Drug-eluting stents for the treatment of in-stent restenosis: A clinical review

Treatment of in-stent restenosis (ISR) remains problematic despite the widespread application of drug-eluting stents (DES). Challenging lesion cohorts such as diffuse ISR and restenosis after failed intracoronary radiation therapy (IRT) maybe best treated with DES. The overall benefit of DES appears inferior to their utility in treating de novo coronary lesions. Randomised trials comparing DES and IRT will soon be available to determine the optimal therapy for ISR. The challenge to treat ISR in the DES era is the next frontier of interventional cardiology.     

Drug-eluting stents or balloon angioplasty for drug-eluting stent-associated restenosis: An observational follow-up study of first-time versus repeated restenosis

Background

The treatment of patients with repeated drug-eluting stent–in stent restenosis (DES-ISR) remains a challenge and a burdensome clinical problem.

不同药物洗脱支架四年临床结果比较

目的 观察雷帕霉素与紫杉醇药物洗脱支架(DES)置入后再狭窄率、支架内血栓形成及4年临床结果.方法 回顾性分析2003年1-10月连续237例置入DES患者6个月再狭窄率与靶病变重建率(TLR)、4年随访主要不良心脏事件(MACE)、靶血管重建(TVR)和支架血栓形成的发生率.结果 雷帕霉素组与紫杉醇组比较,6个月两组TLR、支架内再狭窄、MACE、心肌梗死差异均无统计学意义,但后者有更高的晚期管腔丢失(P=0.022).4年免于TVR生存率分别为88.97%与82.28%(P=0.127),免于MACE生存率分别为83.8%与79.2%(P=0.056).多变量分析每个病变置入支架数(P=0.001)和糖尿病(P=0.001)与TVR相关,多支病变(P=0.0013)和糖尿病(P:0.0001)与MACE相关.4年总的支架内血栓发生率(1.47%与1.98%)无统计学意义,肯定的很可能的和可能的支架内血栓形成两组之间也无统计学意义(P>0.05).结论 两种药物洗脱支架均具有较好的安全性和临床近、远期效果,但紫杉醇洗脱支架晚期管腔丢失较多.     

西罗莫司和紫杉醇洗脱支架治疗支架内再狭窄的临床近期及10个月疗效

目的比较西罗莫司洗脱支架（Cypher或Cypher select）和紫杉醇洗脱支架（TAXUS）治疗支架内再狭窄的临床近期及10个月疗效。方法自2002年12月至2005年3月,对253例支架内再狭窄的患者采用了药物洗脱支架（DES）治疗并完成了10个月的临床随访和冠状动脉造影复查。253例中男性218例,女性35例,年龄30～80岁,平均年龄57．2岁。结果253例（262处病变）中152例使用Cypher支架176个,101例使用TAXUS支架132个。使用的Cypher和TAXUS支架的平均直径分别为（2．96±0．27）mm和（3．05±0,35）mm,P=0．04,平均长度分别为（23.31±6．68）mm和（23．56±6．54）mm,P=0．745。支架内再狭窄表现为100％闭塞29处,≥90％狭窄143处,〈90％狭窄90处。病变类型为A、B1、B2和C型各为9处、45处、73处和135处。PCI的成功率两组均为100％,住院期间无死亡,Cypher组主要心脏不良事件（MACE）发生率为2．63％,TAXUS组为2．97％,P=0．872。10个月临床造影显示在Cypher支架和TAXUS支架组中造影再狭窄率分别为14．0％和29．4％,P=0．075,MACE发生率分别为6．7％和16．0％,P=0．031。结论应用Cypher和TAXUS支架治疗支架内再狭窄有良好的近期临床疗效,10个月疗效Cypher支架优于TAXUS支架。     

Four-year results after brachytherapy for diffuse coronary in-stent restenosis: will coronary radiation therapy survive?

BACKGROUND: Prior to the introduction of drug-eluting stents (DES), diffuse coronary in-stent restenosis (ISR) was mainly treated by brachytherapy (BT), with good short-term and mid-term results. However, there exist limited data on the long-term effects of BT that justify its continuous use. MATERIALS AND METHODS: Two hundred patients with diffuse ISR treated with intravascular BT were retrospectively followed over 4 years. Group A (n=134) was treated with the noncentered (90)Sr/Y BetaCath radiation system, whereas Group B (n=66) was treated with the centered 32P Galileo source wire system. Primary endpoints after 4 years were target lesion restenosis (TLS) and target lesion revascularization (TLR). Secondary endpoints were target vessel revascularization (TVR) and nontarget vessel revascularization (NTVR), as well as major adverse cardiac events (MACE). RESULTS: Follow-up at 4 years yielded a TLS rate of 37.6% (Group A, 40.8%; Group B, 31.1%; P=.48). TLR was performed in 34.8% of patients (37.5% in Group A vs. 29.5% in Group B; P=.55). Ten percent of patients underwent coronary bypass surgery. Percutaneous coronary intervention was performed more often in Group A (27.5%) than in Group B (19.7%), while TVR was less frequent in Group A (10.0%) than in Group B (18.0%). NTVR was undertaken in 25.0% of Group A patients versus 21.3% of Group B patients, and MACE occurred in 1.7% of Group A patients versus 3.3% of Group B patients. These differences were not statistically significant (P>.05). CONCLUSIONS: While excellent short-term and mid-term results after coronary BT are widely accepted, a high TLS rate can be observed after 4 years. The potential superiority of DES to BT will depend on the availability of long-term clinical data.     

Treatment of coronary in-stent restenosis: a systematic review

Coronary stent implantation has significantly improved percutaneous coronary intervention and enabled the management of early complications of plain balloon angioplasty. However, a new complication has accompanied these improvements: in-stent restenosis (ISR) arising from neointimal hyperplasia. ISR after coronary angioplasty is currently one of the main limitations of this method, leading to the recurrence of exertional angina pectoris or acute coronary syndromes. The clinical incidence of ISR after bare-metal stent (BMS) implantation is approximately 20%–35%. The use of drug-eluting stents (DES) has led to a further decrease in the occurrence of ISR to 5%–10%. Evidence resulting from controlled clinical studies suggests that DES and drug-eluting balloon catheters (DEB) provide the best clinical and angiographic results in the treatment of ISR. We undertook a systematic review of the pathophysiology, diagnostics and treatment options for BMS- and DES-ISR. We discuss recent randomised studies, comparing different DES or DEB used for BMS or DES-ISR treatment, as well as the use of new biovascular scafolds and the topic of scafold restenosis.     

What is the best contemporary treatment for in-stent restenosis?

In-stent restenosis (ISR) remains a challenging problem in percutaneous coronary intervention and the optimal treatment strategy remains unclear. The aim of this study was to compare the 18 month clinical outcomes in patients receiving sirolimus-eluting stents (SES) with vascular brachytherapy (VBT) for the treatment of ISR. Twenty-five consecutive patients treated with VBT were compared with 29 patients who had SES deployment for ISR. Major adverse cardiac events (MACE) were defined as a combination of death from cardiac causes, nonfatal myocardial infarction, or repeat TVR. At 18 month follow-up, the MACE rate was significantly lower in the SES compared with the VBT group (14% vs 40%, P=.03). One patient in the VBT group developed late stent thrombosis (at 10 months) and died; there was no stent thrombosis in the SES group. This observational study, taken with other recent reports, offers further credence to the use of SES for ISR. The results of randomized comparisons with VBT are awaited with interest.     

Incidence and predictors of recurrent restenosis following implantation of drug-eluting stents for in-stent restenosis.

OBJECTIVES: We investigated the incidence and predictors of recurrent restenosis after drug-eluting stent (DES) implantation for in-stent restenosis (ISR) in routine clinical practice. BACKGROUND: Although DESs have been increasingly used for treatment of ISR, little is known about the predictors of DES failure. METHODS: We determined the incidence of recurrent restenosis and major adverse cardiac events (MACE) in 224 consecutive patients with 239 lesions treated with sirolimus-eluting (n=217 lesions) or paclitaxel-eluting (n=22 lesions) stents for the first episode of ISR. RESULTS: The procedural success rate was 99.2%, and in-hospital complications did not occur in any patient. Follow-up angiography at 6 months was obtained in 73.7% of patients. Angiographic re-restenosis rate was 12.6%, and target lesion revascularization was required in 7.6% of patients. Of the 22 incidents of re-restenosis, 15 were focal (68.2%), 5 were diffuse (22.7%), and 2 were total (9.1%) restenosis. Univariate analysis showed that lesion length, use of paclitaxel-eluting stent, and number of stents per lesion were significant predictors of re-restenosis. In multivariate analysis, however, lesion length and use of paclitaxel-eluting stent were independent predictors of re-restenosis. During the follow-up (mean, 18.3+/-8.1 months), there were 4 deaths (1 cardiac, 3 noncardiac), but no nonfatal myocardial infarctions (MIs). MACE occurred in 18 patients. The cumulative probability of MACE-free survival was 92.9+/-1.8% at 1 year and 90.5+/-2.4% at 2 years. CONCLUSIONS: DESs are highly effective for treatment of ISR, with recurrent restenosis related to lesion length and type of DES.     

Bioresorbable vascular scaffold for coronary in-stent restenosis: A novel concept

The management of patients with significant in-stent restenosis (ISR) with drug-eluting stent is still not well defined. Various treatment modalities include plain old balloon angioplasty (POBA), metallic stent, cutting or scoring balloon and drug-eluting balloon (DEB). Bioresorbable vascular scaffold (BVS) is the latest technology for the treatment of de novo coronary artery lesions. The use of BVS in ISR is based on the rationale of local drug delivery as achieved by DEB without the permanent bi-layer of metal and also stabilizes dissection flaps and prevents acute recoil as provided by metallic stent. To the best of our knowledge this is the first case report of the use of BVS in patient with ISR.     

Influence of increased epicardial adipose tissue volume on 1-year in-stent restenosis in patients who received coronary stent implantation

Background Epicardial adipose tissue (EAT) is significantly associated with the formation and composition of coronary atherosclerotic plaque, cardiac events and the clinical prognosis of coronary heart disease. But, whether increased EAT deposition may affect the incidence of in-stent restenosis (ISR) is currently unclear. This study used coronary computed tomography angiography (CCTA) as a mean to investigate whether increased EAT volume was associated with ISR. Methods A total of 364 patients who underwent 64-slice CCTA examination for the evaluation of suspected coronary artery disease, and subsequently underwent percutaneous coronary intervention (PCI) for the first time, and then accepted coronary angiography (CA) follow-up for ISR examination in one year, were retrospectively included in this study. EAT volume was measured by CCTA examination. CA follow-up was obtained between 9 and 15 months. ISR was de?ned as ≥ 50% luminal diameter narrowing of the stent segment or peri-stent segment. EAT volume was compared between patients with and without ISR and additional well-known predictors of ISR were compared. Results EAT volume was signi?cantly increased in patients with ISR compared with those without ISR (154.5 ± 74.6 mL vs. 131.0 ± 52.2 mL, P < 0.001). The relation between ISR and EAT volume remained signi?cant after adjustment for conventional cardiovascular risk factors and angiographic parameters. Conclusions EAT volume was related with ISR and may provide additional information for future ISR.     

Drug-eluting stents compared with thin-strut bare stents for the reduction of restenosis: a prospective, randomized trial.

AIM: Drug-eluting stents have considerably reduced restenosis. Their relative merits have been assessed on the basis of comparisons made with control bare stents with thick struts. However, increased strut thickness negatively affects restenosis. No direct comparisons between drug-eluting stents and bare stents with thin struts have been performed. The aim of this study was to evaluate the relative efficacy of sirolimus-eluting stents (Cypher) as compared with that of bare stents with thin struts (BeStent 2). METHODS AND RESULTS: A total of 500 patients with coronary artery disease were randomly assigned to receive a Cypher stent or BeStent. The primary endpoint was angiographic restenosis defined as a stenosis diameter > or = 50% at 6-month angiographic follow-up. The secondary endpoint was the need for target vessel revascularization (TVR) during the year following the procedure. Follow-up angiography was performed in 81.8% of the patients. Patients treated with Cypher stents had a lower angiographic restenosis rate [8.3 vs. 25.5%, relative risk, 0.33 (95% confidence interval, 0.19-0.56), P<0.001] and a lower incidence of TVR [7.2 vs. 18.8%, relative risk, 0.38 (0.22-0.66), P<0.001]. For smaller vessels (< 2.8 mm), the angiographic restenosis rates were 7.0% with the Cypher stent and 34.2% with the BeStent (P<0.001). For larger vessels (> or = 2.8 mm), angiographic restenosis rates were 10.0% with the Cypher stent and 13.1% with the BeStent (P=0.52). CONCLUSION: The drug-eluting stent, Cypher, is associated with a significantly lower risk of restenosis compared with the bare thin-strut BeStent. The advantage of the Cypher stent is vastly reduced in large vessels.     

A comparative study of restenosis rates in bare metal and drug-eluting stents

BACKGROUND:

Various studies have been performed throughout the world on the rate of restenosis using bare metal stents (BMS) and drug-eluting stents (DES). The prohibitive costs associated with DES generally dictate the type of stent used, especially in developing countries. Therefore, there was a need for a study to assess the effect of various risk factors on restenosis in BMS and DES in the Indian context. A study was performed in the premier institution of the Indian Armed Forces, the Army Hospital (Research and Referral), New Delhi, India, under the aegis of the Indian Council of Medical Research (New Delhi). The profile of patients in the armed forces is inherently diverse in terms of demography, ethnicity, genetics, etc, which reflects the diverse and varied nature of the population in India.

METHODS AND RESULTS:

A total of 130 patients were included in the present study. Follow-up after stent implantation was scheduled for six to nine months following the procedure to assess symptoms, drug compliance, and treadmill test and coronary angiography results, and to ascertain the incidence of restenosis. However, only 80 patients returned for follow-up and, therefore, the final analysis was based on these patients. They were segregated into BMS (n=41) and DES (n=39) groups. Restenosis occurred in 29 patients (36.3%). Nine of 39 patients with DES (23.1%) and 20 of 41 patients with BMS (48.8%) developed restenosis. There was a statistically significant relationship between restenosis and female sex, clinical presentation before intervention and at the time of follow-up evaluation (unstable angina), hypertension, positive stress test and compliance with medical therapy (P<0.05). No statistically significant relationship was observed between restenosis and age, diabetes, smoking, obesity and diet (P>0.05).

CONCLUSIONS:

DES appear to reduce the restenosis rate and clinical end points, and appear to be more cost effective than BMS. Patient-related factors (eg, sex, hypertension and unstable angina) are important variables that affect the restenosis rate. Noninvasive stress testing had high positive and negative predictive values. Therefore, based on the present study, noninvasive stress testing is suggested before routine angiography at follow-up, which will reduce the need for repeat coronary angiography.     

药物洗脱支架2年内再狭窄危险因素分析和Nomogram构建

目的探讨冠心病合并2型糖尿病患者药物洗脱支架(DES)植入后2年内再狭窄(ISR)危险因素并构建Nomogram模型。方法回顾性分析2010年1月—2020年2月在中国医学科学院阜外医院深圳医院植入DES的冠心病合并2型糖尿病患者临床资料。PASS估计模型产生队列样本量,根据冠状动脉造影结果分为支架内再狭窄组(DES-ISR)及非狭窄组(non-DES-ISR),对两组之间差异有统计学意义的参数进行单因素和条件性多因素Logistic回归分析构建Nomogram并在验证队列中验证其检验效能。结果模型产生队列共1741例,233例(13.4%)在植入DES后2年内确诊ISR,条件性多因素Logistic回归分析显示,DES-ISR的预测因素为肾小球滤过率(eGFR)<60 mL/(min·1.73 m²)(OR=2.77,95%CI:1.41~5.47,P=0.003)、血脂异常(OR=1.90,95%CI:1.30~2.78,P=0.001)、空腹血糖(FPG)≥6.5 mmol/L(OR=5.50,95%CI:3.05~9.92,P<0.001)、冠状动脉多支病变(OR=7.26,95%CI:3.27~16.11,P<0.001)、冠状动脉弥漫病变(OR=1.80,95%CI:1.13~2.88,P=0.014)、首次PCI操作时间≥60 min(OR=2.62,95%CI:1.13~6.05,P=0.024)和首次PCI为急诊(OR=2.20,95%CI:1.48~3.28,P<0.001)。模型验证队列102例,DES-ISR发生风险随Nomogram评分增高而增加,Nomogram模型受试者工作特征(ROC)曲线下面积为0.791(95%CI:0.753~0.829,P=0.019)。结论冠状动脉病变特征以及PCI操作程序是DES-ISR的重要预测因素,Nomogram能够较好地识别DES-ISR高危人群,能够为高危人群的随访干预提供有效的决策信息。     

Late thrombosis of drug-eluting stents: a meta-analysis of randomized clinical trials

Purpose

Drug-eluting stents are commonly used for percutaneous coronary intervention. Despite excellent clinical efficacy, the association between drug-eluting stents and the risk for late thrombosis remains imprecisely defined.

Methods

We performed a meta-analysis on 14 contemporary clinical trials that randomized 6675 patients to drug-eluting stents (paclitaxel or sirolimus) compared with bare metal stents. Eight of these trials have reported more than a year of clinical follow-up.

Results

The incidence of very late thrombosis (>1 year after the index procedure) was 5.0 events per 1000 drug-eluting stent patients, with no events in bare metal stent patients (risk ratio [RR] = 5.02, 95% confidence interval [CI], 1.29 to 19.52, P = .02). Among sirolimus trials, the incidence of very late thrombosis was 3.6 events per 1000 sirolimus stent patients, with no events in bare metal stent patients (RR = 3.99, 95% CI, .45 to 35.62, P = .22). The median time of late sirolimus stent thrombosis was 15.5 months, whereas with bare metal stents it was 4 months. Among paclitaxel trials, the incidence of very late thrombosis was 5.9 events per 1000 paclitaxel stent patients, with no events in bare metal stent patients (RR = 5.72, 95% CI, 1.08 to 32.45, P = .049). The median time of late paclitaxel stent thrombosis was 18 months, whereas it was 3.5 months in bare metal stent patients.

Conclusions

Although the incidence of very late stent thrombosis more than 1 year after coronary revascularization is low, drug-eluting stents appear to increase the risk for late thrombosis. Although more of this risk was seen with paclitaxel stents, it remains possible that sirolimus stents similarly increase the risk for late thrombosis compared with bare metal stents.     

Sirolimus- and paclitaxel-eluting stents in comparison with balloon angioplasty for treatment of in-stent restenosis.

This study evaluated the acute and follow-up effectiveness of sirolimus-eluting stents (SESs) and nonpolymer-based paclitaxel-eluting stents (PESs) in comparison will balloon angioplasty for treatment of complex in-stent restenosis (ISR) lesions. Drug-eluting stents have been demonstrated to be highly effective for treatment of de novo lesions. The use of drug-eluting stents for treatment of complex ISR is less well defined. Eighty one lesions with in-stent restenosis (lesion length < 30 mm in a native coronary artery) were treated with either PTCA alone (n = 26 lesions in 25 patients), PES (n = 27 lesions in 24 patients; Achieve, Cook; 3,1 mug paclitaxel/mm(2) nonpolymer-based coating), SES (n = 28 lesions in 28 patients; Cypher, Cordis; 140 mug sirolimus/cm(2) metal surface area). Nine-month MACE rates were 32%, 8%, and 14% (all due to repeated revascularization procedures, except one death in the SES group) in the PTCA, PES, and SES group, respectively. Postintervention minimal lumen diameter in stent was significantly greater in the SES and the PES group in comparison with the PTCA group (2.37 +/- 0.26, 2.54 +/- 0.42, 1.78 +/- 0.23 mm; P < 0.001). At 6-month angiographic follow-up, late loss in stent was 0.77 +/- 0.45, 0.43 +/- 0.53, and 0.29 +/- 0.52 mm for the PTCA, PES, and SES group, respectively (P = 0.005). In-lesion restenosis rate was 61% for the PTCA group, 20% for the PES group, and 13% for the SES group (P = 0.042). The implantation of SES as well as nonpolymer PES proved to be effective for treatment of ISR. The combination of improved acute gain and reduced late loss results in a significantly improved angiographic follow-up result in comparison with PTCA.     

Outcomes of stenting with overlapping drug-eluting stents versus overlapping drug-eluting and bare-metal stents for the treatment of diffuse coronary lesions

Introduction

We investigated the outcomes of stenting with overlapping drug-eluting stents (DES) versus overlapping stenting with a combination of drug-eluting and bare metal stents (BMS) in very long ≥(≥ 25 mm).

Methods and Results

Fifty-two patients treated with either overlapping DES-DES (n = 22) or DES-BMS (n = 30) were selected from a registry of 588 patients with very long coronary lesions. Patients with acute myocardial infarction (MI) within the preceding 48 hours were excluded. The DES-DES combination was more frequently used for longer lesions compared with the DES-BMS group (47.95 ± 9.25 vs 39.98 ± 9.15 mm, p = 0.003). Left anterior descending artery lesions were also more frequently treated with the DES-DES combination (95.5 vs 66.7%, p = 0.02). In four patients in the DES-BMS group, overlapping stents were used for the coverage of dissections. Peri-procedural non-Q-wave MI occurred in one patient in the DES-BMS group. On follow up, only one case of non-fatal MI occurred in a patient with overlapping DES-DES.

Conclusion

Overlapping a BMS in the proximal part of a long DES instead of exclusive deployment of two or more overlapped DES seems to be a safe and feasible therapeutic strategy in our practice.     

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.