The document presents an overview of stent thrombosis and in-stent restenosis associated with drug-eluting stents (DES), highlighting complications like stent thrombosis, its definitions, classifications, and mechanisms. It emphasizes the significance of dual-antiplatelet therapy (DAPT) and discusses risks related to noncardiac surgery post-percutaneous coronary intervention. Key recommendations include managing DAPT in relation to surgical interventions based on bleeding risk and stent history.

1. Problem associated with Drug eluting stent
Presenter
Dr PRAVEEN GUPTA
Moderator
Dr. Ajith Ananthakrishna
Pillai
Date
16/09/2016
Departement of Cardiology,
JIPMER,
Pondicherry (India)
1

2. Stent thrombosis
Introduction
 Most feared complication
 with low-pressure inflation
and single-antiplatelet
therapy, 20% ST
 Dual-antiplatelet therapy
(DAPT) ,adequate stent
expansion using high-
pressure balloon inflation
achieved 1.6% rate of ST
at 6-month follow-up
 Up to 1 year follow-up for
DES - 0.6% to 3.2%
2

3. Stent thrombosis
Introduction
• very late ST may occur steadily at an annual rate of 0.4% to
0.6% after first-generation DES implantation
3

4. Definition and classification
4

5. 5

6. 6

7. Clinical Presentation,
 Chest pain
 Ischemic electrocardiographic changes in the target
vessel territory.
 Sudden death,
 It can be asymptomatic in the setting of collateral
vessels.
7

8. Angiographic characteristics of definite stent thrombosis: role
of thrombus grade, collaterals, epicardial coronary flow, and
myocardial perfusion.
8
The majority of ST patients present with late/very late ST with high
thrombus burden and STEMI. Presence of collateral vessels and low
thrombus burden is cardioprotective, while reduced initial TIMI flow is
associated with larger infarct size and recurrent ST.

9. Diagnosis
 Angiographic detection of thrombus is the presence of a filling
defect.
 intravascular ultrasound (IVUS) For underlying mechanism
responsible for stent thrombosis
 optical coherence tomography (OCT)
9

10. Mechanisms
 DES induce platelet adhesion, activation and thrombus
formation
 Cytotoxic drugs-inhibit endothelialisation .
 Sirolimus & paclitaxel -activation of the coagulation system.
 The polymers -hypersensitivity reaction / prothrombotic
environment
10

11. Mechanisms
 Persistent slow coronary blood flow and low shear stress
leading to activation of the intrinsic pathway;
 Premature discontinuation of DAPT
 Systemic prothrombotic state (e.g., due to ACS or
malignancy).
• Most consistently reported predictors are early DAPT
discontinuation, the extent of coronary artery disease, and
total stent length
11

12. Early ST
 technical and procedural
factors are important.
 A suboptimal procedural
result
 slow flow,
 inadequate post-procedural
lumen dimensions,
 residual dissection,
 tissue prolapse
 discontinuation of
DAPT
 Stenting in
prothrombotic
conditions in patients
with ACS/malignancy
12

13. Late and very late ST
 Delayed endothelial coverage, persistent fibrin deposition, &
ongoing vessel inflammation
 DES compared with BMS
 Late stent malapposition more commonly in DES compared
with BMS
 neoatherosclerotic plaques - rupture, causing ST
13

14. In-stent Restenosis
Introduction
 gradual re-narrowing of the
stented segment occurs mostly
between 3 to 12 months after
stent placement.
 DES -restenosis rates 0%- 16%
 target vessel revascularization
(TVR), 5% to 10
 Presents as recurrent angina,
but can present as acute
myocardial infarction in
approximately 10 percent of
patients.
14

15. Definition
 Angiographic” restenosis means recurrent diameter stenosis
(late lumen loss – LLL) >50% within the stent segment or its
edges (5 mm segments adjacent to the stent) in follow-up
 “Clinical” restenosis, symptoms or ischemia recurrence with
>50% diameter stenosis or >70% diameter stenosis without
symptoms
15

16. 16

17. Morphological classification of ISR
Mehran system,
 Pattern I – focal (ISR ≤ 10
mm),
 Pattern II – diffuse (ISR > 10
mm),
 Pattern 3 – proliferative (ISR >
10 mm extending outside the
stent)
 Pattern IV – occlusion
(occlusive ISR)
This system was primarily
created concerning BMS-ISR,
but it also has prognostic value
in DES-ISR
17

18. 18

19. Etiopathogenesis of ISR
19

20. Biological factors
 Resistance to antiproliferative drugs.
 Mutations of the gene polymorphism that encode mTOR -
resistance to sirolimus (rapamycin).
 Hypersensitivity reactions to the polymer
 Inflammatory response associated with sirolimus eluting stents
(SES) /everolimus-eluting stent (EES)
 Hypersensitivity reactions to the metallic stent platform
20

21. Arterial factors
 High-shear stress areas like carina of the bifurcation can
potentially limit progression of atherosclerosis,
 Low-shear stress areas like ostium of a bifurcation may lead to
promotion of atherosclerosis or enhancement of neointimal
proliferation.
 Positive vessel remodeling may be also a contributable factor
for development of DES-ISR.
21

22. 22

23. Stent factors
 stent underexpansion
( major risk-factor for ISR)
 stent malapposition
 stent fracture,
 type of DES (type of drug
and polymer release
kinetics),
23

24. Stent factors
 nonuniform drug deposition/ distribution,
 strut thickness and polymer disruption or peeling.
 Type of drug and polymer release kinetics
24

25. Stent factors
 thicker stent struts -increased risk from ISR
 Polymer disruption, peeling and cracking -increasing the risk
for ISR
 aggressive kissing-balloon postdilatation
 After using non-compliant balloons on high pressure
atmospheres.
25

26. Implantation (technical) factors
 Barotrauma outside stented segment
 Stent gap
 Residual uncovered atherosclerotic plaques
26

27. Noncardiac surgery after percutaneous coronary
intervention
 5 to 10% of patients
undergo noncardiac surgery
within one year of stent
implantation
 risks of ACS with premature
cessation and bleeding with
continuation of antiplatelet
therapy
27

28. COMPLICATIONS
 patients who undergo major noncardiac surgery within six
weeks, and particularly within two weeks, of PCI with bare-
metal (BMS) or drug-eluting stents (DES) have an increased
risk of adverse cardiovascular events.
 These events are often due to stent thrombosis, which lead to
high rates of myocardial infarction (50 to 70 percent) and
death (10 to 40 percent
28

29. Causes
• Premature cessation of antiplatelet therapy
• Prothrombotic and proinflammatory effects of surgery
• Incomplete strut coverage
29

30. 30

31. Noncardiac surgery after percutaneous coronary
intervention
• The importance of the continuation of antiplatelet therapy in
the perioperative period was evaluated and confirmed in a
multicenter, retrospective study of 666 patients with prior
coronary stenting who subsequently underwent cardiac or non-
cardiac (86 percent) surgery
31

32. Noncardiac surgery after percutaneous coronary
intervention
• Comparing those who discontinued therapy to those who did
not, the following findings were noted:
• The rate of MACE was higher (7.5 versus 0.3 percent; p =
0.027)
• After adjustment, perioperative antiplatelet discontinuation
was the strongest independent predictor of MACE
32

33. Noncardiac surgery after percutaneous coronary intervention
• Continuation of aspirin was associated with a significantly
lower risk of MACE
• For non-CABG surgical patients, aspirin alone or with
P2Y12 receptor blocker increases the risk of bleeding by as
much as 20 and 50 percent, respectively, and these rates are
dependent on the location of the surgery . This excess bleeding
leads to an increase in red blood cell transfusion, but not to an
increase in surgical mortality or morbidity
33

34. Approach to a patient for major surgery following recent
coronary artery stenting
• No accepted standard approach
• Multidisciplinary discussion should take place.
• The key questions are
• When was the PCI done?
• What is the type of stent?
• How many stents were placed?
• Was the revascularization complete?
34

35. Approach to a patient for major surgery following recent
coronary artery stenting
• Drug regime and any irregularities of the treatment?
• History of any adverse cardiac event/stent thrombosis?
• Urgency of surgery? / Can the surgery be delayed?
• Bleeding risk during surgery?
• History of conditions prone to stent thrombosis
• Whether antiplatelet medication is to be maintained in
perioperative period or stopped before operation?
• Investigations for platelet count and platelet function should be
undertaken. Whole blood and platelet concentrates should be
arranged prior to surgery.
35

36. 36

37. 37

38. Approach to a patient for major surgery following recent
coronary artery stenting
• low risk for bleeding, continue DAPT
• Intermediate-bleeding-risk case-by-case basis.
• complex stent procedures and co-morbidities,
continue DAPT
38

39. Approach to a patient for major surgery following
recent coronary artery stenting
• High-bleeding-risk surgical procedures Patients with 12
months completed of DAPT and low risk for thrombosis of the
coronary artery stents can stop clopidogrel and ticagrelor 5
days prior to surgery and prasugrel 7 days before surgery
while continuing ASA.
• DAPT should be restarted as soon as possible postoperatively
(ideally within 24 hours) with a loading dose of 300 mg - 600
mg clopidogrel, or prasugrel 60 mg, or ticagrelor 180 mg.
39

40. Approach to a patient for major surgery following
recent coronary artery stenting
• For patients with coronary stents with high risk for thrombosis
presenting for high-risk bleeding surgical procedures, “bridge”
therapy has been suggested.
• Short-acting GP IIb/IIIa inhibitors, -tirofiban or eptifibatide,
as a bridge between the time of the thienopyridine
discontinuation and surgery.
• Given as infusion and requires patient admission to the
hospital 3 days after the discontinuation of thienopyridines
40

41. Approach to a patient for major surgery following recent
coronary artery stenting
• Infusion is stopped 4 to 6 hours prior to surgical
procedure and restarted as soon as possible after the
surgery
41

42. Approach to a patient for major surgery following recent
coronary artery stenting
• Cangrelor, an investigational parenteral, reversible,
direct P2Y12 platelet inhibitor with its extremely
short (5 to 9 minutes) half-life, may present an
alternative for “bridge” therapy in the near future.
42

43. Approach to a patient for major surgery following
recent coronary artery stenting
• Platelet Transfusion
• Blood transfusions
• hemorrhage that continues despite the usual
hemostatic techniques, however, platelet
transfusion may be considered as a strategy to
reverse bleeding, even if platelet count is
normal.
43

44. Take home message
• Stent thrombosis -Most
feared complication
• DES -restenosis rates 0%-
16%
• Perioperatvie cardiac
events are often due to
stent thrombosis
• Most consistently
reported predictors are
early DAPT
discontinuation
44

45. Take home message
• low risk for bleeding, continue DAPT
• Intermediate-bleeding-risk case-by-case basis.
• complex stent procedures and co-morbidities,
continue DAPT
• patients with stents in need of urgent surgical
procedures If the time is less than one year (or less
than one month for BMS), then the DAPT has to be
continued throughout, except for surgeries in
enclosed spaces.
45

46. 46

47. 47