Microcrystalline paclitaxel-coated balloon for revascularization of femoropopliteal artery disease: Three-year outcomes of the randomized BIOPAC trial

The aim of the BIOPAC trial was to determine long-term safety and efficacy of a novel microcrystalline paclitaxel-coated balloon (mcPCB) with a biocompatible polymer as an excipient in the treatment of occlusive femoropopliteal lesions. In this first-in-human prospective controlled randomized trial, 66 patients with femoropopliteal, symptomatic (Rutherford stages 2B to 5) occlusive arterial disease were randomized to either mcPCB (study group) or POBA (plain old balloon angioplasty) (control group) on a 1:1 basis. Late lumen loss (LLL) at 6 months was the primary endpoint of the study and serious adverse events (SAE: death, amputation, repeated revascularization) were considered a composite secondary endpoint. Routine angiography was scheduled for all study subjects at 6-month follow-up; outpatient appointments were scheduled at 12 and 36 months after intervention. At 6 months, the LLL was 63% lower in the mcPCB group compared to the POBA group (0.52 ± 1.2 vs 1.39 ± 1.1 mm; psup < 0.01). Binary restenosis occurred in 23% vs 52% of patients ( p = 0.02). At 3 years, the prevalence of SAE was significantly lower in the mcPCB group (33.3 vs 63.3%; p = 0.02), which mainly resulted from a twofold reduction in target vessel revascularization rate (28.6 vs 59.3%; p = 0.02). The difference in mortality was nonsignificant (7.4 vs 14.3%; p = 0.42). Patients with mcPCB were less symptomatic and less likely to adhere to secondary prevention measures. In this pivotal trial, a novel mcPCB proved superior to POBA concerning LLL at 6-month follow-up, and SAE at 12 months. This result was sustained up to 3 years. There was no difference between groups regarding mortality. ClinicalTrials.gov Identifier: NCT02145065

Paclitaxel Coated Balloon vs. Bare Metal Stent for Endovascular Treatment of Symptomatic Vertebral Artery Origin Stenosis Patients: Protocol for a Randomized Controlled Trial

Background: Stenting treatment for refractory symptomatic patients with vertebral artery origin stenosis (VAOS) is safe; however, there is a high rate of in-stent restenosis. Although drug-eluting stents can reduce the incidence of restenosis to some extent, there is still a risk caused by stent fracture. Drug-coated balloon (DCB) has been proven to reduce the rate of restenosis in peripheral and coronary artery disease. DCB can prevent inflammation caused by extraneous material stimulation and allow the subsequent treatment that is characteristic of “leave nothing behind.” The purpose of this trial is to compare the efficacy and safety of DCB and bare metal stent (BMS) in the treatment of VAOS.Method/Design: This trial is a 1:1 randomized, controlled, multicenter, non-inferiority trial that compares the DCB to BMS in terms of angiographically assessed target lesion binary restenosis (≥50%) at 12 months in endovascular treatment of symptomatic patients with VAOS.Discussion: A total of 180 patients with symptomatic VAOS who match the trial eligibility criteria will be randomized 1:1 to treatment with DCB (n = 90) or BMS (n = 90). An angiographic core laboratory-adjudicated target lesion binary restenosis (≥50%) at 12 months of follow-up was selected as primary efficacy endpoint to assess the DCB treatment effect. A clinical events committee will assess the safety endpoints of all-cause death, target vessel related transient ischemic attack and ischemic or hemorrhagic stroke events. A data safety monitoring board will periodically review safety data for subject safety, the study conduct, and progress. In this trial, randomization is only allowed after successful pre-dilatation. We anticipate that this trial will provide rigorous data to clarify whether DCBs are beneficial in patients with symptomatic VAOS.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03910166.

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

Impact of hinge motion on stent edge restenosis after new generation drug-eluting-stent implantation in RCA

Background Edge restenosis still occurs after stent implantation, even by using new generation drug-eluting stents (DES) considered to have favorable biomechanical properties. Mechanical stress imposed on the stent edge are thought to be aggravated by hinge motion at a point between the stented and unstented segments, inducing chronic local inflammation and neointimal overgrowth. Purpose The aim of this study was to investigate the association between the development of edge restenosis and hinge motion in right coronary artery (RCA) where the excessive vessel movement is commonly observed. Methods Among consecutive 650 lesions in RCA where new generation DESs were implanted between 2009 and 2019, 427 serial lesions with sets of angiographies at baseline and follow-up (6–18 month) were included. In addition to conventional quantitative angiography analysis, hinge angle at stent edges was measured (Fig. 1). All the appropriate data for intravascular imaging were analyzed for both stent edges and reference segments. Results Binary restenosis occurred in 43 lesions, and 39 of them were referred to re-intervention. Fifty five percent of them were related to stent edges (15 at proximal and 9 at distal edges). Classical risk factors including diabetes and hemodialysis were more prevalent in the restenosis group (p&lt;0.05). Hinge angle was statistically larger in edge restenosis group than body restenosis or no restenosis group (17.3° vs 11.6° vs 10.6°, p&lt;0.001, Fig. 2). In per-edge analysis, hinge angle, dissection and residual plaque ratio were the independent predictors for binary restenosis (Table 1) with the optimal cut-off value of hinge angle 11.5°. The coexistence of excessive hinge angle and residual plaque burden had an amplified effect on the angiographic stenotic progression at stent edge (p for interaction &lt;0.001) and the incidents of binary restenosis (16.7% vs 1.7% p&lt;0.01, Figs. 3,4). Conclusion Substantial stress determined by angulation at the stent edge and its interaction with residual plaque can be considered as one of the plausible mechanisms for edge restenosis. For tortuous RCA lesions, it would be important to decide the stent-landing zone for minimizing hinge motion and optimize the future stent design. Funding Acknowledgement Type of funding source: None

Comparative Effectiveness of Endovascular Treatment Modalities for De Novo Femoropopliteal Lesions: A Network Meta-analysis of Randomized Controlled Trials

Purpose: To report the results of a network meta-analysis of randomized controlled trials (RCTs) comparing multiple endovascular treatments for de novo femoropopliteal lesions. Materials and Methods: The MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases were systematically searched on June 1, 2019, for prospective RCTs comparing 14 treatments [ie, atherectomy, brachytherapy, cryoplasty, cutting balloons, drug-coated balloons, bare nitinol stents, drug-eluting stents (DES), covered stents (CS), and combinations] in the treatment of de novo femoropopliteal lesions. Outcomes were technical success; binary restenosis and target lesion revascularization (TLR) at 6, 12, and/or 24 months; and all-cause mortality at 12 months. Ultimately, 53 articles reporting on 45 studies (91 study arms; 5565 patients) were selected. For the technical success outcome, all types of stents, all balloons, and all atherectomy devices were aggregated in stent, balloon, and atherectomy technology groups, respectively. Results: In terms of technical success for aggregated treatment types, stent technology was the most effective treatment and was better than balloon and atherectomy technologies. In terms of binary restenosis, DES was the most effective single treatment at the 6- and 12-month follow-up and CS at the 24-month follow-up. Both DES and CS were better than the majority of other single treatments, including balloon angioplasty, cutting balloon, cryoplasty, directional atherectomy, and bare nitinol stent during all follow-up periods. In terms of TLR, DES was the second most effective single treatment and the most effective single treatment at the 6- and 12-month follow-up intervals; CS was the most effective single treatment at the 24-month follow-up. Both DES and CS were better than the majority of other single treatments. The 12-month all-cause mortality of both DES and CS were similar to other treatments, whereas cryoplasty seemed to be the least effective treatment with regard to binary restenosis and TLR. Conclusion: Both DES and CS had substantial advantages in terms of restenosis and TLR in femoropopliteal lesions and were similar to aggregate stent technology in terms of technical success. DES performed better within 12 months after operation and CS at ~24 months, but neither had much advantage in terms of mortality. In contrast, cryoplasty seemed to be a less effective treatment.

P2691Excimer laser coronary angioplasty can achieve favorable clinical outocomes for in-stent restenosis lesion with neoatherosclerosis

Background Recent reports revealed that residual area stenosis (% AS) ≤30% after lesion preparation is a suitable predictor for target lesion revascularization (TLR) after drug-coated balloon (DCB) treatment for in-stent restenosis (ISR). Excimer laser coronary angioplasty (ELCA) can obtain larger lumen area and may be more useful for lesion preparation than plain old ballooning (POBA). On the other hands, it has been reported that in-stent neoatherosclerosis (NA) is major cause of restenosis. It is unclear the correlation between NA of ISR and the effect of ELCA. Thus, we compared the influence of NA which was evaluated by optical coherence tomography (OCT) on % AS for ISR treatment between ELCA and DCB (ELCA) group and POBA and DCB (non-ELCA) group and their clinical outcome. Methods We enrolled 58 consecutive ISR lesions which were treated by OCT guidance between July 2014 and July 2018 in our hospital. The lesions were divided into NA and non-NA lesions according to OCT findings. In each lesion, we compared post procedural % AS and % AS change which was calculated by the difference between pre and post procedural % AS between ELCA and non-ELCA groups. In addition, we compared 8-month major advance cardiac events (MACE) defined by composite of binary restenosis and target lesion revascularization (TLR) between ELCA and non-ELCA group in NA lesions. Results There were 19 NA (33.3%) and 39 non-NA lesions. In NA lesions, ELCA group can obtain significantly lower % AS (p=0.02) and significantly larger % AS change (p<0.01) than non-ELCA group, but in non-NA lesions, % AS and %AS change were similar between ELCA and non-ELCA groups (table). In 8-month clinical outcome, non-ELCA group experienced MACE twice as much as ELCA group did. (31% vs 17%) Results of %AS NA lesions (n=19) P value non-NA lesions (n=39) P value ELCA group (n=6) non-ELCA group (n=13) ELCA group (n=17) non-ELCA group (n=22) Post %AS (%) 2±21 26±25 0.02 7±29 23±19 0.07 %AS change (%) 71±15 38±19 <0.01 56±29 44±17 0.11 Conclusion Although neoatherosclerosis is correlated with refractory restenosis, ELCA can improve residual area stenosis in neoatherosclerosis lesions and can achieve better clinical outcomes for in-stent neoatherosclerosis.

Three-Year Results of the Absorb Everolimus-Eluting Bioresorbable Vascular Scaffold in Infrapopliteal Arteries

Purpose: To investigate the midterm performance of the everolimus-eluting Absorb bioresorbable vascular scaffold (BVS) for the treatment of symptomatic infrapopliteal atherosclerotic disease. Methods: A single-center study prospectively enrolled 48 symptomatic patients (mean age 82.1±8.0 years; 27 men) between September 2013 and February 2018 to evaluate the Absorb everolimus-eluting BVS system in distal popliteal and tibial lesions. Mean lesion length was 20.1±10.8 mm. Following predilation, up to 2 BVS were implanted in target lesions in 55 limbs. Clinical and duplex ultrasound follow-up was performed at 1, 3, 6, 12, 24, 36, and 48 months to determine 30-day morbidity and midterm Kaplan-Meier estimates of binary restenosis, clinically-driven target lesion revascularization (CD-TLR), amputation, and mortality. Results: Seventy-one scaffolds were implanted to treat 61 lesions. Technical success was achieved in all patients, with no amputation, death, or target limb bypass surgery within 30 days of the index procedure. There was 1 early thrombotic occlusion of 2 BVS in a previously anticoagulated patient not given antiplatelet medication after the procedure. During a mean follow-up of 24.0±15.3 months, 11 (23%) patients died; the remaining 37 were available for follow-up. Binary restenosis (50%–75%) was detected in 6 (8%) scaffolds. Primary patency estimates at 12, 24, and 36 months were 92.2%, 90.3%, and 81.1%; freedom from CD-TLR estimates were 97.2%, 97.2%, and 87.3% at the same time points. No late scaffold thrombosis has been observed. The majority of the 55 limbs (51, 93%) were clinically improved; 4 (7%) were unchanged. Thirty-six (92%) of 39 limbs treated for tissue loss achieved complete wound healing, with no major amputation (limb salvage 100%). Conclusion: Midterm follow-up demonstrates excellent safety, patency, and freedom from CD-TLR rates using the Absorb bioresorbable vascular scaffold below the knee.

Biomechanics and clinical experience of a 3D biomimicking vascular stent

The presented investigation was designed to assess the biomechanical behavior of a 3D biomimicking self-expanding stent with respect to general technical parameters added by first clinical tests. The test sample was a Veryan Medical Biomimics 3D with 6.0 mm expanded diameter and 80 mm length. The profile of the delivery catheter with mounted stent, the strut thickness, the bending stiffness, the axial stiffness for tension and compression and the length change during expansion were measured. The bending stiffness was 2.73 Nmm², axial stiffness at tension 7.77 N/mm and at compression 97.61 N/mm. The stent shortened during expansion by 11.54 %. Radial force at 5 mm diameter was 2.54 N. Clinical experience provided no stent fractures after 24 months. Duplexsonography showed stent patency without any binary restenosis or intimal hyperplasia.

Abstract 340: Drug-Eluting Balloon Versus Everolimus-Eluting Stent for Restenosis in a Bare-Metal Stent: A Meta-Analysis of Randomized Trials

Background: In-stent restenosis accounts for major morbidity and mortality among patients treated with Bare-Metal Stents (BMS). Early efforts to treat BMS in-stent restenosis with plain balloon angioplasty and first generation drug eluting stents (DES) have been ineffective, leaving drug-eluting balloon (DEB) and second generation DES, such as everolimus eluting stents (EES), as the only remaining options. For BMS in-stent restenosis, studies performed so far have yielded conflicting results, while prior meta-analyses have been influenced by inclusion of observational studies. This is the first meta-analysis to compare EES versus DEB using results from only randomized controlled trials (RCTs). Methods: A systematic search of PUBMED and EMBASE databases was conducted from first available date to August, 2016 for RCTs comparing DEB with EES. Two reviewers evaluated studies for eligibility and extracted data with binary restenosis rate as the main endpoint. We identified 901 unique citations. Odds ratios were pooled using random-effects modeling. Funnel plots were used to assess publication bias. Heterogeneity was assessed using I 2 statistic. All analysis were performed using Review Manager (RevMan) version 5.3 (Cochrane Collaboration, 2014). Results: Three RCTs met study eligibility criteria, with 684 patients and a mean follow-up of 9.5 months. There were 184 and 185 patients in the EES and DEB arms respectively. In pooled analyses, EES was not superior to DEB in binary restenosis rates (pooled odds ratio: 0.76; 95% confidence interval: 0.25-2.32; P=0.14). Heterogeneity was minimal (I 2 = 49%), and the funnel plot did not suggest publication bias. Conclusion: In patients with BMS in-stent restenosis, there were no significant differences in binary restenosis rates between EES and DEB. Our results can enhance physician decision-making regarding choice of revascularization tool in this patient population.