Dual anti platelet therapy duration where to draw the line

DES Introduction Stent Thrombosis Moses JW et al.. Stent Thrombosis Early Thienopyridine Discontinuation Iakovou I et al... Definite Stent Thrombosis Kyoto PCI/CABG Registry Tada T...

Dual Anti-Platelet Therapy Duration

Where to draw the line?

Marvin H Eng MD FSCAI FACC

Assistant Professor of Medicine

University of Texas Health Sciences Center San Antonio, TX

Disclosures

• No relevant disclosures

Leon MB et al NEJM 1998;339:1665-71

P=0.001

P=0.002

P=0.005

P=0.01

Clopidogrel in PCI

PCI-CURE

Mehta S et al Lancet 2001;358:527-33

DES Introduction

Stent Thrombosis

Moses JW et al NEJM 2003;349:1315-23

Stone GW et al Circulation2004;109:1942-7

Swiss DES Registry

BASKET-LATE

Pfisterer M et al JACC 2006;48:2584-91

DES BMS

Outcomes of Early Stent Thrombosis

Definite or Probable ST %

93.6 59.4 40.6 Unplanned

Stent Thrombosis

Early Thienopyridine Discontinuation

Iakovou I et al JAMA 2005;293:2126-2130

FDA Panel Analysis 2006

Laskey W et al Circulation 2007;115:2352

DAPT

ASA and Thienopyridine Stopping

Eisenberg MJ et al Circulation 2009;119:

DAPT Duration

Interruption vs Disruption

Mehran R et al Lancet 2013;382:1742-22

ADAPT-DES

Incidence of ST according to ACS

STEMI NSTEMI UA (no MI) No ACS P-value

Early (0-30d) 1.6% 0.57% 0.42% 0.22% <0.001 Late (31d-1yr) 0.25% 0.75% 0.48% 0.30% 0.14

V Late (>1yr) 0.25% 0.67% 0.43% 0.22% 0.11

Kirtane, AJ TCT 2014, Washington D.C

Definite Stent Thrombosis

Kyoto PCI/CABG Registry

Tada T et al Circulation Int 2012;5:381-91

DAPT

12 vs 24 months of DAPT (ZEST +REAL)

Park SJ et al NEJM 2010;362:1374-82

PRODIGY 6 month vs 24 months

Definite or probable ST at 24 months

Stent Thrombosis

Nakazawa G et al JACC 2011;57:390-8

1 st Generation Stents

Endothelialization

Nakazawa G et al JACC 2011;57:390-8

Stent Characteristics

Cypher Taxus Promus Endeavor Resolute Xience

Platform Bx Velocity Express/Li

berte

Element Driver Integrity ML Vision

Architecture Closed Open Open

Cobalt Chromium

Cobalt Chromium

VCF-HFP PC Biolinx VDF-HFP

Kinetics 80% in

30d

10.2%10d 80% 30d 98% 14 d 85% 60d 80% 30d

Elution Time 168 d Unknown 120 d 21-22 d 180 d 120 d

Adapted from Eng MH and Kandzari DE

E-ZES/EES

Neointimal Coverage

Kim SJ et al Coronary Artery Disease 2013; 24:431-439

DAPT Duration

RESET- 3 month DAPT in E-ZES

Kim BK et al JACC 2012;60:1340-8

Valgimigli, M et al AHJ 2013;166:831-8

Valgimigli, M et al ACC 2014, Washington D.C

1 month DAPT d/c 43.6%

2 month DAPT d/c 62.5%

> 6 months DAPT 24.7%

E-ZES

OCT by 2 week interval

Nishinari, M et al CCI 2013l82:E871-8

R-ZES Pooled Analysis

ST <30d vs 1-12 mo d/c

Silber S et al EHJ 2014;35:1949-56

EXCELLENT Stent thrombosis

6 month vs 12 month

Gwon HC et al Circulation 2012;125: 505-513

Risk for Recurrent Events

Related to Thrombotic Milieu

Stent Thrombosis

Pharmacology

PCI Technical Aspects

Thrombotic Substrate

Summary

• DAPT

– Clearly important for reducing early ST

– It is not clear that ST risk is reduced with ongoing DAPT

• Benefits may been associated with decreasing non-ST related events

• May have changed with newer generation stents

• May be dictated by patient inherent thrombotic risk

– 1 year still necessary for ACS patients

– 6 month minimum supported for STABLE CAD

• 3 months for DAPT

– E-ZES likely possible – CE mark for Xience but supporting data is not rigorous

Summary

• DAPT

– More potent agents may decrease ST

– Tailored therapy (no covered) has not proven to decrease thrombotic events

– Optimal duration and premature discontinuation still

unknown

• Understanding of late biological events

– Neoathetherosclerosis – Delayed stent healing – Understanding the body’s propensity to have thrombotic events

• Fertile research for biomarkers and stent design

– Bioabsorbable stents – Abluminal coating – Rapid endothelialization