Absorbierbare Stents

Coronary stent implantation started in Germany 20 years ago. In the beginning, the progress was very slow and accelerated 10 years later. Meanwhile, coronary stent implantation is a standard procedure in interventional cardiology. From the beginning of permanent stent implantation, research started to provide temporary stenting of coronary arteries, first with catheter-based systems, later with stent-alone technology. Stents were produced from polymers or metal.The first polymer stent implantation failed except the Igaki-Tamai stent in Japan. Newly developed absorbable polymer stents seem to be very promising, as intravascular ultrasound (IVUS) and optical coherence tomography have demonstrated.Temporary metal stents were developed based on iron and magnesium. Currently, the iron stent is tested in peripheral arteries. The absorbable magnesium stent (Biotronik, Berlin, Germany) was tested in peripheral arteries below the knee and meanwhile in the multicenter international PROGRESS-AMS (Clinical Performance and Angiographic Results of Coronary Stenting with Absorbable Metal Stents) study. The first magnesium stent implantation was performed on July 30, 2004 after extended experimental testing in Essen. The magnesium stent behaved like a bare-metal stent with low recoil of 5-7%. The stent struts were absorbed when tested with IVUS. Stent struts were not visible by fluoroscopy or computed tomography (CT) as well as magnetic resonance imaging (MRI). That means, that the magnesium stent is invisible and therefore CT and MRI can be used for imaging of interventions. Only using micro-CT the stent struts were visible. The absorption process could be demonstrated in a patient 18 days after implantation due to suspected acute coronary syndrome, which was excluded. IVUS showed a nice open lumen. Stent struts were no longer visible, but replaced by tissue indicating the previous stent location. Coronary angiography after 4 months showed an ischemia-driven target lesion revascularization rate of 23.8% which was below the 30% cut point of the study protocol. No myocardial Q wave infarction or death were reported. The primary endpoint was reached.During the follow-up period, vasomotion was tested in some of the patients. The proof of principle was confirmed: restoration of vasomotion during acetylcholine testing.The development of the absorbable magnesium stent, which was pushed forward by B. Heublein, Hanover, Germany, has been successful and opens new possibilities for treatment of coronary arteries. Permanent foreign-body implantation is avoided allowing further revascularization procedures in the future, bypass grafting, and restoration of vasomotion. Even prophylactic stenting in nonsignificant stenosis, like vulnerable lesions, may become a regular procedure. Noninvasive coronary imaging by CT and MRI is now possible. Stenting of children and in peripheral arteries may become a standard procedure. Currently, the degradation process of the magnesium stent has to be prolonged, and the neointima proliferation rate has to be reduced so that the DREAM (Drug-Eluting Absorbable Magnesium Stent) concept of Ron Waksman, Washington, DC, USA, can be realized.     

Enterale Stents

Stenosis of the duodenum is a common complication of malignancy of the pancreatic head or the biliary system. The resulting gastroduodenal outlet obstruction has a significant morbidity and lowers the patient’s quality of life. In addition to the palliative surgical gastroenterostomy, the endoscopic application of enteral stents has been established as a treatment. This method is efficient for symptom relief and causes few complications. There is a lack of large prospective randomized studies comparing the two methods, but the palliative endoscopic method seems to be effective and efficient, and in advanced tumor stages, probably even superior to surgical gastroenterostomy.     

Estrogen-Eluting Stents

Coronary stenting is routinely utilized to treat symptomatic obstructive coronary artery disease. However, the efficacy of bare metal coronary stents has been historically limited by restenosis, which is primarily due to excessive neointima formation. Drug-eluting stents (DES) are composed of a stainless steel backbone encompassed by a polymer in which a variety of drugs that inhibit smooth muscle cell proliferation and excessive neointima formation are incorporated. DES have significantly reduced the incidence of restenosis but are also associated with a small (~0.5% per year) but significant risk of late stent thrombosis. In that regard, estrogen-eluting stents have also undergone clinical evaluation in reducing restenosis with the additional potential benefit of enhancing reendothelialization of the stent surface to reduce stent thrombosis. Estrogen directly promotes vasodilatation, enhances endothelial healing, and prevents smooth muscle cell migration and proliferation. Due to these mechanisms, estrogen has been postulated to reduce neointimal hyperplasia without delaying endothelial healing. In animal studies, estrogen treatment was effective in decreasing neointimal hyperplasia after both balloon angioplasty and stenting regardless of the method of drug delivery. The first uncontrolled human study using estrogen-coated stents demonstrated acceptable efficacy in reducing late lumen loss. However, subsequent randomized clinical trials did not show superiority of estrogen-eluting stents over bare metal stents or DES. Further studies are required to determine optimal dose and method of estrogen delivery with coronary stenting and whether this approach will be a viable alternative to the current DES armamentarium.     

药物洗脱支架与金属裸支架内血栓发生率比较

目的:了解置入药物洗脱支架(DES)患者在经皮冠状动脉(冠脉)介入治疗(PCI)术后各期支架血栓(ST)的发生情况,并与置入金属裸支架(BMS)患者进行比较,探讨影响支架血栓发生的危险因素.方法:连续入选2001-07至2002-06和2003-07至2005-06期间接受PCI并置入支架的所有患者,共入选3 893例.随访至少2年.根据所使用支架分为DES组(n=2 930,至少置入1枚DES)和BMS组(n=963,单纯置入BMS).记录所有患者住院期和随访期内临床资料,并根据美国和欧洲学者组成的学术研究联盟(ARC)正式发表的支架血栓定义判定支架血栓事件.结果:与BMS组相比,DES组患者的平均年龄较大,而白细胞数、甘油三脂水平和空腹血糖水平较低,既往有冠脉血运重建病史者较多,但吸烟、糖尿病和ST段抬高型心肌梗死(STEMI)发生率较低;在DES组患者的冠脉病变中,多支病变、开口病变、前降支(LAD)近段病变和左主干(LM)病变发生率较高,但慢性完全闭塞性(CTO)病变所占的发生率较低,造影成功率及完全血运重建率均较高,差异均有统计学意义(P均＜0.05～0.001).两组患者PCI术后无论在住院期还是之后的随访期内,所有的不良心脑血管事件发生率均无显著差异,而支架血栓发生率在急性期、亚急性期、晚期和晚晚期均无差异(P均＞0.05).Cox回归分析结果提示,DES组患者发生支架血栓的危险因素为:氯吡格雷疗程短和冠脉多支病变(P均＜0.001);而BMS组患者发生支架血栓的危险因素为:血清肌酐值升高和合并高血压(P均＜0.05).结论:尽管DES时代患者的病变更为复杂,所置入的DES数更多,但支架血栓的发生率并不比BMS时代更高.但术后双联抗血小板治疗的疗程过短和冠脉多支病变是支架血栓发生的危险因素,应引起重视.     

Biodegradable Polymeric Stents

To overcome several problems of conventional metallic stents, there have been many attempts to manufacture stents made of biodegradable materials. Although some studies have noted various degrees of inflammatory responses after biodegradable stent implantation, stents made of poly-l-lactic acid (PLLA) showed high biocompatibility with minimal inflammatory response and neointimal formation in porcine coronary arteries. Therefore, PLLA materials are more likely to cover the specific need for human coronary arteries in terms of biodegradation period and scaffolding ability over 6 months. A clinical study of PLLA self-expanding stent implantation is underway in Japan. The initial and 6-month results are favorable and suggest the feasibility, safety, and efficacy of the PLLA biodegradable stent in humans. However, long-term follow-up with larger numbers of patients will be required to validate the long-term efficacy of PLLA stents.     

新型药物支架

药物支架治疗冠状动脉性心脏病在临床上已经取得了良好的效果。然而,支架术后血栓问题困扰着人们。新型药物支架的研发不断进行,现分别对选用不同支架材料、药物载体、涂层药物及药物释放方式的新型药物支架的研究进展进行综述。     

Heparin-Coated Coronary Stents

The development of the heparin-coated (HC)-stent should be viewed against the backdrop of the early unfavorable results with noncoated stents in the pre-intravascular ultrasound and pre-ticlopidine era. Notwithstanding, results of pilot and randomized trials show a surprisingly low incidence of (sub)acute stent thrombosis under challenging circumstances, such as acute coronary syndromes. Considering the quite low incidence of early complications with noncoated second-generation stents, it may require large trials to prove the clinical efficacy of the heparin- coating against noncoated devices. However, even if the "added value" of the heparin-coating will never be clinically proven, it has helped to enhance the penetration of stent therapy in interventional cardiology. Unlike the situation in 1992, very few cardiologists will now disagree with the statement that stents contribute to the state-of-the-art treatment of patients with angina pectoris or acute myocardial infarction. A preliminary comparison of available trials also suggests that the heparin-coated Palmaz-Schatz stent (Cordis Corp., Waterloo, Belgium) is as effective as the noncoated stent plus abciximab treatment.     

Sirolimus-Eluting Stents versus Paclitaxel-Eluting Stents in Patients with Chronic Renal Insufficiency

Background: Chronic renal insufficiency (CRI) is associated with an increased incidence of restenosis and stent thrombosis. Drug-eluting stents (DES), when compared to bare metal stents (BMS), reduce the incidence of restenosis in these patients. This study aimed to examine whether there are differences in clinical outcome after implantation of sirolimus-eluting stents (SES) versus paclitaxel-eluting stents (PES) in patients with CRI who are subjected to coronary intervention.
Methods: A cohort of 570 patients with CRI who underwent intervention with DES (346 with SES and 224 with PES) were followed clinically up to 1 year and the clinical events were recorded and compared between groups.
Results: Baseline and procedural characteristics were similar, with a slightly higher number of diseased vessels in the SES group as compared to the PES group (2.3 ± 0.9 vs 2.1 ± 0.9, P = 0.06). The overall rates of major adverse cardiac events (MACE) and stent thrombosis were similar. The PES group had lower revascularization rates when compared to the SES group. After covariate adjustment, however, there was no difference seen in target vessel revascularization between stent types (hazard ratio [HR]: 2.3 [0.8–6.2], P = 0.110). The strongest predictor of death and MACE at 1 year was the number of diseased vessels.
Conclusions: Patients with CRI who undergo PCI with either SES or PES have similar repeat revascularization rates and acceptable stent thrombosis rates, although they continue to have high MACE and death rates. (J Interven Cardiol 2010;23:33–39)     

Comprehensive Meta-Analysis on Drug-Eluting Stents versus Bare-Metal Stents during Extended Follow-up

Background

Several observational reports have documented both increased and decreased cardiac mortality or Q-wave myocardial infarction with drug-eluting stents compared with bare-metal stents.

Methods

We sought to evaluate the safety and efficacy of drug-eluting stents compared with bare-metal stents early after intervention (<1 year) and late (>1 year) among a broad population of patients, using a meta-analysis of randomized clinical trials.

Results

We identified 28 trials with a total of 10,727 patients and a mean follow-up of 29.6 months. For early outcomes (<1 year), all-cause mortality for drug-eluting stents versus bare-metal stents was 2.1% versus 2.4% (risk ratio [RR] 0.91, [95% confidence interval (CI), 0.70-1.18]; P = .47), non-Q-wave myocardial infarction was 3.3% versus 4.4% (RR 0.78 [95% CI, 0.61-1.00]; P = .055), target lesion revascularization was 5.8% versus 18.4% (RR 0.28 [95% CI, 0.21-0.38]; P <.001), and stent thrombosis was 1.1% versus 1.3% (RR 0.87 [95% CI, 0.60-1.26]; P = .47). For late outcomes (>1 year), all-cause mortality for drug-eluting stents versus bare-metal stents was 5.9% versus 5.7% (RR 1.03 [95% CI, 0.83-1.28]; P = .79), target lesion revascularization was 4.0% versus 3.3% (RR 1.22 [95% CI, 0.92-1.60]; P = .16), non-Q-wave myocardial infarction was 1.6% versus 1.2% (RR 1.36 [95% CI, 0.74-2.53]; P = .32) and stent thrombosis was 0.7% versus 0.1% (RR 4.57 [95% CI, 1.54-13.57]; P = .006).

Conclusions

There was no excess mortality with drug-eluting stents. Within 1 year, drug-eluting stents appear to be safe and efficacious with possibly decreased non-Q-wave myocardial infarction compared with bare-metal stents. After 1 year, drug-eluting stents still have similar mortality, despite increased stent thrombosis. The reduction in target lesion revascularization with drug-eluting stents mainly happens within 1 year, but is sustained thereafter.     

Polymer-Free Biolimus-Eluting Stents or Polymer-Based Zotarolimus-Eluting Stents for Coronary Bifurcation Lesions

BackgroundA polymer-free biolimus-eluting stent (PF-BES) and a zotarolimus-eluting stent (ZES) recently showed similar clinical profiles and appear to be competing options in specific clinical settings of patients undergoing percutaneous coronary intervention (PCI). Whether they perform similarly also in complex procedural settings as coronary bifurcation lesions remains unaddressed.MethodsAll consecutive patients undergoing coronary bifurcation PCI with PF-BES or the new iteration of the ZES from three large multicenter real-world registries were included. The primary outcome was major adverse cardiovascular events (MACE), a composite of all-cause death, myocardial infarction (MI), target lesion revascularization (TLR) and stent thrombosis (ST). Multiple analyses to adjust for baseline differences were carried out including propensity-score matching, propensity-score stratification and inverse-probability-weighting. Outcomes are reported according to Cox proportional hazard models censored at 400-day follow-up.Results1169 patients treated with PF-BES (n = 440) or ZES (n = 729) on the main branch of a coronary bifurcation lesion were included (mean age 69 ± 11 years, 75.4% male, 53.8% acute coronary syndrome at presentation, 26.6% left main bifurcation, median dual antiplatelet therapy duration 12 [range 12–12] months). MACE, all-cause death, TLR and ST tended towards non-statistically higher rates with the PF-BES as compared to the ZES. Higher MI and target vessel revascularization occurrence was observed with PF-BES.ConclusionsIn this large contemporary cohort of patients undergoing coronary bifurcation PCI, the occurrence of MACE was non-statistically different with the use of PF-BES and ZES devices. However, differences favoring the ZES device that may entail clinical relevance were observed. Further studies are needed to confirm these findings and explore whether they remain valid when a short dual antiplatelet therapy is adopted.     

Drug-Eluting Stents Versus Bare-Metal Stents in Patients With End-Stage Renal Disease

Background

The clinical outcomes of drug-eluting stents versus bare-metal stents in end-stage renal disease patients remains controversial.

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.