Comparison of 1-Month and 12-Month Vessel Responses Between the Polymer-Free Biolimus A9-Coated Stent and the Durable Polymer Everolimus-Eluting Stent.

BACKGROUND: A polymer-free biolimus A9-coated stent (PF-BCS) may achieve better arterial healing than a durable polymer drug-eluting stent owing to its polymer-free feature.Methods and Results: This multicenter, prospective, observational study enrolled 105 patients (132 lesions) who underwent PF-BCS (51 patients, 71 lesions) or durable polymer everolimus-eluting stent (DP-EES, 54 patients, 61 lesions) implantation. Serial coronary angioscopy (CAS) and optical coherence tomography (OCT) examinations were performed at 1 and 12 months, and the serial vessel responses were compared between PF-BCS and DP-EES. The primary outcome measure was the incidence of subclinical intrastent thrombus on CAS. The secondary outcome measures were: adequate strut coverage (≥40 µm) on OCT and maximum yellow color grade on CAS. The incidence of thrombus was high at 1 month (100% vs. 93%, P=0.091), but decreased at 12 months (18% vs. 25%, P=0.56), without a significant difference between PF-BCS and DP-EES. The adequate strut coverage rate was significantly higher (84±14% vs. 69±22%, P<0.001) and yellow color was significantly less intense (P=0.012) at 12 months in PF-BCS than in DP-EES; however, they were not significantly different at 1 month (adequate strut coverage: 47±21% vs. 50±17%, P=0.40; yellow color: P=0.99). CONCLUSIONS: Although the thrombogenicity of PF-BCS was similar to that of DP-EES, the adequate coverage and plaque stabilization rates of PF-BCS were superior to those of DP-EES at 12 months.

Real-world analysis of a Biolimus A9 polymer-free drug-coated stent with very short dual antiplatelet therapy in patients at high bleeding risk.

BACKGROUND: Patients at high risk of bleeding requiring percutaneous coronary intervention (PCI) need careful evaluation of both their thrombotic and their bleeding risks. In these patients, a polymer-free metallic stent coated with biolimus-A9 (BA9-DCS) followed by 1­month dual antiplatelet therapy (DAPT) could be a safe option; however, real-world data are still lacking. We analyzed the performance of the device in a real-world scenario. METHODS: Patients assessed as being at high risk of bleeding with an indication for PCI were treated with BA9-DCS and DAPT consisting of aspirin (100 mg/day) and clopidogrel (75 mg/day) for at least 1 month, followed by either oral anticoagulation or single antiplatelet therapy. No exclusion criteria were used. The primary endpoint was the occurrence of an adverse event after PCI, i.e. severe bleeding requiring hospitalization, ischemic or hemorrhagic stroke, clinically driven stent thrombosis, myocardial infarction or cardiac death. RESULTS: Overall, 89 patients were enrolled in this study [median age 75 (66-81) years; 27 females (30%)] and 171 interventions were performed. During a median follow-up of 203 (145-273) days the primary endpoint occurred in 20 patients (23%): 12 (13%) had clinically significant bleeding, four (5%) ischemic stroke and four (5%) died from cardiac causes related neither to stent thrombosis nor to acute myocardial infarction. Female gender emerged as the only statistically significant predictor of an adverse event (adjusted hazard ratio (HR) 3.3; 95% confidence interval (CI): 1.2-8.7, p = 0.017). CONCLUSION: In real-world patients at high risk of bleeding, implantation of the polymer-free metallic stent coated with Biolimus-A9 (Biofreedom®; Biosensors Europe, Morges, Switzerland) followed by 1 -month DAPT showed encouraging results without any stent thrombosis.

Randomized comparison between 2-link cell design biolimus A9-eluting stent and 3-link cell design everolimus-eluting stent in patients with de novo true coronary bifurcation lesions: the BEGIN trial.

The appropriate stent platform for treating coronary bifurcation lesions (CBLs) remains controversial. Previous bench tests have demonstrated the superiority of a 2-link cell design to 3-link cell design for creating inter-strut dilation at the side branch ostium. This randomized multicenter prospective BEGIN trial compared the biodegradable polymer-based biolimus A9-eluting stent (2-link BES) with the durable polymer-based cobalt chromium everolimus-eluting stent (3-link EES) in 226 patients with de novo CBLs. Patients with true bifurcations, defined as > 50% stenosis in the main vessel and side branch (SB) and an SB diameter > 2.25 mm, were enrolled. Guide wire re-crossing to the distal cell (near the carina) in the jailed SB and final kissing inflation were recommended. The SB angiographic endpoint was < 50% stenosis diameter. Left-main CBLs (13.5% vs. 13.0%) and 2-stent technique (30.6% vs. 22.6%) rates were similar. The primary endpoints (minimum lumen diameter at the SB ostium measured at an independent core laboratory at the 8-month follow-up) were comparable (1.64 ± 0.50 mm vs. 1.63 ± 0.51 mm, p = 0.976). There was no significant difference in composite outcomes of cardiac death, myocardial infarction, or target vascular revascularization at 12 months (7.4% vs. 8.0%, p = 0.894). Two-link BES and 3-link EES showed similar 8-month angiographic and 1-year clinical outcomes for true CBLs.

Twelve-month outcomes of patients unsuitable for prolonged DAPT presenting with an acute coronary syndrome and treated with polymer-free biolimus A9 drug-coated stents.

INTRODUCTION: Prolonged dual anti-platelet therapy (DAPT) is undesirable in certain patients. The biolimus-A9 drug-coated stent (BA9-DCS) has a rapid drug-elution profile allowing shortened DAPT. METHODS: The demographics, procedural data, and clinical outcomes for 505 patients presenting with an ACS to three UK centres and treated with a BA9-DCS stent (PCI-DCS) were collected, and compared to a consecutive ACS cohort of unselected patients treated in the same period with drug-eluting stents (PCI-DES). RESULTS: PCI-DCS patients were older, more often female with hypertension, chronic kidney disease, severe LV dysfunction, and peripheral vascular disease more frequent than the PCI-DES cohort. PCI-DCS patients had a much higher Mehran bleed risk score (21.5 ± 7.7 vs. 15.9 ± 7.7, P < 0.0001). Baseline disease burden was greater in the PCI-DCS cohort with more left main and three vessel disease. During PCI, more stents (1.91 ± 1.1 vs. 1.57 ± 0.94, P < 0.0001), total stent length (38.2 ± 20.8 vs. 31.4 ± 20.3, P < 0.0001) and longer stents (38.2 ± 20.8 vs. 31.4 ± 20.3 mm, P < 0.0001) were used in the PCI-DCS cohort with rotational atherectomy also used more frequently. Physician-recommended DAPT duration was 2.9 ± 3.9 months for PCI-DCS patients and 11.3 ± 2.4 months for PCI-DES patients (P < 0.0001). At 12-month follow-up, definite stent thrombosis (0.6% vs. 1.1%) and TLR (3.2% vs. 2.7%) rates were similar between the two groups. After adjustment for baseline differences, there were no statistically significant differences in death and combined MACE rates at 12 months. CONCLUSIONS: The outcomes of patients treated with polymer-free BA9 drug-coated stent who present with an ACS and who were deemed unsuitable for prolonged DAPT are encouraging. Further studies are warranted.

Vascular response to biolimus A-9 eluting stent in patients with shorter and prolonged dual antiplatelet therapy: optical coherence tomography sub-study of the NIPPON trial.

Dual antiplatelet therapy (DAPT) with thienopyridine and aspirin is the standard care for the prevention of stent thrombosis. However, the optimal duration and effect of the duration of DAPT on intra-stent thrombus (IS-Th) formation are unknown. The NIPPON study (Nobori Dual Antiplatelet Therapy as Appropriate Duration) was an open label, randomized multicenter, assessor-blinded, trial designed to demonstrate the non-inferiority of shorter (6-month) DAPT to prolonged (18-month) DAPT, after biolimus A9 eluting stent implantation in 3773 patients at 130 sites in Japan. Among them, 101 patients were randomly allocated for an optical coherence tomography (OCT) sub-study to assess the difference of local IS-Th formation between the two groups. In addition to standard OCT parameters, the number of IS-Th formed was counted in each target stent at 8 months. Baseline patient characteristics were not different between the 6- and 18-month groups. IS-Th was detected in 9.8% of the cases and the presence of IS-Th was not significantly different between the two groups (10.9% in 6-month vs. 9.1% in 12-month, P = 0.76). Furthermore, the number of IS-Th formed was not significantly different between the two groups. This OCT sub-study was in line with the main NIPPON study which demonstrated the non-inferiority of 6-month DAPT to 18-month DAPT. Shorter DAPT duration did not promote progressive IS-Th formation at the mid-term time point.

Developmental and reproduction toxicity studies of Biolimus A9 in SD rats.

Biolimus A9 (BA9) is a novel rapamycin derivative. In this report we evaluated the potential toxicity of BA9 in a developmental and reproduction toxicity study (segment Ⅰ, Ⅱ, Ⅲ). In segment I, body weight gains in F0 rats receiving 0.80 mg/kg/day were decreased. A lower fertility index of males was observed and females failed to become pregnant in the 0.80 mg/kg/day group. The number of live fetuses and implantations were decreased while the number of dead fetuses, resorptions, and implantation losses were increased in the 0.12 mg/kg/day group. In segment Ⅱ, maternal toxicity: body weight gains in F0 females receiving 0.036 and 0.090 mg/kg/day group were decreased. Embryo toxicity: In the 0.090 mg/kg/day group, weights and body lengths of fetuses were decreased, the numbers of viable fetuses was decreased and resorbed fetuses increased. Teratogenic effects: The percent of visceral variations and skeletal variations were both increased in the 0.090 mg/kg/day group. In segment Ⅲ, dosing F0 rats with BA9 at dose levels of 0.12 and 0.80 mg/kg/day resulted in reproductive and maternal toxicity, consisting of prolonged labor, dystocia, increased mortality, along with reductions in lactation food consumption. F1 rats in the 0.12 mg/kg/day group showed reproductive and developmental toxicity consisting of body weight decreases, decreased food consumption after weaning and a reduction in the gestation index of pregnant rats. Based on these findings, the no-observed-adverse-effect-level (NOAEL) of BA9 toxicity in segment Ⅰ and Ⅲ was 0.02 mg/kg/day. The NOAEL in segment Ⅱ was 0.015 mg/kg/day.

Design and rationale of a prospective, randomized, non-inferiority trial to determine the safety and efficacy of the Biolimus A9™ drug coated balloon for the treatment of in-stent restenosis: First-in-man trial (REFORM).

BACKGROUND: Drug-coated balloon (DCB) angioplasty with paclitaxel-eluting devices is an established treatment for coronary in-stent restenosis (ISR). Biolimus A9™ (BA9), a sirolimus analogue with enhanced lipophilicity, may facilitate enhanced local drug delivery into vascular tissue. A novel DCB coated with Biolimus A9™ represents an alternative to traditional paclitaxel- and sirolimus-coated devices. Hence, we sought to investigate the safety and efficacy of this novel DCB in the treatment of coronary ISR. METHODS AND DESIGN: REFORM (NCT04079192) is a prospective, multicenter, single blind, randomized controlled trial comparing the BA9-DCB (Biosensors Europe SA, Morges, Switzerland) to the paclitaxel-coated SeQuent® Please DCB (Braun Melsungen AG, Germany) in the treatment of coronary ISR. A total of 201 patients with coronary artery disease and an indication for interventional treatment of ISR in a bare-metal stent (BMS) or drug-eluting stent (DES) have been randomized 2:1 to receive treatment with the BA9- or the paclitaxel-DCB comparator. Patients were enrolled across 24 investigational centers in Europe and Asia. The primary endpoint is percent diameter stenosis (%DS) of the target segment as assessed by quantitative coronary angiography (QCA) at 6 months. Key secondary endpoints are in-stent late lumen loss, binary restenosis, target lesion failure, target vessel failure, myocardial infarction and death at 6 months. Subjects will be followed for 24 months from enrolment. IMPLICATIONS: The REFORM trial will seek to prove that the BA9-DCB is non-inferior to the standard paclitaxel-DCB comparator in the treatment of coronary ISR with respect to %DS at 6 months and has similar safety characteristics.

Observation of early strut coverage after polymer-free biolimus-A9 coated stent by optical frequency domain imaging.

An 80-year-old male patient with an acute myocardial infarction in the mid left anterior descending artery was treated with a BioFreedom stent (2.5 × 24 mm) (Biosensors Inc., Newport Beach, CA, USA). Thirty days post procedure, the patient was re-admitted with chest pain. A significant coronary artery stenosis in the mid left anterior descending artery more progressive than the previous one (not involving proximal stent-edge) was treated with percutaneous coronary intervention. Following this, optical frequency domain imaging of the BioFreedom stent revealed a fully expanded stent with complete stent apposition in its entire length and strut coverage with neointimal hyperplasia. .

Efficacy of biolimus A9-eluting stent for treatment of right coronary ostial lesion with intravascular ultrasound guidance: a multi-center registry.

The aim of this study was to assess the efficacy of a biolimus A9-eluting stent in patients with a right coronary artery (RCA) ostial lesion. Ostial lesions of the RCA have been a limitation of percutaneous coronary intervention even in the drug-eluting stent (DES) era. However, clinical outcomes after the deployment of a second generation DES to an RCA ostial lesion with intravascular ultrasound (IVUS) guidance have not been fully elucidated. From September 2011 to March 2013, 74 patients were enrolled in 17 centers from Japan. RCA ostial lesion was defined as de novo significant stenotic lesion located within 15 mm from ostium. IVUS was used for all cases to confirm the location of ostium and evaluate stent coverage of ostium. Patients with hemodialysis were excluded. The primary endpoint is a major adverse cardiac event (MACE) at 1 year. Forty two percent of patients had multi-vessel disease. Angiographically severe calcification was observed in 26% of the lesions. The mean stent diameter was 3.3 ± 0.3 mm (3.5 mm, 72%, 3.0 mm, 25%, and 2.75 and 2.5 mm, 3%), stent length was 17.5 ± 5.8 mm, and dilatation pressure of stenting was 15.6 ± 4.1 atm. RCA ostium was covered by stent in all lesions in IVUS findings. Post dilatation was performed for 64% of lesions (balloon size 3.7 ± 0.6 mm). MACE rate at 1 year was 5.4% (target lesion revascularization 5.4%, myocardial infarction 1.2%, and no cardiac death). The biolimus A9-eluting stent for RCA ostial lesions with IVUS guidance showed favorable results at 1-year follow-up.

Intravascular imaging comparison of two metallic limus-eluting stents abluminally coated with biodegradable polymers: IVUS and OCT results of the DESTINY trial.

We sought to compare, by means of IVUS and OCT imaging, the performance of a novel sirolimus-eluting drug-eluting stent (DES) with biodegradable polymer (Inspiron™) to the Biomatrix™ DES. From the DESTINY trial, a total of 70 randomized patients (2:1) were enrolled in the IVUS substudy (Inspiron™, n = 46; Biomatrix™: n = 20) while 25 patients were evaluated with OCT (Inspiron™, n = 19; Biomatrix™: n = 06) at 9-month follow-up. The main endpoints were % of neointimal tissue obstruction (IVUS) and neointimal stut coverage (OCT) at 9 months. Patients treated with both DES had very little NIH formation at 9 months either by IVUS (% of NIH obstruction of 4.9 ± 4.1 % with Inspiron™ vs. 2.7 ± 2.9 % with Biomatrix™, p = 0.03) or by OCT (neointimal thickness of 144.2 ± 72.5 µm Inspiron™ vs. 115.0 ± 53.9 µm with Biomatrix™, p = 0.45). Regarding OCT strut-level assessment, again both devices showed excellent 9-month performance, with high rates of strut coverage (99.49 ± 1.01 % with Inspiron™ vs. 97.62 ± 2.21 % with Biomatrix™, p < 0.001) and very rare malapposition (0.29 ± 1.06 % with Inspiron™ vs. 0.53 ± 0.82 % with Biomatrix™, p = 0.44). Patients with any uncovered struts were more frequently identified in the Biomatrix™ group (9.78 ± 7.13 vs. 2.29 ± 3.91 %, p < 0.001). In the present study, midterm IVUS and OCT evaluations showed that both new generation DES with biodegradable polymer were effective in terms of suppressing excessive neointimal response, with very high rates of apposed and covered struts, suggesting a consistent and benign healing pattern.

Polymer-free Biolimus A9-coated stents in the treatment of de novo coronary lesions with short DAPT: 9-month angiographic and clinical follow-up of the prospective, multicenter BioFreedom USA clinical trial.

BACKGROUND: BioFreedom is a polymer- and carrier-free drug-coated stent that delivers Biolimus A9 to the vessel wall. Our purpose was to evaluate the efficacy and safety of this DCS in patients with short-duration dual antiplatelet therapy. METHODS: The BioFreedom US IDE feasibility trial was a single-arm, open-label, prospective study of patients requiring stenting of de novo lesions. Patients received 3 months of DAPT, repeat angiography at 9 months, and clinical follow-up at multiple intervals. A subgroup also underwent intravascular ultrasound (IVUS) interrogation. The primary safety end point was major adverse cardiac events, defined as a composite of cardiac death, myocardial infarction, target lesion revascularization, or stent thrombosis. The primary efficacy end point, in-stent late lumen loss at 9 months, was compared with a historical control from a first-generation paclitaxel-eluting stent. RESULTS: A total of 72 patients from 10 sites received BioFreedom DCS implanted in 83 de novo lesions. At 9 months, the incidence of composite MACE was 8.4%, and TLR was 1.5%. Short DAPT was safe without occurrence of stent thrombosis. The primary end point of LLL was 0.32±0.53 mm. Paired IVUS analyses comparing postprocedural with 9-month measurements showed low in-stent neointimal volume obstruction (5.39±5.28%) and low neointimal hyperplasia (7.43±8.04 mm3). CONCLUSIONS: This study's angiography and IVUS assessments demonstrated that the BioFreedom DCS has anti-restenotic efficacy similar to first-generation DES. In the absence of concerning safety signals, this DCS should be considered effective and safe for patients who require a shorter duration of DAPT.

Evaluation and medical therapy for coronary endothelial dysfunction induced by sirolimus-eluting stent in patient with an atherosclerotic lesion of the left main coronary artery: Case report.

Sirolimus-eluting stents (SES), especially those deployed at distal sites, cause more coronary vasospasm and endothelial dysfunction in the chronic phase compared to bare-metal stents (BMS). In comparison, endothelial dysfunction is less frequently induced by the Biolimus-A9 eluting stent (BES). A 75-year-old man with effort-induced angina pectoris previously underwent a total of three SES implantations in the left anterior descending coronary artery (LAD) and right coronary artery (RCA) in 2010 and 2011. He was referred to our hospital for the management of chest discomfort at rest in August 2014. We diagnosed this patient with coronary spastic angina (CSA) and coronary endothelial dysfunction (CED) induced by the SES, together with an atherosclerotic lesion in the left main coronary artery (LMCA). Adequate medication for CSA and CED and intervention for the atherosclerotic lesion contributed to improvement of vascular function and disappearance of his symptoms. .

Nobori-Biolimus-Eluting Stents versus Resolute Zotarolimus-Eluting Stents in Patients Undergoing Coronary Intervention: A Propensity Score Matching.

PURPOSE: To compare the 1-year outcomes of a durable polymer Zotarolimus-eluting stent (ZES) versus a biodegradable polymer Biolimus-eluting stent (BES) in patients undergoing percutaneous coronary intervention. MATERIALS AND METHODS: A total of 2083 patients from 2 different registries, 1125 treated with BES in NOBORI registry and 858 received ZES in CONSTANT registry were included in this study. Clinical outcomes were compared with the use of propensity score matching (PSM). The primary endpoint was a composite of major adverse cardiovascular and cerebrovascular events (MACCEs) including cardiac death, myocardial infarction, clinically driven target lesion revascularization and stroke. Secondary end points were individual components of MACCEs as well as the incidence of stent thrombosis at 1-year follow-up. RESULTS: After PSM, 699 matched pairs of patients (n=1398) showed no significant difference between BES and ZES in the risk of composite MACCEs at 1 year (2.6% vs. 1.7%; p=0.36). Cardiac death was not statistically different between groups (0.7% vs. 0.4%, p=0.73). Target lesion revascularization rate was also similar between BES and ZES (1.1% vs. 0.7%, p=0.579). Non-Q wave myocardial infarction, as well as target-vessel revascularization rate, was similar between the two groups (0.14% for BES and 0.72% for ZES). Both stent types were excellent with no cases of stent thrombosis and rate of Q wave myocardial infarction reported during the follow-up period. CONCLUSION: In this cohort of patients treated with BES or ZES, the rate of MACCEs at 1 year was low and significantly not different between both groups.

One-Year Outcome of Everolimus-Eluting Stents Versus Biolimus-Eluting Stents in Patients Undergoing Percutaneous Coronary Intervention.

Background: The biolimus-eluting stent (BES), with a biodegradable polymer, has not been previously compared with the everolimus-eluting stent (EES), as a second-generation drug-eluting stent (DES).We sought to compare the 1-year outcome between the PROMUS™ stent (EES type) and the BioMatrix™ stent (BES type). Methods: From March 2008 to September 2011, all patients treated with the PROMUS™ stent or the BioMatrix™ stent for coronary artery stenosis at Tehran Heart Center were enrolled. The primary end points were 1-year adverse events, comprising death, myocardial infarction, target vessel revascularization, and target lesion revascularization. The secondary end point was stent thrombosis. The Cox proportional hazard model was used to assess the adjusted association between the stent type and the follow-up outcome. Results: From 949 patients (66.3% male, mean age =59.48 ± 10.46 y) with 1,018 treated lesions, 591 patients (630 lesions, 65.1% male, mean age = 59.24 ± 10.23 y) received the PROMUS™ stent and 358 patients (388 lesions, 68.2% male, mean age = 59.88 ± 10.83 y) were treated with the BioMatrix™ stent. Before adjustment, the rate of the primary end points was 3.2% and 3.4% in the EES and BES, respectively (p value = 0.925, HR (EES to BES) = 1.035, 95% CI: 0.50 to 2.13). The rate of stent thrombosis was 2% and 1.7% in the EES and BES, respectively (p value = 0.698). After adjustment on confounder variables, there was no statistically significant difference in major adverse cardiac events between the PROMUS™ stent and the BioMatrix™ stent (p value = 0.598, HR (EES to BES) = 0.817, 95% CI: 0.39 to 1.73). Conclusion: At 1 year's follow-up, the BES and EES showed similar safety and efficacy rates in the patients undergoing percutaneous coronary intervention with a relatively low rate of adverse events in the 2 groups.

Favorable outcomes in octogenarians treated with bioresorbable polymer drug-eluting stent.

AIM: As a result of a higher prevalence of comorbidities, elderly adults are often underrepresented in clinical trials, and more often experience complications during percutaneous coronary intervention. Our aim was to evaluate clinical outcomes of patients older than 80 years, compared with their younger counterparts, when bioresorbable polymer biolimus A9 drug-eluting stent is used for their treatment. METHODS: The prospective, observational e-Nobori registry was created to validate the safety and efficacy of bioresorbable polymer drug-eluting stent in unselected patients. The primary end-point of the study was freedom from target lesion failure defined as a composite of cardiac death, target vessel-related myocardial infarction and clinically-driven target lesion revascularization at 1 year. RESULTS: There were 781 (7.8%) octogenarians, they were less frequently male (62% vs 77%; P < 0.0001) and more often presented as acute coronary syndrome (44% vs 39%; P = 0.0182). The index percutaneous coronary intervention success was lower in the elderly patients (98% vs 99%; P = 0.0398). One-year follow up was completed for 97% of the elderly patients and 99% of the younger patients. The difference in target lesion failure (3.33% vs 2.83%; log-rank P = 0.0114) was mainly driven by increased mortality in octogenarians (3.73% vs 1.47%; P < 0.0001). Elderly patients had more bleeding and vascular complications (2.67% vs 1.05%; P = 0.0001). CONCLUSIONS: Despite advanced age, multiple comorbidities and complexity of treated lesions, clinical outcomes are favorable in octogenarians treated by bioresorbable polymer biolimus A9 drug-eluting stent. Geriatr Gerontol Int 2016; 16: 1246-1253.

Organ transplantation and drug eluting stents: Perioperative challenges.

Patients listed for organ transplant frequently have severe coronary artery disease (CAD), which may be treated with drug eluting stents (DES). Everolimus and zotarolimus eluting stents are commonly used. Newer generation biolimus and novolimus eluting biodegradable stents are becoming increasingly popular. Patients undergoing transplant surgery soon after the placement of DES are at increased risk of stent thrombosis (ST) in the perioperative period. Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor such as clopidogrel, prasugrel and ticagrelor is instated post stenting to decrease the incident of ST. Cangrelor has recently been approved by Food and Drug Administration and can be used as a bridging antiplatelet drug. The risk of ischemia vs bleeding must be considered when discontinuing or continuing DAPT for surgery. Though living donor transplant surgery is an elective procedure and can be optimally timed, cadaveric organ availability is unpredictable, therefore, discontinuation of antiplatelet medication cannot be optimally timed. The type of stent and timing of transplant surgery can be of utmost importance. Many platelet function point of care tests such as Light Transmittance Aggregrometry, Thromboelastography Platelet Mapping, VerifyNow, Multiple Electrode Aggregrometry are used to assess bleeding risk and guide perioperative platelet transfusion. Response to allogenic platelet transfusion to control severe intraoperative bleeding may differ with the antiplatelet drug. In stent thrombosis is an emergency where management with either a drug eluting balloon or a DES has shown superior outcomes. Post-transplant complications often involved stenosis of an important vessel that may need revascularization. DES are now used for endovascular interventions for transplant orthotropic heart CAD, hepatic artery stenosis post liver transplantation, transplant renal artery stenosis following kidney transplantation, etc. Several antiproliferative drugs used in the DES are inhibitors of mammalian target of rapamycin. Thus they are used for post-transplant immunosuppression to prevent acute rejection in recipients with heart, liver, lung and kidney transplantation. This article describes in detail the various perioperative challenges encountered in organ transplantation surgery and patients with drug eluting stents.

One-year outcome of biolimus eluting stent with biodegradable polymer in all comers: the Italian Nobori Stent Prospective Registry.

OBJECTIVES: INSPIRE-1 (Italian Nobori Stent ProspectIve REgistry-1) was designed and conducted to assess clinical performance of Nobori biolimus A9-eluting stent (BES) implantation in an unrestricted "real-world" cohort of patients. METHODS: Unrestricted consecutive high-risk patients treated with BES with biodegradable polymer (Nobori, Terumo, Tokyo, Japan) between February 2008 and July 2012 were prospectively enrolled in an independent multicenter registry and divided in two groups: complex and non complex lesions. RESULTS: 1066 patients (1589 lesions) treated with Nobori BES were analyzed. The majority of patients (57%) were treated for at least one complex lesion and presented a high-risk clinical profile (previous CABG 17.6%, diabetes mellitus 33.1%, chronic kidney disease 14.3%). Angiographic success rate was achieved in 96.2% cases. At 1 year, the primary endpoint, (composite of cardiac death, myocardial infarction, and clinically driven target vessel revascularization), occurred in 39 (4.0%) patients, and was higher in the complex lesions (5.2% vs. 2.5%, P = 0.032). Target lesion failure (TLF, secondary endpoint) occurred in 45 (4.6%) patients, and was more frequent in the complex lesions group (6.2% vs. 2.7%, P = 0.011), mainly due to a higher incidence of any target lesion revascularization (4.8% vs. 2.7%; P = 0.095). Definite and probable stent thrombosis (ST) rate was 0.6% and 0.5% respectively, with no difference between groups. CONCLUSIONS: In unrestricted daily practice, BESs were implanted predominantly in high risk patients with complex lesions. Despite this, the Nobori BES was associated with a relatively low rate of primary endpoint and TLF, with a higher risk in patients with complex lesions.

Comparison of newer-generation drug-eluting with bare-metal stents in patients with acute ST-segment elevation myocardial infarction: a pooled analysis of the EXAMINATION (clinical Evaluation of the Xience-V stent in Acute Myocardial INfArcTION) and COMFORTABLE-AMI (Comparison of Biolimus Eluted From an Erodible Stent Coating With Bare Metal Stents in Acute ST-Elevation Myocardial Infarction) trials.

OBJECTIVES: This study sought to study the efficacy and safety of newer-generation drug-eluting stents (DES) compared with bare-metal stents (BMS) in an appropriately powered population of patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Among patients with STEMI, early generation DES improved efficacy but not safety compared with BMS. Newer-generation DES, everolimus-eluting stents, and biolimus A9-eluting stents, have been shown to improve clinical outcomes compared with early generation DES. METHODS: Individual patient data for 2,665 STEMI patients enrolled in 2 large-scale randomized clinical trials comparing newer-generation DES with BMS were pooled: 1,326 patients received a newer-generation DES (everolimus-eluting stent or biolimus A9-eluting stent), whereas the remaining 1,329 patients received a BMS. Random-effects models were used to assess differences between the 2 groups for the device-oriented composite endpoint of cardiac death, target-vessel reinfarction, and target-lesion revascularization and the patient-oriented composite endpoint of all-cause death, any infarction, and any revascularization at 1 year. RESULTS: Newer-generation DES substantially reduce the risk of the device-oriented composite endpoint compared with BMS at 1 year (relative risk [RR]: 0.58; 95% confidence interval [CI]: 0.43 to 0.79; p = 0.0004). Similarly, the risk of the patient-oriented composite endpoint was lower with newer-generation DES than BMS (RR: 0.78; 95% CI: 0.63 to 0.96; p = 0.02). Differences in favor of newer-generation DES were driven by both a lower risk of repeat revascularization of the target lesion (RR: 0.33; 95% CI: 0.20 to 0.52; p < 0.0001) and a lower risk of target-vessel infarction (RR: 0.36; 95% CI: 0.14 to 0.92; p = 0.03). Newer-generation DES also reduced the risk of definite stent thrombosis (RR: 0.35; 95% CI: 0.16 to 0.75; p = 0.006) compared with BMS. CONCLUSIONS: Among patients with STEMI, newer-generation DES improve safety and efficacy compared with BMS throughout 1 year. It remains to be determined whether the differences in favor of newer-generation DES are sustained during long-term follow-up.

Long-term outcomes of biodegradable polymer versus durable polymer drug-eluting stents in patients with diabetes a pooled analysis of individual patient data from 3 randomized trials.

BACKGROUND: There is ongoing debate on the optimal drug-eluting stent (DES) in diabetic patients with coronary artery disease. Biodegradable polymer drug-eluting stents (BP-DES) may potentially improve clinical outcomes in these high-risk patients. We sought to compare long-term outcomes in patients with diabetes treated with biodegradable polymer DES vs. durable polymer sirolimus-eluting stents (SES). METHODS: We pooled individual patient-level data from 3 randomized clinical trials (ISAR-TEST 3, ISAR-TEST 4 and LEADERS) comparing biodegradable polymer DES with durable polymer SES. Clinical outcomes out to 4 years were assessed. The primary end point was the composite of cardiac death, myocardial infarction and target-lesion revascularization. Secondary end points were target lesion revascularization and definite or probable stent thrombosis. RESULTS: Of 1094 patients with diabetes included in the present analysis, 657 received biodegradable polymer DES and 437 durable polymer SES. At 4 years, the incidence of the primary end point was similar with BP-DES versus SES (hazard ratio = 0.95, 95% CI = 0.74-1.21, P = 0.67). Target lesion revascularization was also comparable between the groups (hazard ratio = 0.89, 95% CI = 0.65-1.22, P = 0.47). Definite or probable stent thrombosis was significantly reduced among patients treated with BP-DES (hazard ratio = 0.52, 95% CI = 0.28-0.96, P = 0.04), a difference driven by significantly lower stent thrombosis rates with BP-DES between 1 and 4 years (hazard ratio = 0.15, 95% CI = 0.03-0.70, P = 0.02). CONCLUSIONS: In patients with diabetes, biodegradable polymer DES, compared to durable polymer SES, were associated with comparable overall clinical outcomes during follow-up to 4 years. Rates of stent thrombosis were significantly lower with BP-DES.

Experience with BioMatrix BES and other DES in all-comers setting: a retrospective overview.

New generation DES are effectively used in all spectrum of coronary artery diseases (CAD) and are replacing earlier DES and BMS. Biolimus A9™-eluting stent is a new generation DES containing the anti-proliferative drug biolimus A9™ incorporating a biodegradable abluminal coating that leaves a polymer-free stent after drug release enhancing strut coverage while preventing neointimal hyperplasia. A retrospective data analysis was done in patients treated with DES, with a major share of Biolimus A9™ (BA9™) drug-eluting stents (DES) at Bombay Hospital, Mumbai. A total of 158 patients with 219 lesions were treated with DES, comprising Biolimus A9-eluting stent and others and the major adverse cardiac events (MACE) rate and stent thrombosis (ST) at 1, 6, 12 months and 24 months were analyzed. Mace rate was 3.16% for average follow-up of 19 months. There were 3 cases of ST (2 of acute and 1 of subacute onset) and one non-cardiac death reported during this time. This retrospective data demonstrates good one- and two-year clinical safety and efficacy of DES, especially of BioMatrix stents in real world setting.