ite/

Pro

bab

le S

T (

%)

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

DaysDays0 5 10 15 20 25 30

16911691 16651665 16631663 1640164016881688 16571657 16571657 1630163017051705 16771677 16761676 1656165616661666 16331633 16311631 1607160716911691 16621662 16591659 16351635

Number at RiskNumber at RiskQuintile 1Quintile 1Quintile 2Quintile 2Quintile 3Quintile 3Quintile 4Quintile 4Quintile 5Quintile 5

0.18% 0.24% 0.36%

0.79% 0.78%

P2Y12 PRU Q1 (≤94) (n=1691)P2Y12 PRU Q2 (95-160) (n=1701)P2Y12 PRU Q3 (161-216) (n=1705)P2Y12 PRU Q4 (217-275) (n=1666)P2Y12 PRU Q5 (≥276) (n=1691)

ADAPT-DES: Relationship Between VerifyNow P2Y12 PRU and Stent Thrombosis within 30 Days


efin

ite/

Pro

bab

le S

T (

%)

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

Days0 5 10 15 20 25 30

36073607 35403540 35343534 3482348248344834 47544754 47524752 46864686

Number at riskNumber at risk

>208 PRU>208 PRU≤≤208 PRU208 PRU

0.81%0.81%

0.21%0.21%

P2Y12 PRU > 208 (n=3607)

P2Y12 PRU ≤ 208 (n=4834)

P <0.001

HR [95% CI]=3.89 [1.90, 7.98]

ADAPT-DES: Relationship Between VerifyNow P2Y12 % Inhibition and Stent Thrombosis within 30 Days


efi

nit

e/P

rob

ab

le S

T (

%)

De

fin

ite

/Pro

ba

ble

ST

(%

)

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

DaysDays0 5 10 15 20 25 30

1694 1667 1663 16371672 1647 1647 16271676 1641 1639 16131744 1712 1712 16921653 1626 1624 1598

Number at RiskQuintile 1Quintile 2Quintile 3Quintile 4Quintile 5

1.19%

0.42% 0.42%

0.17% 0.12%

P2Y12 % Q1 (≤11) (n=1694)P2Y12 % Q1 (≤11) (n=1694)P2Y12 % Q2 (12-28) (n=1672)P2Y12 % Q2 (12-28) (n=1672)P2Y12 % Q3 (29-46) (n=1676)P2Y12 % Q3 (29-46) (n=1676)P2Y12 % Q4 (47-68) (n=1744)P2Y12 % Q4 (47-68) (n=1744)P2Y12 % Q5 (≥69) (n=1626)P2Y12 % Q5 (≥69) (n=1626)

ADAPT-DES: Relationship Between VerifyNow P2Y12 % Inhibition and Stent Thrombosis within 30 Days


efi

nit

e/P

rob

ab

le S

T (

%)

De

fin

ite

/Pro

ba

ble

ST

(%

)

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

DaysDays0 5 10 15 20 25 30

1694 1667 1663 16376745 6626 6622 6530

Number at risk≤11%>11%

1.19%

0.29%

VerifyNow P2Y12 % Lowest Quintile (≤11) (n=1694)VerifyNow P2Y12 % Highest 4 Quintiles (>11) (n=6745)

P<0.001

HR [95% CI]=4.18 [2.23, 7.82]

ADAPT-DES: Multivariable (Cox PHR) models of 30-day stent thrombosis stratified by propensity quintiles

VerifyNow test N N Adj. HR* P AttributableAttributableP2Y12 at risk events [95%CI] value events percent

P2Y12 PRU >208† 8439 39 3.00 0.005 19.3 49.6%[1.39, 6.49] [8.1, 24.5] [20.7%,

62.9%]

P2Y12 PRU ≥230† 8439 39 2.75 0.005 15.9 40.8%[1.35, 5.60] [6.4, 20.5] [16.5%,

52.7%]

Inhibition ≤11%† 8437 39 2.78 0.003 12.8 32.8%[1.43, 5.40] [6.0, 16.3] [15.4%,

41.8%]

Definite or probable stent thrombosisDefinite or probable stent thrombosis

††Pre-specified measuresPre-specified measures

*Adjusted for non-ACS vs NSTEMI vs STEMI, diabetes vs no diabetes, and stent length*Adjusted for non-ACS vs NSTEMI vs STEMI, diabetes vs no diabetes, and stent lengthModel c-statistics = 0.609, 0.591, 0.623Model c-statistics = 0.609, 0.591, 0.623


VerifyNow test N N HR P AttributableAttributable

at risk events [95%CI] value events percent

P2Y12 PRU >208 8439 39 3.00 0.005 19.3 49.6%[1.39, 6.49] [8.1, 24.5] [20.7%,

62.9%]

P2Y12 PRU ≥230 8439 39 2.75 0.005 15.9 40.8%[1.35, 5.60] [6.4, 20.5] [16.5%,

52.7%]

Inhibition ≤11% 8437 39 2.78 0.003 12.8 32.8%[1.43, 5.40] [6.0, 16.3] [15.4%,

41.8%]

ARU ≥550 8517 39 1.69 0.39 1.2 3.1%[0.51, 5.61] [-2.9, 2.5] [-7.4%, 6.3%]

P2Y12 Base ≥360 8436 39 1.18 0.70 1.4 3.6%[0.50, 2.80] [-9.0, 5.8] [-23.0%,

14.8%]

GPIIb/IIIa ≥238 8265 38 0.66 0.37 -3.1 -8.1%[0.27, 1.64] [-16.5, 2.3] [-43.5%,

6.1%]

Definite or probable stent thrombosisDefinite or probable stent thrombosis



P2Y12 PRU >208† † 8439 27 5.36 0.002 17.9 66.3%[1.89, 15.21] [10.4, 20.6] [38.3%,

76.1%]

P2Y12 PRU ≥230† † 8439 27 4.46 0.001 14.7 54.6%[1.80, 11.03] [8.5, 17.3] [31.4%,

64.0%]

Inhibition ≤11%† † 8437 27 4.60 0.0003 13.3 49.3%[2.01, 10.55] [8.5, 15.4] [31.6%,

57.0%]

Definite stent thrombosisDefinite stent thrombosis


*Adjusted for non-ACS vs NSTEMI vs STEMI, diabetes vs no diabetes, and stent length*Adjusted for non-ACS vs NSTEMI vs STEMI, diabetes vs no diabetes, and stent lengthModel c-statistics = 0.753, 0.721, 0.722Model c-statistics = 0.753, 0.721, 0.722


VerifyNow test N N HR P AttributableAttributable

at risk events [95%CI] value events percent

P2Y12 PRU >208 8439 27 5.36 0.002 17.9 66.3%[1.89, 15.21] [10.4, 20.6] [38.3%,

76.1%]

P2Y12 PRU ≥230 8439 27 4.46 0.001 14.7 54.6%[1.80, 11.03] [8.5, 17.3] [31.4%,

64.0%]

Inhibition ≤11% 8437 27 4.60 0.0003 13.3 49.3%[2.01, 10.55] [8.5, 15.4] [31.6%,

57.0%]

ARU ≥550 8517 27 2.87 0.09 2.0 7.2%[0.84, 9.82] [-0.6, 2.7] [-2.1%,

10.0%]

P2Y12 Base ≥360 8436 27 0.99 0.99 0.0 -0.1%[0.33, 2.99] [-10.2, 3.3] [-37.7%,

12.3%]

GPIIb/IIIa ≥238 8265 27 0.43 0.18 -3.9 -14.5%[0.13, 1.49] [-20.8, 1.0] [-77.0%,

3.7%]

Definite stent thrombosisDefinite stent thrombosis

ADAPT-DES: ADAPT-DES: Predictive accuracy of VerifyNow testing – all pts (n=8,575)

VerifyNow test Sensitivity Specificity PPV NPV AccuracyASA ARU > 550 7.7% 94.4% 0.6% 99.6% 94.0%

P2Y12 PRU > 208 74.4% 57.4% 0.8% 99.8% 57.5%

P2Y12 PRU ≥ 230 64.1% 65.1% 0.8% 99.7% 65.1%

P2Y12 % Inhibition ≤ 11% 51.3% 80.1% 1.2% 99.7% 79.9%

IIb/IIIa PAU ≥ 238 15.8% 80.2% 0.4% 99.5% 79.9%

Definite or probable stent thrombosis by 30 days (n=39)Definite or probable stent thrombosis by 30 days (n=39)

VerifyNow test Sensitivity Specificity PPV NPV AccuracyASA ARU > 550 11.1% 94.4% 0.6% 99.7% 94.1%

P2Y12 PRU > 208 81.5% 57.4% 0.6% 99.9% 57.5%

P2Y12 PRU ≥ 230 70.4% 65.1% 0.6% 99.9% 65.1%

P2Y12 % Inhibition ≤ 11% 63.0% 80.1% 1.0% 99.9% 80.0%

IIb/IIIa PAU ≥ 238 11.1% 80.1% 0.2% 99.6% 79.9%

Definite stent thrombosis by 30 days (n=27)Definite stent thrombosis by 30 days (n=27)

ADAPT-DES: ADAPT-DES: ADP Platelet Responsiveness in Pts ADP Platelet Responsiveness in Pts with and without Definite/Probable Stent with and without Definite/Probable Stent

Thrombosis within 30 DaysThrombosis within 30 Days

Median [IQR]Median [IQR]188 [112, 260]188 [112, 260]


P=0.0001P=0.0001

N=8402N=8402 N=39N=39No Stent ThrombosisNo Stent Thrombosis Stent ThrombosisStent Thrombosis

00

100100

200200

300300

400400

500500

600600

Ver

ifyN

ow

P2Y

12 (

PR

U)

Ver

ifyN

ow

P2Y

12 (

PR

U)

N=8400N=8400 N=39N=39No Stent ThrombosisNo Stent Thrombosis Stent ThrombosisStent Thrombosis

00


P<0.0001P<0.0001


2525

5050

7575

100100

Ver

ifyN

ow

P2Y

12 P

ER

CE

NT

(%

)V

erif

yNo

w P

2Y12

PE

RC

EN

T (

%)

ADAPT-DES: ADAPT-DES: Relationship between ACS and Relationship between ACS and stent thrombosisstent thrombosis

P=0.002P=0.002

9/4140 30/4435 10/2377 7/1246 13/812

ADAPT-DES: Relationship between ACS and VerifyNow response to DAPT

VerifyNow test ACS No ACS P(n=4435) (n=4140)

Aspirin ARU 419.5 ± 54.4 419.0 ± 56.4 0.66

- ARU ≥550 5.4% 5.8% 0.43

P2Y12 Base 304.6 ± 57.6 314.8 ± 58.1 <0.0001

P2Y12 PRU 193.8 ± 96.2 181.7 ± 97.0 <0.0001

- PRU >208 45.6% 39.7% <0.0001

- PRU ≥230 37.6% 32.3% <0.0001

P2Y12 % Inhibition 37.3 ± 28.2 42.9 ± 28.1 <0.0001

- Inhibition ≤11% 23.3% 16.6% <0.0001

IIb/IIIa PAU 187.9 ± 52.3 197.8 ± 54.1 <0.0001



PRU >208† † 4347 30 3.91 0.005 17.9 59.5%[1.51, 10.11] [8.1, 21.6] [27.0%,

72.1%]

PRU ≥230† † 4347 30 2.95 0.01 13.2 44.1%[1.29, 6.77] [4.5, 17.0] [14.9%,

56.8%]

Inhibition ≤11%† † 4346 30 3.53 0.001 12.2 40.6%[1.66, 7.52] [6.8, 14.7] [22.6%,

49.1%]

ACS: ACS: Definite or probable stent thrombosisDefinite or probable stent thrombosis


*Adjusted for diabetes vs no diabetes and stent length*Adjusted for diabetes vs no diabetes and stent lengthModel c-statistics = 0.541, 0.464, 0.524Model c-statistics = 0.541, 0.464, 0.524



PRU >208† † 4092 9 1.49 0.59 1.6 18.3%[0.35, 6.36] [-9.3, 4.2] [-103.0%,

46.8%]

PRU ≥230† † 4092 9 2.02 0.35 2.5 28.0%[0.46, 8.74] [-5.8, 4.4] [-64.0%,

49.2%]

Inhibition ≤11%† † 4091 9 2.22 0.28 1.6 18.3%[0.53, 9.28] [-2.7, 2.7] [-29.6%,

29.7%]

No ACS: No ACS: Definite or probable stent thrombosisDefinite or probable stent thrombosis


*Adjusted for diabetes vs no diabetes and stent length*Adjusted for diabetes vs no diabetes and stent lengthModel c-statistics = 0.704, 0.705, 0.760Model c-statistics = 0.704, 0.705, 0.760

ADAPT-DES: Conclusions and ImplicationsConclusions and Implications

• The absolute and relative levels of platelet inhibition The absolute and relative levels of platelet inhibition to ADP antagonists as assessed by the VerifyNow to ADP antagonists as assessed by the VerifyNow P2Y12 test are powerful independent predictors of P2Y12 test are powerful independent predictors of stent thrombosis within 30 days, with a stent thrombosis within 30 days, with a significant significant proportion of events independently attributable to proportion of events independently attributable to clopidogrel hyporesponsiveness.clopidogrel hyporesponsiveness.

• In contrast, the Base level of platelet P2Y12 In contrast, the Base level of platelet P2Y12 response, as well as aspirin and overall platelet response, as well as aspirin and overall platelet responsiveness after DAPT loading as assessed by responsiveness after DAPT loading as assessed by VerifyNow VerifyNow were not shown to be relatedwere not shown to be related to the 30- to the 30-day rate of stent thrombosis.day rate of stent thrombosis.


• These data suggest that agents which more effectively These data suggest that agents which more effectively inhibit ADP-induced platelet activation should reduce inhibit ADP-induced platelet activation should reduce 30-day stent thrombosis 30-day stent thrombosis when applied to large patient when applied to large patient populationspopulations (underlying the positive findings of (underlying the positive findings of TRITON-TIMI 38 and PLATO).TRITON-TIMI 38 and PLATO).

• However, the modest sensitivity and specificity of However, the modest sensitivity and specificity of platelet function testing, coupled with the low platelet function testing, coupled with the low prevalence of events, implies that testing of platelet prevalence of events, implies that testing of platelet ADP antagonist responsiveness is unlikely to provide ADP antagonist responsiveness is unlikely to provide useful information to guide clinical decision-making useful information to guide clinical decision-making in most individual patients for the prevention of stent in most individual patients for the prevention of stent thrombosis at 30 days.thrombosis at 30 days.

• The degree of platelet responsiveness to ADP The degree of platelet responsiveness to ADP antagonist loading is useful to predict 30-day stent antagonist loading is useful to predict 30-day stent thrombosis in diabetic and non-diabetic patients, as well thrombosis in diabetic and non-diabetic patients, as well as those with ACS, but as those with ACS, but may have less clinical utility in may have less clinical utility in patients with stable CAD. patients with stable CAD.

• The very low stent thrombosis rate in pts with stable The very low stent thrombosis rate in pts with stable CAD, coupled with the poor prognostic utility of platelet CAD, coupled with the poor prognostic utility of platelet function testing in this setting suggests that assessing function testing in this setting suggests that assessing DAPT response in pts without ACS undergoing PCI is DAPT response in pts without ACS undergoing PCI is unlikely to provide incremental clinical utility, unlikely to provide incremental clinical utility, and may and may explain the negative results of trials such as GRAVITAS explain the negative results of trials such as GRAVITAS and TRIGGER-PCI. and TRIGGER-PCI.


• The relationship between platelet responsiveness The relationship between platelet responsiveness testing and the occurrence of late and very late testing and the occurrence of late and very late stent thrombosis (in patients who have maintained stent thrombosis (in patients who have maintained and discontinued DAPT) will be assessed during and discontinued DAPT) will be assessed during the the 2-year clinical follow-up phase 2-year clinical follow-up phase of the ADAPT-of the ADAPT-DES study. DES study.


ADAPT-DES Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents A Large-Scale,...

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