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Problem associated with Drug eluting stent

PresenterDr PRAVEEN GUPTA

ModeratorDr. Ajith Ananthakrishna Pillai

Date16/09/2016

Departement of Cardiology, JIPMER,

Pondicherry (India)

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Stent thrombosisIntroduction

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%

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Stent thrombosisIntroduction

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

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Definition and classification

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Clinical Presentation,

Chest pain Ischemic electrocardiographic changes in the target

vessel territory. Sudden death, It can be asymptomatic in the setting of collateral

vessels.

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Angiographic characteristics of definite stent thrombosis: role of thrombus grade, collaterals, epicardial coronary flow, and

myocardial perfusion.

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.

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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)

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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

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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

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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

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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

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In-stent RestenosisIntroduction

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.

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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

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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

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Etiopathogenesis of ISR

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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

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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.

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Stent factors stent underexpansion( major risk-factor for ISR) stent malapposition stent fracture, type of DES (type of drug

and polymer release kinetics),

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Stent factors

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

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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.

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Implantation (technical) factors

Barotrauma outside stented segment Stent gap Residual uncovered atherosclerotic plaques

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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

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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

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Causes

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

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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

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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

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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

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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?

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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.

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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

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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.

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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

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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

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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.

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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.

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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

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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.

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