Six-month clinical outcomes of drug eluting stents in patients with coronary artery disease: an experience in real-world Indian patients

Background: Treatment of patients with coronary artery disease using drug eluting stents (DES) remains a challenge due to stent thrombosis and in-stent restenosis. The present study sought to investigate the safety and clinical performance of DES in real-world Indian patients with coronary artery disease.Methods: This prospective, non-randomized, single-center study enrolled 114 patients with coronary artery disease who were implanted with DES from January-2005 to September-2007. Clinical and angiographic follow-up were performed at 6 months after the index procedure. The primary endpoints of the study were: (major adverse cardiac events (MACE) defined as a composite of any episode of rest angina, myocardial infarctions (MI), repeat percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG), or (angiographic restenosis defined as ≥50% diameter stenosis at the treated site at 6-month follow-up. The secondary endpoints of the study were occurrence of any MACE events and stent vessel occlusion during the first 30 postprocedural days.Results: A total of 125 lesions were treated by implantation of 130 DES. Only one patient (0.9%) developed minor bleeding during hospitalization. At the 6-month follow-up, MACE was 10%, including 1 (1.3%) MI, 2 (2.5%) unstable angina, 3 (3.8%) stable angina, 1 (1.3%) repeat PCI, and 1 (1.3%) CABG. Angiographic restenosis was found in 7 (8.8%) patients. Comparison of characteristics between patients with and without angiographic restenosis revealed significant effects of presence of diabetes (p<0.012), hyperlipidaemia (p<0.028), and stent length>20 mm (p<0.05).Conclusions: The study results demonstrated excellent safety and clinical performance of DES in real-world Indian patients with coronary artery disease.

The Bioengineered Combo Dual-Therapy CD34 Antibody-Covered Sirolimus-Eluting Coronary Stent in Patients with Chronic Total Occlusion Evaluated by Clinical Outcome and Optical Coherence Tomography Imaging Analysis

We sought to determine the effects of the use of a Bioengineered Combo Dual-Therapy CD34 Antibody-Covered Sirolimus-Eluting Coronary Stent (Combo® DTS) in patients with chronic total occlusion (CTO) by evaluating clinical outcomes and by performing an optical coherence tomography (OCT) analysis. We retrospectively analyzed data from 39 patients who had successfully undergone OCT-guided revascularization of a CTO being treated with a Combo® DTS. Clinical assessment, angiography (with quantitative coronary angiography analysis) and OCT examination were performed at baseline and at follow-up. The median follow-up period was 189 days, ranging from 157 to 615 days. At follow-up, revascularization was required due to angiographic restenosis in 40% (14 of 35) of patients. OCT analysis detected neointima proliferation in 23 (76.6%) patients. Neointima formation was often associated with microvessels in 18 patients (60%). Neoatheroslcerosis was observed in 2 (6.6%) patients. Malapposition was found in 4 patients (13.3%), and stent fractures were found in 11 patients (36.6%). Rate of strut coverage was 96.3% at follow-up. In conclusion, the implantation of a Combo® DTS after successful CTO recanalization was associated with a restenosis rate of 40% despite good stent implantation at baseline, proven by OCT. Neointima formation was found as a main contributor to restenosis. Nevertheless, we observed a low rate of major cardiovascular events in our follow-up.

Safety and feasibility of bioabsorbable everolimus-eluting stents for patients with internal pudendal artery-related arteriogenic erectile dysfunction (PERFECT-ABSORB)

Background Obstructive pelvic arterial lesions are present in ∼70% of patients aged &gt;50 years and having erectile dysfunction. The internal pudendal artery, with an average diameter of 2.5 mm, is the segment where ∼40% of pelvic obstructive lesions are located. Our prior experience showed a 40–50% binary restenosis rate for drug-eluting stents in internal pudendal artery. In this PERFECT-ABSORB study, we would like to assess the feasibility and safety of the bioresorbable everolimus-eluting vascular scaffolds (BVS), facilitated by intravascular optical coherence tomography (OCT), in patients with erectile dysfunction and concomitant internal pudendal artery stenoses. Methods This prospective, unblinded, single-arm, single-center study was a first-in-man proof-of-concept study. Patients with erectile dysfunction and obstructive pelvic arterial lesions (unilateral diameter stenosis ≥70% or bilateral stenoses ≥50%) in the internal pudendal arteries with reference vessel diameter ≥2.5 mm and ≤4.0 mm and a target-lesion length ≤30 mm in the pelvic computed tomographic (CT) angiography were recruited. All subjects underwent pelvic CT angiography, penile Doppler ultrasonography, and invasive pelvic angiography with OCT at baseline and 8 months after intervention. The primary endpoint is CT angiographic binary restenosis (≥50% lumen diameter stenosis) at 8 months. The secondary endpoints include sustained clinical success in erectile function (International Index for Erectile Function-5 [IIEF-5] score ≥22 or change in IIEF-5 ≥4 and without a later decline by ≥4) at 12 months. Results Eighteen patients were enrolled (mean age, 61.8±5.6 years; range, 52–71 years). The IIEF-5 score at baseline was 7.3±3.6, with a median duration of erectile dysfunction of 3 years. A total of 31 BVSs were implanted: seven patients were treated with one BVS, 9 patients with 2 BVSs, and 2 patients with 3 BVSs. All implanted BVSs were of 2.5 mm in diameter. Among the 17 patients undergoing 8-month follow-up pelvic CT angiography and invasive angiography (one not done due to colon cancer diagnosed later), binary CT angiographic restenosis developed in 7 (37%) of 19 lesions and 7 (41%) of 17 patients. After excluding those with lesions &gt;30 mm (per-protocol analysis), binary CT angiographic restenosis developed in 5 (31%) of 16 lesions and 5 (36%) of 14 patients. Binary restenosis assessed by invasive angiography and OCT was the same as assessed by pelvic CT angiography. Among the 17 patients, 9 (53%) achieved sustained clinical success in erectile function 12 months following the procedure. All of them did not develop binary restenosis. Conclusions We for the first time demonstrated that BVS+OCT strategy for internal pudendal artery stenosis was safe and able to achieve 30% restenosis rate in lesions ≤30 mm in length. Compared to our prior experience, BVS+OCT strategy was associated with a numerically lower restenosis rate. Funding Acknowledgement Type of funding source: None

Angiographic Restenosis in Coronary Bifurcations Treatment with Regular Drug Eluting Stents and Dedicated Bifurcation Drug-Eluting BiOSS Stents: Analysis Based on Randomized POLBOS I and POLBOS II Studies

Aim. The marked variation in bifurcation anatomy has brought about an ongoing search for stents specifically constructed for coronary bifurcations. This study aimed to analyze the angiographic restenosis prevalence and patterns and predictors of different patterns in dedicated bifurcation BiOSS® vs. current generation drug-eluting stents implanted in coronary bifurcation lesions based on data from two clinical trials POLBOS I and II. Methods. Dedicated bifurcation BiOSS® stents were compared with drug-eluting stents (DES) in patients with stable coronary artery disease (CAD) or nonST elevation acute coronary syndrome (NSTE-ACS) (POLBOS I: paclitaxel eluting BiOSS® Expert vs. DES; POLBOS II: sirolimus eluting BiOSS® LIM vs. DES). Provisional T-stenting was the default treatment. Morphological pattern of in-stent restenosis according to the modified Mehran classification adopted for bifurcation lesions was assessed with bifurcation dedicated quantitative coronary angiographic software (CAAS 5.11, Pie Medical Imaging BV, the Netherlands). Results. In total, 445 patients (222 patients in BiOSS group and 223 patients in DES group) were included into the analysis. In BiOSS group 24 cases of angiographic restenosis (10.8%) were recorded, and in DES group—17 cases (7.6%) at 12 months follow-up (angiographic control rate at follow-up—90.3%). In the BiOSS group most frequent medina classification in restenotic cases was 0.0.1 (25%), whereas in DES—0.0.1 and 0.1.1 (23.5% each). In multivariate regression analysis proximal optimization technique was associated with the lowest chance for restenosis (OR 0.15, 95% CI 0.06–0.33), whereas diabetes on insulin was associated with the highest risk of restenosis (OR 4.21, 95% CI 1.48–11.44). Conclusions. The angiographic restenosis pattern and rate was similar between BiOSS stents and DES in coronary bifurcation lesions.

Immunosuppressive Therapy for Restenosis Prevention after Coronary Bare-Metal Stent Implantation -A Meta-Analysis

Background: Previous studies revealed controversial results regarding the prevention of in-stent restenosis after coronary bare-metal stents (BMS) placement with systemic administration of immunosuppressive drugs. We therefore conducted a meta-analysis to investigate the role played by immunosuppressive therapy (IST) in reducing both in-stent restenosis and adverse clinical events after BMS implantation. Methods: We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases for randomized, controlled studies that investigated the therapeutic effects of IST after BMS insertions. Endpoints assessed were: (1) angiographic restenosis by the end of at least 6 months of follow-up; (2) target vessel revascularization (TVR); and (3) risk of major adverse cardiovascular events (MACE). MACE was defined as death, myocardial infarction and TVR. Results: Nine randomized, controlled trials including 1576 patients (mean age 62 years; follow-up of 6-12 months) were included in this analysis. Meta-analysis showed periprocedural IST + BMS significantly reduced in-stent restenosis as compared to BMS alone (RR: 0.59 [0.39-0.90], P = 0.01). In particular, IST reduced restenosis in high-risk patients (defined as patients with mean reference diameter < 3.0 mm or high periprocedural C-reactive protein level) (RR: 0.34 [0.15,0.74], P = 0.006) rather than in low-risk patients ( P for interaction = 0.06). Similarly, IST also reduced the risk of MACE (RR: 0.63 [0.50-0.80], P < 0.01) and TVR (RR: 0.57 [0.33-0.97], P = 0.04). Conclusions: Periprocedural IST reduces the risk of angiographic restenosis, TVR and MACE in patients with BMS implantation. The advantage of IST is driven mainly by a lower risk of in-stent restenosis in high-risk patients. Key words: immunosuppressive therapy, restenosis, bare-metal stents , meta-analysis

Treatment of In-Stent Restenosis by Excimer Laser Coronary Atherectomy and Drug-Coated Balloon: Serial Assessment with Optical Coherence Tomography

Objectives. We aimed to compare the results of neointimal modification before drug-coated balloon (DCB) treatment with excimer laser coronary atherectomy (ELCA) plus scoring balloon predilation versus scoring balloon alone in patients presenting with in-stent restenosis (ISR).Background. Treatment of ISR with ELCA typically results in superior acute gain by neointima debulking. However, the efficacy of combination therapy of ELCA and DCB remains unknown.Methods. A total of 42 patients (44 ISR lesions) undergoing DCB treatment with ELCA plus scoring balloon (ELCA group, n = 18) or scoring balloon alone (non-ELCA group, n = 24) were evaluated via serial assessment by optical coherence tomography (OCT) performed before, after intervention, and at 6 months.Results. Although there was significantly greater frequency of diffuse restenosis and percent diameter stenosis (%DS) after intervention in the ELCA group, comparable result was shown in %DS, late lumen loss, and binary angiographic restenosis at follow-up. On OCT analysis, a decreased tendency in the minimum lumen area and a significant decrease in the minimum stent area were observed in the ELCA group between 6-month follow-up and after intervention (-0.89 ± 1.36 mm2vs. -0.09 ± 1.25 mm2, p = 0.05, -0.49 ± 1.48 mm2vs. 0.28 ± 0.78 mm2, p = 0.03, respectively). The changes in the neointimal area were similar between the groups, and target lesion revascularization showed comparable rates at 1 year (11.1% vs. 11.4%, p = 0.85).Conclusions. Despite greater %DS after intervention, ELCA before DCB had possible benefit for late angiographic and clinical outcome.

Macrophage-derived MMP-8 determines smooth muscle cell differentiation from adventitia stem/progenitor cells and promotes neointima hyperplasia

Aims Emerging evidence has suggested that adventitia stem/progenitor cells (AdSPCs) migrate into the intima of arteries in response to injury, where they differentiate towards smooth muscle cells (SMCs) and participate in neointimal hyperplasia. We have previously identified matrix metalloproteinase-8 (MMP8) as a key player in atherogenesis. In this study, we aimed to investigate the functional roles of macrophage-derived MMP8 in AdSPC differentiation and injury-induced arterial remodelling. Methods and results We first observed an important role for MMP8 in SMC differentiation from embryonic stem cells, but this effect was not seen in AdSPCs. Instead, through macrophages/AdSPCs co-culture and macrophage conditional culture medium studies, we have demonstrated that the MMP8 protein secreted from macrophages promotes SMC differentiation from AdSPCs. Mechanistically, we showed that macrophage-derived MMP8 promotes SMC differentiation from AdSPCs through modulating transforming growth factor-β activity and a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10)/Notch1 signalling. We further demonstrated that the binding site for CBF1, Suppressor of Hairless, and Lag-1 (CSL) within SMC gene promoters is responsible for Notch1 mediated SMC differentiation. Finally, we demonstrated that macrophage-derived MMP8 increased injury-induced neointimal SMC hyperplasia by activating ADAM10/Notch1 signalling. Conclusions We have identified macrophage-derived MMP8 as a regulator in SMC differentiation from AdSPCs and neointimal SMC hyperplasia in response to injury. Our data provide new insights into the roles of MMP8 in AdSPC differentiation and the pathogenesis of neointima formation in the context of angiographic restenosis, and therefore may aid in the development of novel therapeutic agents for the prevention of this disease.

Long-term outcome of stenting for atherosclerotic renal artery stenosis and the effect of angiographic restenosis

Background Symptomatic renal artery stenosis (RAS) is mainly treated with pharmacological blood pressure control, sometimes with percutaneous transluminal renal angioplasty (PTRA). It is unclear if PTRA benefits these patients over time. Purpose To determine long-term renal function, morbidity, and mortality in patients with symptomatic RAS treated with PTRA, and whether long-term outcomes are associated with angiographic restenosis. Material and Methods Retrospective single-center, long-term follow-up of 57 patients with atherosclerotic RAS treated with PTRA with stent during 1995–2004 and investigated for restenosis with angiography after one year. Outcomes were retrieved from medical records and from mandatory healthcare registries. Mortality rates were related to expected survival in an age- and gender-matched population, using a life-table database. Surviving patients were assessed with blood pressures, laboratory tests, duplex ultrasonography, and radioisotope renography. Results Median follow-up was 11 years 7 months. Major indications for PTRA were therapy-resistant hypertension and declining renal function. Angiographic restenosis at one year was found in 21 of 57 patients (37%). Thirty-six patients (60%) died during follow-up. Main cause of death was cardiovascular events (54%). Mortality was significantly increased, and morbidity and healthcare utilization were high. Hypertension control during follow-up was stable with persistent need for anti-hypertensive medication, and renal function remained moderately reduced with no long-term difference between patients with vs. without restenosis. Conclusion Long-term prognosis after PTRA for atherosclerotic RAS is dismal, with high mortality and morbidity and reduced renal function, despite maintained hypertension control. Restenosis does not appear to affect late outcome.