Bare-Metal Stents Versus Drug-Eluting Stents for Primary Angioplasty: Long-Term Outcome

Percutaneous transluminal coronary intervention (PCI) is the most used myocardial revascularization technique for patients with coronary artery disease. Primary PCI with stent implantation is widely considered the gold standard for the treatment of ST-elevation myocardial infarction patients. Coronary stents, compared with balloon angioplasty, have reduced focal lesion restenosis. To reduce in-stent restenosis, drug-eluting stents (DES) were designed to locally release drugs inhibiting neointimal growth. Recent concerns have emerged on the potential higher risk of stent thrombosis with DES that might be even more pronounced among myocardial infarction patients. For these reasons, DES for primary PCI remains an “off-label” use. In the last several years, a number of randomized trials and registries have tested the safety and efficacy of DES in primary PCI. Data from these studies were analyzed in several meta-analyses, reasonably consistently demonstrating that the use of DES significantly decreased the need for revascularization without an increase in the incidence of death, recurrent infarction, or stent thrombosis at long-term follow-up.     

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.     

Future stent drug delivery systems

Drug-eluting stents (DES) with antiproliferative drugs attached via polymers on the stent surface have reduced in-stent restenosis and repeat revascularization compared with bare metal stent (BMS) across nearly all lesion and patient subsets. However, the small number of patients with in-stent restenosis after DES treatment still exists. Furthermore, concerns about long-term safety of DES are raised, particularly regarding the higher-than-expected late-event thrombosis. There is no doubt that the DES will continue to play a pivotal role in the treatment of coronary artery disease, yet future designs need to incorporate features that reduce thrombosis and promote endothelialization along with maintaining the efficacy. This review focuses on novel generation of DES, discussing new programs, including new antiproliferative agents, novel polymeric and non polymeric stents.     

Long-term outcomes after management of restenosis or thrombosis of drug-eluting stents.

OBJECTIVES: The purpose of this study was to examine the outcomes of patients who developed coronary in-stent restenosis (ISR) or stent thrombosis (STH) inside drug-eluting stents (DES). BACKGROUND: Drug-eluting stents have markedly reduced the incidence of restenosis. However, when restenosis occurs within a DES, its optimal management remains unclear. METHODS: We retrospectively analyzed clinical and angiographic data from 92 patients who underwent revascularization for ISR (n = 84) or STH (n = 8) within a DES at our institution. Regular follow-ups were available up to 2 years. We recorded the occurrence of major adverse cardiac events (MACE), defined as deaths from all causes, myocardial infarction (MI), or target lesion revascularization (TLR), among patients treated by the "DES sandwich" technique or by other treatment methods. RESULTS: In-hospital MACE included 1 periprocedural MI and 2 deaths. Over a mean follow-up of 15 +/- 6 months, the overall rates of death, MI, and TLR were 8.7%, 2.2%, and 30.6%, respectively. By actuarial analysis, the 12-month TLR and MACE rates were 28.2% and 42.9%, respectively. CONCLUSIONS: Current treatments of ISR or STH in DES are associated with a high long-term rate of MACE.     

Drug-Eluting Stents, Restenosis and Revascularization

Several meta-analyses have demonstrated the superiority of drug-eluting stents (DES) in reducing the incidence of restenosis, target vessel revascularization and target lesion revascularization compared to their predecessor, the bare-metal stent. In comparing Cypher and Taxus stents, the two most recent meta-analyses have given the edge to the Cypher. However, it must be stressed that the superiority of one DES over another remains debatable due to ever changing "real-world data" compared to those attained from randomized trials. The newer sirolimus analogs and selective inhibitors are challenging the old guard in their quest to further limit restenosis. So too are the newer "high-tech" polymers and additionally by using more biodegradable material in the stent's design. Stents aimed at targeting lesions are a new armament in the battle against restenosis and together with combination therapies are exciting key areas to watch. The ideal way to treat a DES in-stent restenosis is still a challenge and hence the impetus is to avoid it from happening in the first place.     

Comparison of long-term clinical and angiographic outcomes following implantation of bare metal stents and drug-eluting stents in aorto-ostial lesions

Percutaneous coronary intervention (PCI) to aorto-ostial (AO) lesions is technically demanding and associated with high revascularization rates. The aim of this study was to assess outcomes after bare metal stent (BMS) compared to drug-eluting stent (DES) implantation after PCI to AO lesions. A retrospective cohort analysis was conducted of all consecutive patients who underwent PCI to AO lesions at 2 centers. Angiographic and clinical outcomes in 230 patients with DES from September 2000 to December 2009 were compared to a historical control group of 116 patients with BMS. Comparison of the baseline demographics showed more diabetics (32% vs 16%, p = 0.001), lower ejection fractions (52.3 ± 9.7% vs 55.0 ± 11.5%, p = 0.022), longer stents (17.55 ± 7.76 vs 14.37 ± 5.60 mm, p <0.001), and smaller final stent minimum luminal diameters (3.43 ± 0.53 vs 3.66 ± 0.63 mm, p = 0.001) in the DES versus BMS group. Angiographic follow-up (DES 68%, BMS 66%) showed lower restenosis rates with DES (20% vs 47%, p <0.001). At clinical follow-up, target lesion revascularization rates were lowest with DES (12% vs 27%, p = 0.001). Cox regression analysis with propensity score adjustment for baseline differences suggested that DES were associated with a reduction in target lesion revascularization (hazard ratios 0.28, 95% confidence interval 0.15 to 0.52, p <0.001) and major adverse cardiac events (hazard ratio 0.50, 95% confidence interval 0.32 to 0.79, p = 0.003). There was a nonsignificantly higher incidence of Academic Research Consortium definite and probable stent thrombosis with DES (n = 9 [4%] vs n = 1 [1%], p = 0.131). In conclusion, despite differences in baseline characteristics favoring the BMS group, PCI with DES in AO lesions was associated with improved outcomes, with lower restenosis, revascularization, and major adverse cardiac event rates.     

The risks and benefits of drug-eluting stents in the setting of STEMI

Primary percutaneous coronary intervention (PCI) represents the treatment of choice in patients with ST-segment elevation myocardial infarction (STEMI). In randomized trials excluding STEMI patients, using drug-eluting stents (DES) significantly reduced angiographic restenosis and target vessel revascularization compared with bare metal stents (BMS); however, concerns exist regarding an increased follow-up incidence of stent thrombosis after DES implantation. This complication, which is associated with higher mortality and morbidity rates, may be more frequent among STEMI patients receiving DES versus BMS. Various registries, randomized trials, and two recent meta-analyses on patients undergoing primary PCI have shown that using DES is safe and is associated with significantly reduced rates of restenosis and repeat intervention without an increased risk of myocardial infarction or stent thrombosis at intermediate-term follow-up. However, large trials with hard clinical end points and longer follow-up are needed before routine DES use can be recommended in patients undergoing primary PCI.     

How to approach drug-eluting stent restenosis

Drug-eluting stents (DES) have been a major advance in percutaneous coronary intervention reducing restenosis and repeat revascularization. The application of DES to the treatment of complex lesion and patient subsets has resulted in significant rates of DES restenosis or failure. Though predominantly focal, substantial rates of non-focal DES restenosis are being observed. Non-focal disease most likely represents a resistant process that will remain a therapeutic challenge. An understanding of the causative mechanical and biological factors is essential for the prevention and treatment of DES restenosis. Robust data relating to the treatment efficacy for this problem is lacking. At present, repeat DES or vascular brachytherapy appear to the best available options. Evidence from randomized controlled trials and large registries is required to establish a formal treatment approach. We provide guidelines based on current available evidence.     

Results and predictors of angiographic restenosis and long-term adverse cardiac events after drug-eluting stent implantation for aorto-ostial coronary artery disease

The correlates of angiographic and clinical outcomes after drug-eluting stent (DES) implantation for aorto-ostial lesions remain unknown. This study evaluated long-term results of DES implantation for aorto-ostial lesions and determined risk factors for restenosis and adverse cardiac events. In total, 184 consecutive patients who underwent DES implantation for aorto-ostial lesions were investigated (DES group) compared with 172 consecutive patients treated with bare metal stents before the introduction of DESs (pre-DES group). Major adverse cardiac events (MACEs) were defined as death, Q-wave myocardial infarction, and need for target lesion revascularization. The DES group had significantly higher risk clinical and procedural profiles than the pre-DES group. Procedural success rates were 99.5% in the DES group and 100% in the pre-DES group (p = 1.0). The DES group had a significantly lower incidence of in-segment restenosis (10.5% vs 26.0%, p = 0.001) and target lesion revascularization (4.3% vs 11.6%, p = 0.011). Cumulative MACE rates at 1 year were 6.5% in the DES group and 13.4% in the pre-DES group (p = 0.03). By multivariate analysis, treatment of bypass graft, treatment of in-stent restenosis, and reference vessel diameter were predictors of restenosis, and only reference vessel diameter (hazard ratio 0.20, 95% confidence interval 0.05 to 0.75, p = 0.017) inversely correlated with 1-year MACEs after DES implantation. In conclusion, DES implantation for aorto-ostial lesions is associated with a significant decrease in restenosis and MACEs compared with the pre-DES phase. Treatment of bypass graft and in-stent restenosis and reference vessel size were identified as predictors of restenosis and/or long-term MACEs after DES implantation.     

Intracoronary radiation therapy for multi-drug resistant in-stent restenosis: initial clinical experience.

While randomized clinical trials have demonstrated the excellent efficacy of sirolimus-eluting stents (SES) for de novo lesions, the optimal treatment for SES-restenosis is not known. Management may include stand-alone balloon angioplasty, repeat SES implantation, or placement of a drug-eluting stent (DES) with an alternative antiproliferative agent (i.e., a paclitaxel-eluting stent, PES). The appropriate management strategy for recurrent restenosis after PES implantation for SES restenosis is even less clear. We report the initial clinical experience with intracoronary radiation therapy (ICRT) for multi-DES resistant restenosis. We performed ICRT in five patients with recurrent restenosis after treatment with both SES and PES. Over a median follow-up of 256 days (range 75-489 days), one patient had a target lesion revascularization at 182 days and subsequently died at 483 days following the procedure. Our findings support the further study of this management approach.     

Correlates of clinical restenosis following intracoronary implantation of drug-eluting stents

Despite significant decreases in restenosis and repeated intervention achieved using drug-eluting stents (DESs), the benefit has not been homogenous across all patient and lesion subsets. Identification of correlates of DES restenosis may allow a differing management approach and lead to improved patient outcomes. The study population consisted of 3,535 consecutive patients (5,046 lesions) who underwent successful sirolimus- or paclitaxel-eluting stent implantation for >or=1 native coronary artery or bypass graft lesion from April 2003 to September 2006. From this cohort, 197 patients (237 lesions) were identified to have in-stent restenosis (ISR) requiring revascularization within 12 months of stent implantation. This group was compared with the remainder of the patient population. Logistic regression analysis was performed to identify independent predictors of DES ISR. Independent correlates of DES ISR using multivariate analysis included both clinical and procedural factors. Clinical predictors were age, hypertension, and unstable angina. Procedural predictors were left anterior descending artery intervention, number of stents implanted, stented length/lesion, and lack of intravascular ultrasound guidance. Implantation of >or=3 stents was associated with a significantly higher restenosis risk (9.7% vs 5.1%; p=0.0003). A 10-mm increase in stented length was associated with an adjusted odds ratio of 1.18 (95% confidence interval 1.03 to 1.35). Diabetes, stent diameter, and stent type were found not to be predictive of DES ISR. In conclusion, correlates of DES ISR included both clinical and procedural factors. Limiting the number of stents and stented length, in addition to intravascular ultrasound guidance, may minimize DES ISR.     

冠状动脉支架置入术后不同类型支架再狭窄形式分析

目的通过分析冠状动脉支架置入后造影复查的影像资料,寻找不同支架再狭窄的特点。方法入选行冠状动脉病变介入治疗后造影复查的846处病变,对再狭窄病变行再狭窄形式分析。结果裸支架和药物支架再狭窄中支架近端局限性再狭窄分别占5.69%和33.67%(P=0.000),而支架内弥漫性再狭窄分别占29.27%和9.18%(P=0.000),弥漫性狭窄累及支架两端的分别为20.33%和6.12%(P=0.003),闭塞性再狭窄发生率分别为9.76%和10.20%(P=0.912)。雷帕霉素及其衍生物释放支架和紫杉醇释放支架再狭窄支架边缘局限性再狭窄分别为47.06%和25.00%(P=0.037),支架内弥漫性狭窄分别为1.96%和16.67%(P=0.018)。结论药物支架改变了支架再狭窄模式,弥漫型转为局限型;闭塞性再狭窄时药物支架以支架近端闭塞为主,裸支架以支架内闭塞为主;紫杉醇药物释放支架弥漫性再狭窄发生率较雷帕霉素释放支架有所增加。     

Drug-eluting stent thrombosis

When compared to bare metal stents (BMS), drug-eluting stents (DES) are associated with a dramatic reduction in restenosis and target lesion revascularization. However, the benefit of DES is limited to restenosis, and DES utilization does not translate into reductions in death or myocardial infarction. Additionally, concern exists regarding the long-term safety of DES, as there appears to be a small but real increase in late (LST) and very late stent thrombosis (VLST), seen particularly after the discontinuation of antiplatelet therapy. The specter of LST and VLST has curtailed enthusiasm for widespread DES utilization mandating critical appraisal of DES and the optimal role they play in percutaneous coronary intervention. The incidence of DES thrombosis is debated and varies somewhat by definition. The mechanisms are multifactorial, and involve patient, lesion, stent and physician related factors. Some of these factors are modifiable at the physician-patient level, while others are not. This review focuses on DES thrombosis, with particular attention paid to the definitions, incidence, mechanisms and clinical implications.     

Vascular Pathology of Drug-Eluting Stents

Polymer-based sirolimus- (Cypher) and paclitaxel-eluting stents (Taxus), so-called drug-eluting stents (DES), have become the treatment of choice for patients with symptomatic coronary artery disease undergoing percutaneous coronary revascularization (PCI). While these stents have reduced rates of restenosis and late lumen loss compared to bare-metal stents (BMS), late thrombosis, a life-threatening complication of this technology, has emerged as a major concern. Our understanding of the pathophysiology of late DES thrombosis is derived from animal and human pathologic samples taken after implantation of these devices. These data indicate that the DES cause substantial impairment in arterial healing characterized by lack of complete reendothelialization and persistence of fibrin when compared to BMS. This so-called delayed healing is "identified as" the primary substrate of an underlying cause of late DES thrombosis at autopsy. Several additional risk factors for late stent thrombosis include penetration of necrotic core, malapposition, overlapping stent placement, excessive stent length, and bifurcation lesions. These represent additional barriers to healing and should be avoided if DES are to be used in order to minimize the late thrombotic risks of these devices. Since the time course of complete healing with DES is unknown, the optimal duration of antiplatelet treatment remains to be determined.     

Review of percutaneous therapy for bifurcation lesions in the era of drug-eluting stents

Although recent advances in percutaneous coronary interventions (PCI) have led to dramatic expansions in procedural complexity, bifurcation lesions (BL) remain a serious challenge for the interventionalist. Turbulent flow dynamics and high shear stress likely predispose coronary bifurcations to development of atherosclerotic plaques. These lesions comprise 15% to 20% of the total number of coronary interventions. When compared with non-BL interventions, BL interventions demonstrate lower procedural success rates, higher procedural costs, longer hospitalizations, and higher clinical and angiographic restenosis rates. The recent introduction of drug-eluting stents (DES) has resulted in lower incidences of target lesion/ vessel revascularization and reduction of main branch restenosis in this anatomic subset, when compared to historical bare metal stent (BMS) controls. Nonetheless, DES have not resolved the bifurcation PCI problem; and several techniques employing either 1 or 2 stents have emerged. Stenting of the main vessel with provisional side branch stenting seems to be the prevailing approach. While no definitive single BL-PCI technique has been identified, the optimal approach is likely lesion-specific. This paper reviews different treatment modalities for this complex lesion subset, with particular emphasis on the use of DES, as well as new potential therapeutic approaches.     

Use of drug‐eluting stents for chronic total occlusions: A systematic review and meta‐analysis

Aim: To perform a systematic review and meta‐analysis of studies reporting outcomes after drug‐eluting stent (DES) implantation in chronic total occlusions (CTOs). Methods: A review of publications and online databases in January 2010 retrieved 17 published studies that reported outcomes after DES implantation in CTOs: eight uncontrolled studies, seven nonrandomized comparative studies with bare‐metal stents (BMS), one post‐hoc analysis of a randomized trial, and one randomized trial. Data were pooled using random‐effects meta‐analysis models. Results: All published studies evaluated sirolimus‐ or paclitaxel‐eluting stents. All studies reporting comparative angiographic outcomes revealed less binary angiographic restenosis with DES implantation compared to BMS (odds ratio: 0.15, 95% CI: 0.08, 0.26). Over a mean follow‐up period of 18.9 ± 16.5 months, the cumulative incidence of death, myocardial infarction, or stent thrombosis was similar between DES and BMS in all studies. Target lesion revascularization (odds ratio: 0.13, 95% CI: 0.06, 0.26) and target vessel revascularization (odds ratio 0.18, 95% CI: 0.11, 0.31) at 6–12 months were consistently lower among DES‐treated patients. Similar patterns of safety and efficacy event rates were also observed in studies reporting >12 month outcomes. Conclusions: Compared with BMS, treatment of chronic total coronary occlusions with DES is associated with significant reductions in angiographic and clinical restenosis with similar safety. The consistency and magnitude of treatment effect across both individual trials and the pooled analysis establish DES as the preferred therapy for percutaneous revascularization of CTOs. © 2010 Wiley‐Liss, Inc.     

Usefulness of high-pressure post-dilatation to optimize deployment of drug-eluting stents for the treatment of diffuse in-stent coronary restenosis

Drug-eluting stents (DESs) may represent a simple, effective treatment for in-stent restenosis (ISR); however, the underexpansion of stents is a significant cause of target vessel failure. It was hypothesized that high-pressure postdilatation would be necessary to optimize DES expansion and minimize the risk for restenosis when treating patients with ISR. Fifteen patients with diffuse ISR were treated by predilatation (including cutting balloons), DES deployment, and high-pressure postdilatation, with the measurement of luminal and stent dimensions by intravascular ultrasound after each intervention. After initial deployment, DES underexpansion was present in 10 of 15 patients (66%); after high-pressure postdilatation, there was a significant increase in luminal dimensions, including minimum luminal area (4.3 +/- 0.3 to 5.6 +/- 0.4 mm(2), p <0.001) and a doubling in the proportion of patients with optimal stent expansion. At long-term follow-up (median 11 months), target lesion revascularization occurred in 1 patient (7%) because of edge restenosis; there was no restenosis within the DES.     

Percutaneous coronary intervention for unprotected left main disease in very high risk patients: safety of drug-eluting stents

Percutaneous treatment of unprotected left main coronary artery (ULMCA) stenosis using drug-eluting stents (DES) has been suggested as the best approach for patients who are poor surgical candidates. Some concerns have recently been raised regarding the risk of stent thrombosis following DES implantation. This study was performed in order to evaluate the safety of DES, as compared to bare metal stents (BMS), for ULMCA stenosis treatment in very high risk patients with a high likelihood of stent thrombosis. Forty-two consecutive patients were treated with either BMS (20) or DES (22) for ULMCA critical stenosis. Inclusion criteria were: ST elevation myocardial infarction, non-ST elevation myocardial infarction, cardiogenic shock, or logistic European System for Cardiac Operative Risk Evaluation ≥ 13%. At 1 year, one case of late thrombosis and three cases of restenosis were reported in the BMS group and none in the DES group, leading to a significantly inferior rate of target lesion revascularization (20.0 vs. 0%, p = 0.048) and major adverse cardiac events (65.0 vs. 19%, p = 0.004). DES placement for ULMCA stenosis also appears to be a safe therapeutic choice in very high-risk patients, as it provides the benefit of a reduction in restenosis without increasing the risk of early or late stent thrombosis.     

Coronary bifurcation stenting. Current techniques, outcome and possible future developments

Percutaneous treatment of coronary bifurcation lesions remained challenging in the stent era, with restenosis rates greater than 30% and no advantage from the routine use of kissing stents. Drug eluting stents (DES) have dramatically reduced the restenosis rates (RR) in the main vessel, but with conventional T-stenting double digits figures are still reported for the side-branch because of poor ostial coverage. The techniques of kissing stenting able to provide full lesion coverage (Culotte, V-stenting, Crush) have the potential to improve these results but the development of dedicated DES is probably needed to obtain consistently high procedural and long-term success.     

Intravascular ultrasound guidance in drug-eluting stent deployment

The role of routine intravascular ultrasound (IVUS) guidance during percutaneous coronary intervention (PCI) in the bare metal stent era remains controversial. The potential to reduce revascularization was reported without impacting non-fatal myocardial infarction and death. Drug-eluting stents (DES) have realized improved clinical results in patients undergoing PCI but are not free of restenosis and are limited by thrombosis, particularly in more complex lesion types. Stent under-expansion, malposition, and incomplete lesion coverage have been identified as the key mechanisms of DES failure. The identification of these features on IVUS and their subsequent treatment may lead to improved clinical outcomes. Though a clinical benefit is intuitive, results from randomized trials are still needed to justify routine IVUS guided DES implantation. The Authors provide a review of the currently available evidence pertaining to the potential clinical benefit of IVUS guidance in DES implantation.