Risk factors for the development of coronary stent thrombosis By Ahmed Farouk Assistant Lecturer of Cardiology Tanta University

Introduction  Stent Thrombosis ( ST) is a fatal and catastrophic complication  With the introduction of P2Y12-receptor antagonists for platelet inhibition in combination with ASA, the incidence of ST decreased substantially

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Incidence and Prognosis of ST  The incidence of ST (1% – 2% ) most of them occur in the first 10 days post implantation and is rare after one month with use of BMS but some cases reported up to > 5 Y  Outcome of ST is poor • (10%- 20%) present by sudden death • ( 50% - 80% ) present by AMI • Who survive are at increased risk of recurrent ST

Definition  According to Academic Research Consortium (ARC) ST can be defined as • “Definite” ST: Either angiographic or postmortem evidence of thrombotic stent occlusion • “Probable” ST: Any unexpected death within 30 days of stent implantation, or any MI in the territory of the implanted stent irrespective of time • “Possible” ST: Any unexplained death beyond 30 days until the end of follow-up

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Definition • Early ST: occurring in the first 30 days after stent implantation • Late ST: between 1 month and 1 yr after stent implantation • Very late ST: beyond 1 yr  Some authors divide early ST • Acute ST: during the first 24h • Sub acute ST: after the first 24h till 30 days

BMS versus DES in ST • ST has been evaluated in RCTs , “real-world” registries, and meta-analyses. • RCTs have demonstrated similar incidences of death and MI for both stent types. • Observational “real-world” data base demonstrate an apparent reduction in mortality favoring DES.

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BMS versus DES in ST • Both RCTs and observational studies demonstrate substantial reduction in TVR with DES • Beyond 1-year DES has a small but definite increased risk for very late ST

Class Effect Analyses • Whether ST rate vary among different DES remains controversial. • The SPIRIT IV (Clinical Evaluation of the Xience V Everolimus ES System in the Treatment of Patients with De Novo Native Coronary Artery Lesions) compared Xience V everolimus-ES with with Taxus PES • At 1 year, definite/probable ST occurred less frequently following Xience V (0.3% vs. 1.1%; p 0.003).

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Class Effect Analyses • COMPARE (EES and PES in Real-Life Practice) study of 1,800 real-world patients • Found that definite/probable ST at 1 year was less frequent following the Xience V versus the Taxus Liberté (0.7% and 2.6%, respectively; p 0.002) despite similar DAPT compliance • Endeavor IV trial (Endeavor DES Versus the Taxus in De- Novo Native Coronary Artery Lesions) • Found lower incidence of very late (1 year) ST with Endeavor zotarolimus- ES versus Taxus DES (0.1% vs. 1.5%, respectively; p 0.004)

Risk factors for ST Stent factors Patient factors Lesion Factors Procedural factors

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Risk factors for ST  Stent factors: • Hypersensitivity to drug coating or polymer • Incomplete Endothelialization • Stent design • Covered stents

Risk factors for ST  Patient factors • PCI for acute ACS, STEMI • DM • RF • Impaired LV function • Premature cessation of DAPT • ASA non responsiveness • Clopidogrel non responsiveness • Malignancy

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Risk factors for ST  Lesion Factors • Lesion/stent length • Vessel/stent diameter • Complex lesions (bifurcation lesions,chronic total occlusions) • Saphenous vein graft target lesion • Stasis • Highly thrombotic lesions

Risk factors for ST  Procedural factors • Inadequate stent expansion/sizing • Incomplete stent apposition • Stent deployment in necrotic core with thrombus and plaque prolapse through stent struts • Residual edge dissection • Brachy-therapy

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Pathophysiology OF ST  Impaired Reendothelialization  Thrombogenicity of the Stent  Endothelial Shear Stress & stent malapposition  Stent Deployment in Highly Necrotic core  Disruption of Vulnerable Plaques Just Proximal or Distal to the Stent  Discontinuation of DAP ,Genetic factors and drug interactions

Pathophysiology OF ST  Impaired Reendothelialization • Impaired neointimal formation specially with DES increase the thrombogenicity of the stent as the drug prevents cell growth and delays arterial wall healing and predispose to chronic inflammatory state Circulation February 27, 2007

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Pathophysiology OF ST

Circulation February Temporal sequence of reendothelializationin BMS and DES. 27, 2007

Pathophysiology OF ST  Thrombogenicity of the Stent • ST is more with open-cell versus a closed-cell stent. • Polymers of the Cypher and Taxus DES provoke chronic eosinophilic infiltration of the arterial wall, suggestive of hypersensitivity reactions in a small number of cases

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Pathophysiology OF ST • drugs loaded on DES may exert a prothrombogenic effect. (sirolimus) and Paclitaxel Circulation February 27, 2007

Pathophysiology OF ST  Endothelial Shear Stress & stent malapposition • In normal arteries there is balance among prothrombotic and antithrombotic factors. • Low ESS occurs distal to malappositioned stent struts, undersized stents , with incomplete reendothelialization and at sites of ostia in bifurcational lesions • Low ESS attenuates the endothelial expression of NO, prostacyclin and tPA, shifting the balance toward a prothrombotic state

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Pathophysiology OF ST • Hihg ESS At the site of malappositioned stent struts or stent overlap which activates platelets to release thromboxane A2 and ADP, leading to platelet aggregation

JACC Vol. 59, No. 15, 2012. April 10

Pathophysiology OF ST Stent Deployment in Highly Necrotic Atherosclerotic Plaques With Extensive Plaque Prolapse • Neointimal growth occurs from noninjured arterial edges of rupured plaque. • In highly necrotic plaques, stent struts penetrate deeply into the lipid core and are not in contact with the vessel wall which delays endothelialization

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Pathophysiology OF ST  Disruption of Vulnerable Plaques Just Proximal or Distal to the Stent • Plaque rupture that occurs in close proximity to a stent can extend to the adjacent stented segment and present as ST

Pathophysiology OF ST  Discontinuation of DAP ,Genetic factors , drug interactions • Premature stop of DAP with DES before 6 m • Genetic variation in 1 or more of the cytochrome P450 particularly the reduced-functioning CYP2C19*2 allele • Drug inter actions with (PPI- CCB)

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Pathophysiology OF ST • RCT involving 3,600 clopidogrel-treated patients • demonstrated no difference in cardiovascular outcomes by omeprazole treatment

Pathophysiology OF ST

JACC Vol. 56, No. 10 Suppl S, 2010

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Take home massage • Stent thrombosis is not a common daily practice however it’s a catastrophic and fatal condition • Discussing the issue of duration of DAP therapy with the patient before choice the type of stent is very important • No increase in incidence of ST with DES compared to BMS • 2nd generation DES have less incidence of stent thrombosis • It is important to understand the risks for developing ST to prevent it

Take home massage • Good preparing of the lesion and use rotational atherectomy in highly calcified lesion to prevent malapposition • Use of high pressure balloon for post dilatation when needed to achieve good heamodynamic profile of the stent is very important • Use of IUVS or OCT when available to assess stent position on selected cases • Till now no strong data to support the routine platelet activity test to detect clopidogrel resistance • Also no strong data supporting the prevention of use of PPI

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