Use and long-term outcome of bare metal stent implantation in the drug-eluting stent era

BACKGROUND: Although drug-eluting stents (DES) are widely used today, bare metal stents (BMS) are still frequently employed. We investigated the utilization and clinical outcomes of BMS implantation since we first began using DES. METHODS: The clinical course following percutaneous intervention with de novo implantation of BMS was studied beginning in July 2004, when sirolimus-eluting stents (SES) were first used in our hospital, to August 2006. Outcomes following BMS and SES implantation were compared. RESULTS: BMS implantation was carried out in 160 lesions and SES implantation in 242 lesions. Follow-up coronary angiography was performed for 208 lesions (78 lesions in which BMS were implanted and 130 lesions in which SES were implanted) within 1 year. There were no significant differences in patient characteristics between the SES and BMS groups. Regardless of the reason for BMS implantation, the rates of in-stent restenosis and target lesion revascularization were higher in the BMS group than in the SES group. However, the rate of in-stent restenosis and target lesion revascularization of BMS in lesions with a diameter of 4.0mm or greater was 0%. CONCLUSIONS: In order to reduce the risk of in-stent restenosis and target lesion revascularization, we recommend implantation of BMS with a diameter of 4.0 mm or greater or SES unless it is contraindicated.     

In-stent restenosis in bare metal stents versus sirolimus-eluting stents after primary coronary intervention for acute myocardial infarction and subsequent transcoronary transplantation of autologous stem cells

BACKGROUND: Following stenting for acute myocardial infarction, transcoronary transplantation of granulocyte-colony stimulating factor (G-CSF) mobilized autologous stem cells (ASC) has been shown to result in an increased in-stent restenosis rate of bare metal stents (BMS). HYPOTHESIS: This study sought to compare the extent of neointimal growth in BMS and sirolimus-eluting stents (SES) after primary implantation, and subsequent transcoronary transplantation of G-CSF mobilized stem cells. METHODS: Patients with stenting of the left anterior descending coronary artery for acute anterior myocardial infarction were randomly assigned to receive a BMS or SES. Intracoronary stem cell injection was performed after G-CSF application for at least 4 d and cell apheresis. The angiograms obtained after cell transplantation and after 6 mo were analyzed by quantitative coronary angiography. RESULTS: We performed primary stenting and stem cell transplantion in 16 patients who received a BMS (n = 8) or an SES (n = 8). In 2 patients with a BMS, late stent thrombosis occurred after 58 d and 177 d, respectively. In the remaining patients, control angiography after 6 mo revealed in-stent restenosis of >50% in no patients with SES but in 4 patients with BMS (67%). Late lumen loss and in-stent plaque volume were significantly higher in patients with BMS compared with patients with SES. CONCLUSIONS: Compared with BMS, SES impair in-stent intima hyperplasia after stenting for acute myocardial infarction and transcoronary transplantation of G-CSF mobilized ASC. Copyright (c) 2008 Wiley Periodicals, Inc.     

Stent fracture: a new villain of the village

Stent strut fracture (SSF) may be an important complication after drug-eluting stent (DES) implantation particularly in patients undergoing sirolimus-eluting stent (SES) implantation. The occurrence of SSF at 6 to 9 months after the SES implantation, which was relatively common, resulted in a higher rate of focal in-stent restenosis. Although this angiographic unfavorable outcome did not lead to an increased risk of adverse cardiac events in the current study, we believe that large-scale prospective studies are needed to elucidate the exact pathophysiology and clinical sequela of the stent strut fracture, including bare metal stents.     

Safety of drug-eluting stents in the coronary artery in ST-elevation myocardial infarction at a single high-volume medical center

Several trials have shown the effectiveness of drug-eluting stents (DES) in reducing restenosis. Acute ST-elevation myocardial infarction (STEMI) has been an exclusion criterion in most trials evaluating the safety and efficacy of DES. There is recent randomized trial data evaluating the use and safety of DES for acute myocardial infarction. However, there is a need for "real world" data on the efficacy and safety of DES in STEMI. A single-center retrospective analysis was performed on 188 consecutive patients with STEMI treated with primary or rescue coronary angioplasty between March 2004 and July 2005. The study consisted of 3 groups: 115 patients treated with paclitaxel-eluting stents, 55 with sirolimus-eluting stents, and 18 with bare metal stents. Outcomes were assessed from 12 to 28 months (mean 20, median 19) for major adverse cardiac events (MACEs) including myocardial infarction, in-stent thrombosis, clinical restenosis, and death. There were 4 in-stent thromboses in the paclitaxel group (3.4%) and 2 in-stent thromboses in the sirolimus group (3.6%). The thromboses ranged from acute (within 24 hours) to as late as 8 months. Clinical restenosis occurred in 4 patients (3.4%) in the paclitaxel group and in 2 patients (3.6%) in the sirolimus. None of the 18 patients with bare metal stents had thrombosis or clinical restenosis. There were 7 total deaths, all related to complications from the index STEMI: 1 in the bare metal group, 1 in the sirolimus group, and 5 in the paclitaxel group. The postdischarge MACE rate was 7% with no deaths. In conclusion, the use of DES in acute STEMI is associated with a low postdischarge MACE rate and a 3.5% in-stent thrombosis rate, which is similar to reported rates in earlier randomized trials.     

国产西罗莫司洗脱支架与裸支架治疗急性心肌梗死临床疗效的比较

目的探讨国产西罗莫司洗脱支架与裸支架治疗急性心肌梗死（AMI）临床疗效的差异。方法173例连续行直接PCI的AMI患者随机分为西罗莫司洗脱支架组（87例）和裸支架组（86例）,分析住院期间和支架置入后6个月的支架内血栓、主要心血管事件（包括再次心肌梗死、缺血性靶血管重建和死亡）发生率及6个月再狭窄率。结果两组患者在术后血管通畅、肌酸激酶峰值、心功能和住院期间心脏事件方面差异均无统计学意义（P〉0．05）。两组各有2例支架内血栓（2．4％比2．3％,P〉0．05）。6个月时,国产西罗莫司洗脱支架组的支架内再狭窄率（4．5％比40．0％,P〈0．01）、节段内再狭窄率（6．8％比44．9％,P〈0．01）和主要不良心脏事件发生率（8．0％比24．4％,P〈0．01）显著低于裸支架组。国产西罗莫司洗脱支架组主要心脏事件的减少主要是因为缺血性靶血管重建减少所致（3．4％比11．6％,P〈0．05）。结论与裸支架相比,国产西罗莫司洗脱支架治疗AMI患者并未增加6个月内支架内血栓的发生,而显著降低6个月的再狭窄率和主要心脏事件发生率。     

药物洗脱支架与裸支架介入治疗冠心病的对比研究

目的比较冠心病患者应用药物洗脱支架与应用裸支架的安全性和有效性。方法回顾我院2006—2011年行冠脉支架置入术患者的随访结果,比较应用药物洗脱支架与裸支架的再狭窄率。结果应用药物洗脱支架患者的再狭窄率为8％,应用裸支架患者的再狭窄率为25％,两者相比差异有统计学意义。结论药物洗脱支架较裸支架具有更低的支架内再狭窄发生率。     

Late acute thrombosis after implantation of sirolimus-eluting stent to treat in-stent restenosis

Drug-eluting stents (DES) have significantly reduced the incidence of in-stent restenosis (ISR) compared to bare metal stents (BMS). However, recent randomized trials comparing DES with BMS reported few cases of late DES thrombosis. We report the case of late sirolimus-eluting stent thrombosis occurring 22 months after its elective implantation in a restenotic BMS and soon after the interruption of combined anti-platelet therapy with aspirin and Clopidogrel.     

Frequency of stent fracture as a cause of coronary restenosis after sirolimus-eluting stent implantation

Stent fracture (SF) was suggested as a cause of restenosis after sirolimus-eluting stent (SES) implantation. This study was performed to evaluate the incidence and characteristics of SF to determine its contribution to restenosis in patients with in-stent restenosis (ISR) after SES implantation. From May 2003 to February 2006, SESs were used for percutaneous coronary intervention in 868 patients with 1,109 coronary narrowings. Follow-up coronary angiography was performed in 366 patients (42%), and 26 ISR lesions were observed. These patients were enrolled in this study. SF was divided into 3 types as avulsion, collapse, and partial based on the findings of fluoroscopy, coronary angiography, and intravascular ultrasound study. Of 26 patients with ISR lesions, SF was identified in 10. SF types were avulsion (5 patients), collapse (2 patients), and partial (3 patients). SF was identified at the midshaft (7 patients) and overlap sites (3 patients) of stents. SF was not observed in the 30 patients with ISR after bare-metal Bx Velocity stent implantation. Four patients with SF were treated with paclitaxel-eluting stents. In conclusion, SF is 1 of the leading causes of ISR after SES implantation. Careful fluoroscopic examination is necessary at the time of follow-up angiography to identify this problem.     

Sirolimus-eluting stents inhibit neointimal hyperplasia in diabetic patients. Insights from the RAVEL Trial.

Patients with diabetes mellitus have less favourable outcomes after percutaneous coronary intervention (PCI) than non-diabetics. We performed a subgroup analysis of the multicentre RAVEL trial to examine the impact of the sirolimus-eluting stent (SES) on outcomes in diabetic patients. The RAVEL study randomized 238 patients to treatment with either sirolimus-eluting or bare metal stents. Forty-four patients were diabetic; 19 received sirolimus-eluting stents and 25 were treated with bare metal stents. The differences in outcomes between diabetic and non-diabetic patients treated with SES (n=101) were also assessed. Follow-up angiography was performed at 6 months. Major adverse cardiac events (MACE) defined as death, myocardial infarction (MI), or target lesion revascularization (TLR) were analysed at 12-month follow-up. Six-month in-stent late lumen loss was significantly lower for the diabetic SES than the bare stent group (0.07+/-0.2 vs 0.82+/-0.5mm; P<0.001) and similar to that in non-diabetics treated with SES (-0.03+/-0.27mm). There was zero restenosis in the SES groups (diabetic and non-diabetic) compared to a 42% rate in the diabetic population assigned to bare metal stents (P=0.001). After 12 months, there was one non-Q-wave MI and one non-cardiac death in the diabetic SES group, while 12 patients in the bare metal stent group had MACE (one death, two MI, nine TLR) (P=0.01)-an event-free survival rate of 90% vs 52%, respectively (P<0.01). There were no TLRs in both SES groups compared to 36% rate in the diabetic bare metal stent group (P=0.007).Conclusion Diabetics treated with SES were associated with a virtual abolition of neointimal proliferation and low event rates at long-term follow-up.     

Neue Entwicklungen bei medikamentenfreisetzenden Stents

Although the use of balloon catheters or stents for the treatment of coronary artery lesions shows good short-term results, long-term prognosis due to the occurrence of restenosis in 20%?C30% of patients is less promising. Thus new techniques and mechanical improvements to balloons and stents are always necessary in order to achieve the best possible results from percutaneous coronary intervention. Drug-eluting stents (DES) have improved the principles of bare metal stents (BMS) by neointimal growth inhibition due to local drug release. DES can significantly reduce the incidence of in-stent restenosis. These benefits and lower costs compared to surgical treatment make the DES a more attractive alternative for the treatment of coronary heart disease. Currently, the CYPHER Sirolimus-eluting stent (SES) by Cordis (approved by the FDA on 24th April 2003), the TAXUS Express and the LIBERTE Paclitaxel-eluting stent (PES) by Boston Scientific (approved by the FDA on 4th March 2004 and October 10, 2008), the Endeavor Zotarolimus-eluting stent (ZES) by Medtronic (approved by the FDA on 1st February 2008) and the Xience V Everolimus-eluting stent (EES) by Abbott Vascular (approved by the FDA on 2nd July 2008) are approved in the US. Following approval of the Cypher and Taxus stents, the clinical data indicated a slightly higher incidence of stent thrombosis (ST) as compared to the pure BMS after implantation. The present article discusses the main clinical trials and design developments in DES currently available and takes a prospective look at future technologies in the field of DES.     

New developments in drug-eluting stents

Although the use of balloon catheters or stents for the treatment of coronary artery lesions shows good short-term results, long-term prognosis due to the occurrence of restenosis in 20%-30% of patients is less promising. Thus new techniques and mechanical improvements to balloons and stents are always necessary in order to achieve the best possible results from percutaneous coronary intervention. Drug-eluting stents (DES) have improved the principles of bare metal stents (BMS) by neointimal growth inhibition due to local drug release. DES can significantly reduce the incidence of in-stent restenosis. These benefits and lower costs compared to surgical treatment make the DES a more attractive alternative for the treatment of coronary heart disease. Currently, the CYPHER Sirolimus-eluting stent (SES) by Cordis (approved by the FDA on 24th April 2003), the TAXUS Express and the LIBERTE Paclitaxel-eluting stent (PES) by Boston Scientific (approved by the FDA on 4th March 2004 and October 10, 2008), the Endeavor Zotarolimus-eluting stent (ZES) by Medtronic (approved by the FDA on 1st February 2008) and the Xience V Everolimus-eluting stent (EES) by Abbott Vascular (approved by the FDA on 2nd July 2008) are approved in the US. Following approval of the Cypher and Taxus stents, the clinical data indicated a slightly higher incidence of stent thrombosis (ST) as compared to the pure BMS after implantation. The present article discusses the main clinical trials and design developments in DES currently available and takes a prospective look at future technologies in the field of DES.     

Diffuse in-stent restenosis of CYPHER? stent due to hypersensitivity reaction confirmed by pathohistological findings

The use of drug-eluting stents (DES) reduces the risk of repeat revascularization without increase of death and myocardial infarction compared to standard bare metal stents. However, in-stent restenosis (ISR) after DES implantation still occurs. Here, we report a rare case with a diffuse ISR after CYPHER^? stent implantation because of chronic inflammation and hypersensitivity reactions, confirmed by pathohistological findings.     

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.     

Significant reduction in restenosis after the use of sirolimus-eluting stents in the treatment of chronic total occlusions

OBJECTIVES: The aim of this study was to assess sirolimus-eluting stent (SES) implantation for the treatment of chronic total coronary occlusions (CTO). BACKGROUND: Long-term results after percutaneous coronary intervention (PCI) in the treatment of CTOs is hindered by a significant rate of restenosis and reocclusion. In the treatment of relatively simple nonocclusive lesions, SESs have shown dramatically reduced restenosis rates compared with bare metal stents (BMS), but whether these results are more widely applicable is unknown. METHODS: From April 2002, all patients at our institution were treated with SES as the device of choice during PCI. During the first six months, 563 patients were treated solely with SES, with treatment of a de novo CTO in 56 (9.9%). This CTO cohort was compared with a similar group of patients (n = 28) treated in the preceding six-month period with BMS. RESULTS: At one year, the cumulative survival-free of major adverse cardiac events was 96.4% in the SES group versus 82.8% in the BMS group, p < 0.05. At six-month follow-up, 33 (59%) patients in the SES group underwent angiography with a binary restenosis rate (>50% diameter stenosis) of 9.1% and in-stent late loss of 0.13 +/- 0.46 mm. One patient (3.0%) at follow-up was found to have reoccluded the target vessel. CONCLUSIONS: The use of SESs in the treatment of chronic total coronary occlusions is associated with a reduction in the rate of major adverse cardiac events and restenosis compared with BMS.     

Benefits of drug eluting stents versus bare metal stents in ST-elevation myocardial infarction: a contemporary review

The efficacy of drug-eluting stents (DES) in reducing the rates of in-stent restenosis after percutaneous coronary intervention (PCI) compared to bare metal stents (BMS) in stable coronary artery disease has been well demonstrated. Thus, the Food and Drug Administration has approved the utilization of DES for stable coronary disease. However, there is still much debate surrounding the implantation of DES for patients with ST-segment elevation myocardial infarction (STEMI) given safety concerns about the possibility of increased rates of stent thrombosis with DES. The review of the current body of evidence comparing DES with BMS is consistent with results from previous trials in stable coronary disease and reveals lower rates of revascularization with DES in STEMI patients. The ultimate decision regarding the appropriate stent during PCI needs to be individualized as patients' compliance with dual antiplatelet therapy is critical. The data suggest that PCI with DES in STEMI patients who adhere to long-term dual antiplatelet therapy is safe and effective. Randomized trials with longer-term follow-up are necessary to better elucidate the safety and efficacy of DES versus BMS in patients with STEMI.     

Drug-eluting stents show delayed healing: paclitaxel more pronounced than sirolimus.

AIMS: To understand wound healing after drug-eluting stents (DES) placement in humans, we studied the histology of in-stent restenosis (ISR) tissue obtained by atherectomy from bare metal stents (BMS) and DES in comparison with de novo atherosclerosis. METHODS AND RESULTS: The tissue was retrieved from ISR in ten sirolimus-eluting stents (SES) and nine paclitaxel-eluting stents (PES), six BMS, and nine stenotic de novo atherosclerotic lesions and processed for histology and immunocytochemistry. Patients with ISR in PES showed a significantly higher incidence of unstable angina upon presentation for re-intervention (P = 0.046). De novo tissue tended to be more collagen rich, whereas ISR tissue tended to be more proteoglycan rich. In all groups, cell content consisted almost exclusively of smooth muscle cells. Histology showed that fibrinoid in ISR tissue was present only in DES (P = 0.004), as late as 2 years following DES placement, indicating a persistent incomplete healing response. The amount of fibrinoid, given as a percentage of total tissue in each atherectomy specimen, was greater in PES than in SES (17 vs. 5%, P = 0.026). CONCLUSION: ISR in DES shows incomplete neointimal healing as late as 2 years after implantation. Patients with ISR in PES presented with more unstable angina and showed more pronounced signs of delayed healing than SES.     

Angiographic and clinical outcome for the treatment of in-stent restenosis with sirolimus-eluting stent compared to vascular brachytherapy

Summary Background With the use of coronary stents for the treatment of coronary artery disease, in-stent restenosis became a major clinical problem. In this non-randomized study, we examined the use of stent-based delivery of sirolimus (rapamycin) for the treatment of in-stent restenosis in comparison to intracoronary -brachytherapy, regarding the clinical effectiveness and the angiographic results for the treatment of in-stent restenosis after 6–9 months. Methods and results Between July 2001 and May 2002, 28 patients (65±11 years) with instent restenosis were treated with intracoronary brachytherapy. Consecutively, between May 2002 and April 2003, 28 patients (65±10 years) with in-stent restenosis were treated with the implantation of a sirolimus-eluting stent (SES). Patients with in-stent restenosis treated by implantation of a SES had significantly lower incidence of in-stent restenosis (1/28 (3.6%) vs 10/28 (36%); p=0.007) and insegment restenosis (4/28 (14%) vs 14/28 (50%); p=0.013) compared to patients treated with brachytherapy. Target lesion and target vessel revascularization rate tended to be lower in the SES group (14 vs 25%) but did not yet reach statistical significance. One patient died in the group treated by implantation of a SES eight months after stenting, one patient suffered from myocardial infarction due to a subtotal in-stent restenosis after brachytherapy. Two patients after brachytherapy underwent surgical revascularization due to recurrent in-stent restenosis similar to the patient with in-stent restenosis after SES implantation. Conclusion In this study we show the feasibility and safety of the treatment of in-stent restenosis by implantation of sirolimus-eluting stents and demonstrate a lower incidence of recurrent in-stent restenosis as well as lower late luminal loss compared to treatment by intravascular brachytherapy.

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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.     

Late restenosis following placement of a sirolimus eluting stent for in-stent restenosis

Drug eluting stents (DES) are rapidly replacing intravascular brachytherapy for the treatment of bare metal in-stent restenosis (ISR). To date, there are no long-term follow up data supporting this practise. We report symptomatic repeat in-stent restenosis occurring 27 months after sirolimus eluting stent deployment for de novo in-stent restenosis. This case suggests that in a subgroup of patients with ISR, as with brachytherapy, the drug eluting stent may be simply delaying rather than inhibiting the restenotic process.     

Effect of sirolimus-eluting stent in diabetic patients with small coronary arteries (a SES-SMART substudy)

Randomized clinical trials have shown that sirolimus-eluting stents (SESs) decrease restenosis rates compared with bare metal stents (BMSs), but their efficacy among patients who have diabetes mellitus remains to be established. This study investigated the effect of SES implantation in a high-risk population (i.e., patients who had diabetes and small coronary vessel disease). For this purpose, we analyzed outcomes of the subset of patients who had diabetes and were enrolled in the SES-SMART, a randomized trial that compared the results of implantation of SESs and BMSs in small coronary arteries. Twenty-nine patients who had diabetes were originally randomized to receive SESs and 45 patients received BMSs. The use of SESs was associated with approximately 60% decreases in the relative incidence of in-segment angiographic restenosis (63% vs 25%, p = 0.003) and in-segment late loss (0.76 vs 0.28 mm, p <0.002). Angiographic patterns of restenosis were more favorable in the SES group. SES implantation was associated with a 15% absolute decrease in adverse clinical events. In patients who had insulin-dependent diabetes mellitus, SESs showed a high in-segment restenosis rate (40%) that was principally due to persistent restenosis. In conclusion, in diabetics with small coronary arteries, SES implantation significantly reduces the incidence of the 8-month angiographic restenosis rate compared with BMSs.