Stent Thrombosis and the Optimal Duration of Dual Anti-platelet Therapy Kirk N Garratt MSc MD FSCAI Society for Cardiac Angiography and Interventions Lenox Hill Heart and Vascular Institute of New York

Disclosures Speaker’s bureau: Research support: Consulting: Equity DSI/Lilly Consulting: Boston Scientific The Medicines Company Research support: Abbott Vascular Boston Scientific The Medicines Company CardiacAssist Equity Infarct Reduction Technologies Guided Delivery Systems MedLogics

Current Controversies In DAPT After DES Which drug? When to start? Which dose? How long?

Correlates of Stent Thrombosis Univariate Correlates of Cumulative Stent Thrombosis Premature Antiplatelet Therapy Discontinuation Prior Brachytherapy Renal Failure Bifurcation with 2 Stents Bifurcation Lesion Unprotected Left Main Artery Diabetes Hazard Ratio for APT Discontinuation 89 0 10 20 30 40 Incidence of Stent Thrombosis Iakovou, I, et al. JAMA. 2005;293:2126-30

BASKET LATE Pfisterer et al. JACC 2006

Duke University PCI Registry Eisenstein et al. JAMA 2007

Why Does Thrombosis Happen? Thrombosis Risk Lesion Factors Patient Factors Product Factors Extraneous Factors

Rebound Following Clopidogrel Withdrawal Risk-Adjusted Instantaneous Incidence Rates of Death or AMI Over Time After Stopping Treatment With Clopidogrel Among Medically Treated and PCI-Treated Patients With ACS Using Multivariable Cox Regression Models Ho PM, et al. JAMA. 2008;10;299:532-539

Postprocedural Antiplatelet Therapy 2011 ACCF/AHA/SCAI Guideline for PCI Postprocedural Antiplatelet Therapy I IIa IIb III A After PCI, aspirin should be continued indefinitely. The duration of P2Y12 inhibitor therapy after stent implantation should generally be as follows: In patients receiving a stent (BMS or DES) during PCI for ACS, P2Y12 inhibitor therapy should be given for at least 12 months (clopidogrel 75 mg daily); prasugrel 10 mg daily; and ticagrelor 90 mg twice daily. In patients receiving a DES for a non–ACS indication, clopidogrel 75 mg daily should be given for at least 12 months if patients are not at high risk of bleeding. In patients receiving a BMS for a non-ACS indication, clopidogrel should be given for a minimum of 1 month and ideally up to 12 months (unless the patient is at increased risk of bleeding; then it should be given for a minimum of 2 weeks). I IIa IIb III DES recipients should receive DAPT for at least 12 months B 8

2011 ACCF/AHA/SCAI Guideline for PCI Postprocedural Antiplatelet Therapy I IIa IIb III Continuation of clopidogrel, prasugrel or ticagrelor beyond 12 months may be considered in patients undergoing DES placement. 9

Patients on double antiplatelet therapy (%) Is Prolonged DAPT Definitively Correlated With Reduced Ischemic Events? 100 20 40 60 80 1 2 3 4 5 Thrombosis rate (%) Patients on double antiplatelet therapy (%) 30 d 180 d 360 d 540 d 97.6 80.7 42.8 23.2 4.2 0.9 0.8 0.3 0.2 0.4 0.1 Thrombosis rate without thienopyridine Thrombosis rate with thienopyridine Airoldi F, et al. Circulation. 2007;116:745-754

Cumulative Stent Thrombosis According to DAPT Interruption ARC definite or probable stent thrombosis DAPT D/C at: 1-6 mo 6-12 mo 12-24 mo Never Kedhi et al, ACC 2012

Stent Thrombosis Definite/Probable ARC (%) Two-year Cumulative Stent Thrombosis: Landmark Analysis Beyond 6 Months discontinuation at 24 m No DAPT DAPT discontinuation 12-24 m 6-12 m 2.5 1.5 0·3 0·4 1·2 1·7 0·5 p for trend = 0·97 p for trend = 0·04 p = 0·51 p = 0·17 p = 0·82 p = 0·89 p = 0·01 Stent Thrombosis Definite/Probable ARC (%) p = 0·86 1 2 EES PES SE2936486 Rev A

Wide noninferiority margin

PRODIGY Study Design R 6 months vs 24 months Short-term of DAPT 1,970 patients with BMS, ZES, PES, EES (1:1:1:1) 30 days of DAPT R Short-term of DAPT 6 months* Long-term of DAPT 24 months 24 months of follow up after randomization Primary Endpoint: Composite of death, myocardial infarction, cerebrovascular accidents *<6 months clopidogrel was allowed in BMS pts with stable CAD at the time of PCI Valgimigli M et al, Circulation 2012;125:2015-26

Dual Antiplatelet Therapy Study 12 mo 18 mo DES n=15,245 BMS n=5,400 All patients on aspirin + open-label thienopyridine therapy for 12 months 50% of patients continue on dual antiplatelet therapy (clopidogrel or prasugrel) 50% of patients receive aspirin + placebo 1:1 Randomization at month 12 Total 33-month patient evaluation including additional 3-month follow-up 23

Assess ischemic event risk Assess bleeding risk Index procedure DES placed Low High What To Do? Assess other risks* DAPT for 12 months DAPT for 6 months DAPT for >24 months DAPT for 12 months DAPT for 6 months DAPT for 6 months DAPT for 12 months DAPT for 6 months Strongly support shorter therapy Weakly support shorter therapy Strongly support longer therapy Weakly support longer therapy *Prior CVA (Class III stroke guidelines), economic constraints, intolerable nuisance bleeding

Stent Thrombosis and DAPT Many factors influence incidence rates of stent thrombosis following DES Some uncontrollable Some likely unknown Some randomized trial data available to guide decision making Limited Overall suggests little value in prolonging DAPT beyond 6 months

Stent Thrombosis and DAPT Guidelines urge 12 months, perhaps more Current RCT data not conclusive Guidelines are fluid Do what you feel is best for the patient Assess likely risk Assess likely benefit

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