0. 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

1. 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

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

3. 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
Incidence of Stent Thrombosis
Iakovou, I, et al. JAMA. 2005;293:

4. BASKET LATE
Pfisterer et al. JACC 2006

5. Duke University PCI Registry
Eisenstein et al. JAMA 2007

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

7. 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:

8. 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

9. 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

10. 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:

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

12. 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
SE Rev A

14. Wide noninferiority margin

18. 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:

23. 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

24. 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

25. 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

26. 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

27. Thank you!
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