Successful Prasugrel Therapy for Recurrent Left Main Stent Thrombosis in a Clopidogrel Hyporesponder

Stent thrombosis is a life-threatening sequela of drug-eluting stent implantation. Dual antiplatelet therapy with aspirin and thienopyridine is typically used to prevent this catastrophic event. In terms of stent thrombosis, the major concern is the variable response of patients to clopidogrel, and this has raised interest in new antiplatelet agents. We present the case of a 64-year-old woman whom we successfully treated with prasugrel after she had repeated episodes of stent thrombosis caused by a poor response to clopidogrel. This case highlights the potential role of new antiplatelet agents for patients who are undergoing drug-eluting stent implantation.     

Stent thrombosis with drug-eluting stents: a re-examination of the evidence.

The excitement of drug-eluting stents and their promise for reduced restenosis rates have been tempered by recent reports of stent thrombosis. The mechanism of stent thrombosis is multifactorial but appears to be related to delayed endothelialization and healing, late stent malapposition, and antiplatelet resistance. The most important risk factor appears to be the discontinuation of dual antiplatelet therapy. The data from clinical trials suggest that drug-eluting stents are associated with increased incidence of death or myocardial infarction compared with bare metal stents at long-term follow-up, suggesting that the window of thrombotic risk with drug-eluting stents may extend far beyond that for bare metal stents. Measures to possibly decrease the incidence of stent thrombosis include improvements in antiplatelet regimens and newer generation of drug-eluting stents which have biodegradable polymers or are polymer-free. In addition, percutaneous coronary intervention with bare metal stents in patients may be helpful in those known to be intolerant or noncompliant to antiplatelet therapy, have planned procedures or surgeries, or have overwhelming risks which may require discontinuation of dual antiplatelet therapy.     

Drug-Eluting Stent Thrombosis 1,659 Days after Stent Deployment: Case Report and Literature Review

Drug-eluting stents are considered to be superior to bare-metal stents in reducing restenosis rates at 6 months. However, drug-eluting stents appear to be subject to stent thrombosis, a concern that has been reported more frequently in recent times.In November 2003, a 64-year-old man with a medical history of hypertension, type 2 diabetes mellitus, and coronary artery disease underwent percutaneous coronary intervention for the deployment of a sirolimus-eluting stent in the left anterior descending coronary artery. He experienced no complications. More than 4 years later, at age 69, he underwent neurosurgical treatment for a subdural hematoma that resulted from a fall, and he was advised to stop taking aspirin and clopidogrel. Thirty-three days later—1,659 days after stent deployment—he presented with a clinical event that was associated with very late stent thrombosis. After undergoing emergent coronary angiography and the placement of 2 bare-metal stents, he resumed antiplatelet therapy, recovered uneventfully, and was discharged from the hospital in stable condition.To the best of our knowledge, 1,659 days is the longest reported interval between the deployment of a drug-eluting stent and the occurrence of a clinical event that was associated with very late stent thrombosis. Herein, we discuss the case of our patient, review the pertinent medical literature, reinforce the importance of continuous and uninterrupted antiplatelet therapy in drug-eluting stent recipients, and offer considerations regarding the use of drug-eluting stents.Key words: Angioplasty, transluminal, percutaneous coronary/adverse effects; coronary artery disease/therapy; coronary restenosis/epidemiology/etiology/prevention & control; coronary thrombosis/etiology; coronary vessels/pathology; drug-eluting stents/adverse effects; drug therapy, combination; platelet aggregation inhibitors/administration & dosage/therapeutic use; thrombosis/epidemiology/etiology; time factorsDrug-eluting stents (DESs) with sirolimus have reduced the rate of repeat revascularization of target lesions. These stents reduce restenosis rates at 6 months and, for that reason, are considered to be superior to bare-metal stents.¹ However, there have been several reports of very late DES thrombosis (>360 d),² which we review here as we describe the case of our patient. We also offer recommendations to physicians regarding the use of DESs, the value of uninterrupted antiplatelet therapy, and the selection of patients in whom DESs will potentially be deployed.     

Very Late Angiographic Stent Thrombosis with Cyphertrade mark Stent Despite Being on Aspirin Therapy

Late angiographic stent thrombosis after Cyphertrade mark stent implantation has been reported to occur till approximately one year after the procedure and usually soon after the discontinuation of all antiplatelet medication.We report a case of very late stent thrombosis occurring 27 months (790 days) after stent implantation and 13 months after clopidogrel discontinuation despite being on regular aspirin. This case underlines the possible need for long-term dual antiplatelet therapy after implantation of drug-eluting stents.     

Restenosis,Stent Thrombosis,and Bleeding Complications: Navigating Between Scylla and Charybdis

The field of interventional cardiology has significantly evolved over 40 years by overcoming several challenges. The introduction of first-generation drug-eluting stents significantly reduced the rates of restenosis, but at the expense of an increase of late stent thrombosis. Prolonged antithrombotic therapy reduced rates of stent thrombosis, but at the cost of increased bleeding. Although the advent of second-generation drug-eluting stents subsequently reduced the incidence of late stent thrombosis, its permanent nature prevents full recovery of vascular structure and function with accordant risk of very late stent failure. In the present era of interventional cardiology, the tradeoff between stent thrombosis, restenosis, and bleeding presents as a particularly complex challenge. In this review, the authors highlight major contributors of late/very late stent thrombosis while targeting stent restenosis, and they discuss evolutionary advances in stent technology and antiplatelet therapy, to further improve upon the care of patients with coronary artery disease.     

Drug-eluting stents and stent thrombosis: a cause for concern?

Drug-eluting stents, most commonly sirolimus-eluting stents and polymer-based paclitaxel-eluting stents, are now widely used during percutaneous coronary interventions, and have largely replaced bare-metal stents to treat a variety of native coronary artery and saphenous vein graft lesions. Stent thrombosis, a complication of both bare-metal and drug-eluting stents, is associated with significant morbidity and mortality including high rates of myocardial infarction and death. Recently, several studies in the literature have raised concern about increased rates of overall stent thrombosis and late stent thrombosis in drug-eluting stents in the so-called 'real world' where off-label uses of drug-eluting stents are common. Hypersensitivity reactions to the polymers used in drug-eluting stents, delayed endothelialization of the stents, and discontinuation of dual antiplatelet therapy have all been implicated in the pathophysiology of drug-eluting stents stent thrombosis. The incidence of total stent thrombosis as well as late stent thrombosis, however, does not seem to be significantly higher in drug-eluting stents than in bare-metal stents. An important risk factor for stent thrombosis in both types of stents appears to be the premature discontinuation of dual antiplatelet therapy, and physicians should educate their patients about the importance of adhering to dual antiplatelet therapy, given the dire clinical consequences of stent thrombosis.     

Impact of Insulin Resistance on Neointimal Tissue Proliferation after 2nd-Generation Drug-Eluting Stent Implantation

Percutaneous coronary intervention is established as an effective treatment for patients with ischemic heart disease; in particular, drug-eluting stent implantation is known to suppress in-stent restenosis. Diabetes mellitus is an independent risk factor for restenosis, so reducing insulin resistance is being studied as a new treatment approach. In this prospective study, we sought to clarify the factors associated with in-stent restenosis after percutaneous coronary intervention, and we evaluated the homeostasis model assessment of insulin resistance (HOMA-IR) index as a predictor of restenosis.We enrolled 136 consecutive patients who underwent elective percutaneous coronary intervention at our hospital from February 2010 through April 2013. All were implanted with a 2nd-generation drug-eluting stent. We distributed the patients in accordance with their HOMA-IR index values into insulin-resistant Group P (HOMA-IR, ≥2.5; n=77) and noninsulin-resistant Group N (HOMA-IR, <2.5; n=59). Before and immediately after stenting, we measured reference diameter, minimal lumen diameter, and percentage of stenosis, and after 8 months we measured the last 2 factors and late lumen loss, all by means of quantitative coronary angiography.After 8 months, the mean minimal lumen diameter was smaller in Group P than that in Group N (1.85 ± 1.02 vs 2.37 ± 0.66 mm; P=0.037), and the mean late lumen loss was larger (0.4 ± 0.48 vs 0.16 ± 0.21 mm; P=0.025). These results suggest that insulin resistance affects neointimal tissue proliferation after 2nd-generation drug-eluting stent implantation.     

支架内晚期血栓及其防治进展

早期和晚期支架内血栓给当前经皮冠状动脉介入治疗带来棘手的问题,可以导致非致命性心肌梗死和心源性死亡。晚期支架内血栓较少见但往往带来严重后果,多见于药物洗脱支架术后。支架内血栓的发生主要与支架置入技术、病变特征、双重抗血小板治疗效果、局部组织对雷帕霉素或紫杉醇等涂层药物的反应等因素有关。使用新一代药物洗脱支架可能减少晚期支架内血栓发生的风险。     

The Problem of Stent Thrombosis Associated With Drug-Eluting Stents and the Optimal Duration of Dual Antiplatelet Therapy

Drug-eluting stents have significantly reduced the problem of restenosis, but there is an association between drug-eluting stents and stent thrombosis that can be a significant clinical problem resulting in myocardial infarction or death. The risk for stent thrombosis increases in certain clinical situations and has been reduced through the use of dual antiplatelet therapy for prolonged periods. Until new therapies are developed, it is essential that patients who have had drug-eluting stents implanted continue with dual-antiplatelet therapy for at least 1 year and possibly for an indefinite period.     

Stent thrombosis and drug-eluting stents

Coronary stents have been used for the treatment of patients with coronary artery disease (CAD), and significantly improved procedural safety and are associated with a lower rate of restenosis compared with balloon angioplasty alone. Drug-eluting stents (DES) have been dominant for the treatment of CAD with efficacy in significantly reducing both restenosis and target lesion revascularization. However, late and very late stent thrombosis have become a major concern in DES-implanted arteries compared with those treated with bare-metal stents (BMS). This review focuses on the feature of DES thrombosis and pathological examination and dual antiplatelet therapy for prevention of stent thrombosis.Currently, the incidence of stent thrombosis associated with first-generation and second-generation DES remains unclear in data from real-world cohort registry studies. Further studies of larger multicenter trials would give us insight into the specific mechanisms of stent thrombosis among different generations of DES.     

Focused clinical review: periprocedural management of antiplatelet therapy in patients with coronary stents

Coronary stent implantation, particularly drug eluting stents, is now the major method of coronary revascularisation. Following drug-eluting stent implantation dual antiplatelet therapy with aspirin and thienopyridine is recommended for at least 12 months. Premature discontinuation, often at the time of noncardiac surgery, has been associated with stent thrombosis which has a significant risk of death and myocardial infarction. Late (>30 days) and very late (>365 days) stent thrombosis appears to more common with DES and poses the questions of when is it safe to stop antiplatelet therapy post coronary stenting and how to manage patients who need non-cardiac surgery. This article reviews the evidence for stent thrombosis and the peri-operative management of patients with coronary stents and provides an algorithm for patient management based on multidisciplinary assessment of bleeding risk, perioperative cardiac event and stent thrombosis risk.     

Simultaneous Very Late Stent Thrombosis in Multiple Coronary Arteries

We report 2 noteworthy cases of very late stent thrombosis presenting as ST-segment-elevation myocardial infarction, with vastly different manifestations. Both patients were women who had histories of multivessel percutaneous coronary intervention with first-generation sirolimus-eluting stents, in 2005 and 2006. On the more recent occasions reported here, one underwent successful multivessel primary percutaneous coronary intervention, while the other underwent successful multivessel “plain old balloon angioplasty.” Both were discharged from the hospital with advice to stop smoking and to follow a lifelong regimen of aspirin and clopidogrel.On the basis of these two cases and our review of the current literature, we ask whether it is now prudent to recommend lifelong dual antiplatelet therapy after drug-eluting stent deployment. Moreover, in order to account for cases of stent thrombosis that occur ≥5 years after drug-eluting stent implantation, should we perhaps suggest the addition of “extremely late stent thrombosis” to the existing Academic Research Consortium classification?Key words: Aspirin, clopidogrel, coronary restenosis/etiology, coronary thrombosis/etiology, drug delivery systems/adverse effects, immunosuppressive agents, paclitaxel, platelet aggregation inhibitors/therapeutic use, sirolimus/therapeutic use, stent thrombosis, stents, drug-eluting/adverse effects, ST-elevation myocardial infarction, very late stent thrombosisStent thrombosis after percutaneous coronary intervention (PCI) remains a serious concern for both cardiologists and patients. The incidence of stent thrombosis within the first 30 days in patients randomized to receive sirolimus-eluting stents (SES) in clinical trials is reported to be no different from that in patients randomized to a control group receiving bare-metal stents.¹ Stent thrombosis has been reported as late as 17 months,² and more recently as late as 26 months, after SES implantation.³ We report 2 cases of simultaneous very late stent thrombosis in multiple coronary arteries ≥5 years after drug-eluting stent (DES) implantation, presenting as an ST-segment-elevation myocardial infarction (STEMI) despite a regimen of aspirin in patient 1 and both aspirin and clopidogrel in patient 2.     

Triple,simultaneous, very late coronary stent thrombosis

Coronary artery stent thrombosis is an uncommon but potentially catastrophic complication. The risk of very late stent thrombosis (VLST) raises important safety issues regarding the first generation of drug-eluting stents (DES). Although several complex mechanisms for VLST have been suggested and various predictors have been described, its pathophysiology is not completely understood and it is not known whether longer-term dual antiplatelet therapy reduces the risk. We present a rare case of simultaneous very late DES thrombosis in the three vascular territories, following discontinuation of antiplatelet therapy seven years after stent placement, presenting as cardiogenic shock.     

Balancing efficacy and safety of drug-eluting stents in patients undergoing percutaneous coronary intervention

Drug-eluting stents reduce the occurrence of in-stent restenosis and the need for subsequent target vessel revascularization compared with bare-metal stents. However, the safety of drug-eluting stents has been called into question because of an apparent increase in late stent thrombosis, a frequently fatal event. A substantial body of research has focused on determining the magnitude of these competing events, often reaching contradictory results even with analyses of the same data. Although larger, adequately powered, randomized trials are needed to fully assess the net clinical effects of drug-eluting stents compared with bare-metal stents, the evidence seems to suggest that the net clinical benefit of drug-eluting stents may outweigh their risks. The evidence is clearer that premature discontinuation of antiplatelet therapy is an important trigger for stent thrombosis; therefore, patients who are candidates for implantation of drug-eluting stents should be screened for their ability to receive and tolerate uninterrupted antiplatelet therapy longer than is necessary with bare-metal stents. The evidence suggests that drug-eluting stents relieve obstructive coronary artery disease, provide durable mechanical results, and do more good than harm, but all patients also should be given antiplatelet and other optimal medical therapies to achieve the best outcomes.     

合理看待药物洗脱支架晚期血栓问题

冠状动脉支架现广泛应用于冠心病的介入治疗中。支架内血栓是金属裸支架和药物洗脱支架的一个并发症,可导致心肌梗死或死亡。最近,药物洗脱支架引起晚期支架内血栓的问题引起人们的广泛关注。支架血栓的危险因素包括操作因素(如支架贴壁不良、置入支架的数目、支架长度及夹层)、患者及病变因素、过早停用抗血小板药物以及支架释放的药物使内皮延迟愈合等。现对支架晚期血栓的概念、发生的危险因素、防治措施等进行探讨。     

Perioperative management of patients with coronary stents

Perioperative coronary stent thrombosis is a catastrophic complication that can occur in patients receiving both bare-metal and drug-eluting stents. Noncardiac surgery appears to increase the risk that recently-placed stents thrombose, especially when surgery is performed early after stenting, and particularly if dual antiplatelet therapy is discontinued. We reviewed the existing data about the frequency of stent thrombosis after noncardiac surgery and explored the impact of delay from surgery and discontinuation of antiplatelet therapy. We also reviewed the data about the impact of preoperative revascularization in patients known to require noncardiac surgery. Based on these published data, we offer recommendations that can be used to guide the treatment of patients who require noncardiac surgery after having received a stent.     

药物洗脱支架内血栓研究进展

药物洗脱支架能明显降低冠状动脉介入术后支架内再狭窄和靶病变再次血运重建,而支架内血栓发生率虽很低但预后差,是药物洗脱支架的潜在危险,预防支架内血栓形成是冠状动脉粥样硬化性心脏病介入领域的研究热点和难点。     

Recurrent late drug-eluting stent thrombosis upon discontinuation of antiplatelet therapy

Stent thrombosis is a rare but serious complication of percutaneous coronary intervention. Stent thrombosis usually occurs early after stent implantation but can occasionally occur late, especially when drug-eluting stents are used. We report a case of recurrent late paclitaxel-eluting stent thrombosis (8 and 21 months after initial stent implantation) upon discontinuation of dual antiplatelet therapy.     

Drug-eluting stents: current issues

Early stent thrombosis occurs in about 1% to 1.5% of patients with drug-eluting stents, very similar to the rate with bare-metal stents. Late stent thrombosis is more of a concern with drug-eluting stents, with an incidence of at least 0.35%. I would urge caution if you feel you have to stop antiplatelet therapy in patients with drug-eluting stents. While neointima formation peaks at 6 months and then may actually regress with bare-metal stents, it continues to grow with drug-eluting stents--although this process appears to plateau by 4 years with sirolimus. With the others, we have to wait and see. We still don't know the best drug-eluting stent. Trials are under way to compare stents with surgery, and the future brings the arrival of a number of exciting new devices and approaches that are now entering clinical trials.     

Frequency of and risk factors for stent thrombosis after drug-eluting stent implantation during long-term follow-up

Despite concerns regarding the long-term safety of drug-eluting stent (DES) implantation because of late-onset stent thrombosis, the actual incidence of stent thrombosis after 1 year is unknown. We investigated the incidence, risk factors, and association of antiplatelet therapy interruption for the development of stent thrombosis after DES implantation during long-term follow-up. A total of 1,911 consecutive patients with DES implantation were enrolled (sirolimus-eluting stents in 1,545 patients, 2,045 lesions; paclitaxel-eluting stents in 366 patients, 563 lesions). During long-term follow-up (median 19.4 months, interquartile range 15.3 to 24.3), 15 patients (0.8%, 95% confidence interval 0.5% to 1.3%) developed stent thrombosis within 6 hours to 20.4 months. Eleven patients (0.6%, 95% confidence interval 0.3% to 1.0%) had late thrombosis (median 6.1 months). The incidence of stent thrombosis was 3.3% (4 of 121 patients) in patients with complete interruption of antiplatelet therapy (vs 0.6% in those without, p = 0.004) and 7.8% (5 of 64 patients) with premature interruption of aspirin or clopidogrel, or both (vs 0.5% in those without, p < 0.001). Independent predictors of stent thrombosis were premature antiplatelet therapy interruption, primary stenting in acute myocardial infarction, and total stent length. Stent thrombosis also developed while patients were on dual antiplatelet therapy (all patients with acute/subacute stent thrombosis and 36% of those with late stent thrombosis; 47% of total with stent thrombosis). In conclusion, stent thrombosis occurred in 0.8% after DES implantation during long-term follow-up. The incidence of late stent thrombosis was 0.6%, similar to that for bare metal stents. The predictors of stent thrombosis were premature antiplatelet therapy interruption, primary stenting in acute myocardial infarction, and total stent length.