Drug-Eluting Stent and Coronary Thrombosis

Abstract

Abstract-Although rare, stent thrombosis remains a severe complication after stent implantation owing to its high morbidity and mortality. Since the introduction of drug-eluting stents (DES), most interventional centers have noted stent thrombosis up to 3 years after implantation, a complication rarely seen with bare-metal stents. Some data from large registries and meta-analyses of randomized trials indicate a higher risk for DES thrombosis, whereas others suggest an absence of such a risk. Several factors are associated with an increased risk of stent thrombosis, including the procedure itself (stent malapposition and/or underexpansion, number of implanted stents, stent length, persistent slow coronary blood flow, and dissections), patient and lesion characteristics, stent design, and premature cessation of antiplatelet drugs. Drugs released from DES exert distinct biological effects, such as activation of signal transduction pathways and inhibition of cell proliferation. As a result, although primarily aimed at preventing vascular smooth muscle cell proliferation and migration (ie, key factors in the development of restenosis), they also impair reendothelialization, which leads to delayed arterial healing, and induce tissue factor expression, which results in a prothrombogenic environment. In the same way, polymers used to load these drugs have been associated with DES thrombosis. Finally, DES impair endothelial function of the coronary artery distal to the stent, which potentially promotes the risk of ischemia and coronary occlusion. Although several reports raise the possibility of a substantially higher risk of stent thrombosis in DES, evidence remains inconclusive; as a consequence, both large-scale and long-term clinical trials, as well as further mechanistic studies, are needed. The present review focuses on the pathophysiological mechanisms and pathological findings of stent thrombosis in DES.

DMSO inhibits human platelet activation through cyclooxygenase-1 inhibition. A novel agent for drug eluting stents?

“…Findings from the present study reinforce the concept that DMSO is an interesting alternative for the coating of DES where currently employed drugs do not completely address the risks of stent thrombosis [4,5,14,15,17,20,31,34] and, in addition, were shown to induce the expression of TF [29,32,38].…”

“…Even though coronary bare metal stents (BMS) and drug-eluting stent (DES) implantation greatly improved prognosis of ACS patients, acute and sub-acute stent thrombosis still remain a serious concern [4,5,14,15,17,20,31,34]. In line with this, we recently showed that drugs released from DES enhance tissue factor (TF), a key trigger for thrombosis and thus could play a paradoxical role in eliciting stent thrombosis [29,32].…”

Inflammation and Delayed Endothelization With Overlapping Drug-Eluting Stents in a Porcine Model of In-Stent Restenosis

“…14 The incidence of stent thrombosis in the modern era of stent deployment varies from a low of 0.5% to 1.9% with BMS implantation, the same as with DES implantation. [15][16][17] To prevent stent thrombosis, clopidogrel 75 mg/day should be given for at least 6 months after DES implantation and, ideally, up to 12 months in patients who are not at high risk of bleeding, but there has been debate regarding how long such therapy should continue.…”

Very late drug-eluting stent thrombosis after nonsteroidal anti-inflammatory drug treatment despite dual antiplatelet therapy

“…Within the first 30 days, the frequency of stent thrombosis is similar after either bare metal stent or drug-eluting stent (DES) implantation, when dual antiplatelet therapy is maintained (1). Recently, concerns have emerged about the high risk of late stent thrombosis (more than 30 days) after DES implantation due to delayed coronary endothelization, late stent malapposition or aneurysm formation (2). Based on a meta-analysis of multicentre, randomized studies, the predicting factors of late stent thrombosis include stent length and the discontinuation or ineffectiveness of thienopyridine-based antiplatelet therapy (1).…”