Early restenosis after drug-eluting stent implantation: A putative role for platelet activation

Abstract

D rug-eluting stents (DES) are coated with antiproliferative agents that reduce neointimal formation (1) and substantially reduce restenosis compared with bare metal stents (2,3). However, the eluted drug inhibits stent endothelization, potentially rendering the inner stent surface more thrombogenic, and raises concern about a higher risk of stent thrombosis (4).In the present report, the occurrence of in-stent restenosis is documented in two patients after DES deployment at exactly the same sites where subacute stent thrombosis had occurred. CASE PRESENTATIONSCase 1 A 65-year-old man was admitted for effort angina three years after bypass surgery with the left internal mammary artery to the left anterior descending coronary artery (LAD), as well as a single saphenous vein graft sequentially anastomosed to the first diagonal, and first and second obtuse marginal (OM) branches. Coronary angiography documented the patency of the vein graft and the occlusion of the mammary artery graft. The LAD appeared diffusely diseased ( Figure 1A), and a percutaneous coronary intervention (PCI) was therefore performed, with two overlapping sirolimus-eluting stents (Cypher, Cordis, USA) successfully deployed at 1620 kPa ( Figure 1B). Dual antiplatelet therapy with acetylsalicylic acid (160 mg/day) and clopidogrel (300 mg bolus, followed by 75 mg/day) was recommended and initiated. One week after the procedure, the patient experienced angina at rest, and a repeat angiography showed two nonocclusive thrombi inside the distal stent in the LAD ( Figure 1C), with Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow. An infusion of abciximab (ReoPro, Centocor, USA) was initiated (0.25 mg/kg bolus over 3 min, followed by a 12 h infusion at 0.125 μg/kg/min); balloon PCI was then successfully performed. Three months later, the patient had a recurrence of symptoms, and a third angiography showed two focal in-stent restenoses located at exactly the same sites of the previous thrombi inside the LAD ( Figure 1D). Intravascular ultrasound examination identified adequate stent expansion ( Figure 1E-F). The patient underwent a repeat successful balloon PCI, and 12-month dual antiplatelet therapy was recommended. Nine months later, angiography showed full stent patency. Case 2A 72-year-old diabetic hypertensive woman with a previous lateral myocardial infarction underwent coronary angiography for effort angina. Diffuse, severe disease of the LAD was documented ( Figure 2A), with a chronic occlusion of the distal left circumflex artery and an 80% ostial narrowing of the first OM branch. A staged PCI was planned, and acetylsalicylic acid (160 mg/day) and clopidogrel (75 mg/day) were started one week before the intervention. Abciximab was given in the catheterization laboratory as a bolus of 0.25 mg/kg over 3 min, followed by a 12 h infusion of 0.125 μg/kg/min. After a 2.0 mm balloon predilation, four overlapping paclitaxel-eluting stents (Taxus, Boston Scientific, USA) were deployed. However, after stent positioning, two small thrombi were de...

microRNAs Distinctively Regulate Vascular Smooth Muscle and Endothelial Cells: Functional Implications in Angiogenesis, Atherosclerosis, and In-Stent Restenosis

“…Though, concerns have been raised over the long-term safety of the DES, with particular reference to stent thrombosis, essentially due to impaired re-endothelization caused by the nonselective antiproliferative properties of DES [222–224]. As such, when the obstacle of restenosis seemed finally overcome, enthusiasm and euphoria were tempered by epidemiologic data reporting that DES did not ameliorate mortality rates when compared to BMS [225].…”

Surface modification of implanted cardiovascular metal stents: From antithrombosis and antirestenosis to endothelialization

“…A stent coated with bilayered PLGA nanoparticles containing paclitaxel in the inner core and a vascular endothelial growth factor (VEGF) plasmid in the outer layer was developed and was found to promote early endothelium healing while inhibiting SMC proliferation through the sequential release of the VEGF gene and paclitaxel . Moreover, the most used drugs also often have antiproliferative and antithrombotic properties because restenosis may occur at the same site of thrombosis inside DES . These drugs are introduced in “Polymers used for modification” section.…”

“…158 Moreover, the most used drugs also often have antiproliferative and antithrombotic properties because restenosis may occur at the same site of thrombosis inside DES. 159 These drugs are introduced in "Polymers used for modification" section.…”

Plasma-induced nanopillars on bare metal coronary stent surface for enhanced endothelialization

“…The use of metallic stents in general, and in particular polymer-coated, drug-eluting metallic stents (DES), have contributed greatly to reducing the scope of such cardiovascular problems [2,3]. However, the current most significant issue is concern about the increased occurrence of late stent thrombosis, the formation of a blood clot inside the vessel wall at the stented site, when using drug-eluting stents because of potential polymer by-products from delamination, under-endothelialization and other complications due to the surface properties [5,6].…”