Three-year follow up of biodegradable polymer cobalt-chromium sirolimus-eluting stent (EXCROSSAL) in treating de novo coronary artery disease: Pooled analysis of CREDIT II and CREDIT III trials.

OBJECTIVES: To analyze the 3-year outcomes of the biodegradable polymer cobalt-chromium sirolimus-eluting stent (EXCROSSAL) in CREDIT II AND III TRIALS. BACKGROUND: Though approved by CFDA, the long-term safety and efficacy of EXCROSSAL is still unknown. METHODS: CREDIT II was a randomized trial comparing the EXCROSSAL versus EXCEL stents in patients with up to two de novo coronary lesions, and CREDIT III was a prospective, single-arm study evaluating the efficacy and safety of EXCROSSAL in broad types of de novo coronary artery lesions. We pooled the 3-year follow-up data of the EXCROSSAL arm of the CREDIT II and CREDIT III Trials. The primary outcome was 3-year target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction (TV-MI), and clinically indicated target lesion revascularization (CI-TLR). The patient-oriented composite endpoint (PoCE) (all-cause death, all MI, or any revascularization) and stent thrombosis (ST) were also analyzed. RESULTS: A total of 833 patients were included in this study. The incidence of TLF and PoCE in the 3-year follow-up were 7.6% and 12.5%, respectively. ST occurred in 0.6% of patients. In the subgroup analyses, TLF was significantly higher in small target vessels, multi-lesion PCI, and multi-vessel disease. CONCLUSIONS: The 3-year follow-up analysis confirmed low rates of TLF and ST in EXCROSSAL, which is similar to the most widely used new generation durable polymer drug-eluting stent.

Safety and efficacy of the novel sirolimus-eluting bioresorbable scaffold for the treatment of de novo coronary artery disease: One-year results from a prospective patient-level pooled analysis of NeoVas trials.

OBJECTIVES: This prospective, patient-level analysis assessed the safety and efficacy of NeoVas sirolimus-eluting bioresorbable scaffold (BRS) in patients with coronary lesions. Furthermore, to meet China Food and Drug Administration requirements, we conducted an objective performance criterion study by pooling all patients implanted with the NeoVas BRS in a previous randomized controlled trial (RCT) and registry trial. BACKGROUND: Drug-eluting stent-related permanent vessel caging by metallic struts may lead to several complications associated with percutaneous coronary intervention. BRSs reportedly result in more stent thromboses (ST) in comparison to everolimus-eluting stents. The NeoVas (Lepu Medical, Beijing, China) is a novel sirolimus-eluting poly-l-lactic acid (PLLA)-based BRS whose safety and efficacy remains to be fully elucidated. METHODS: Patient-level data derived from 1,103 patients with de novo native coronary lesions in the NeoVas RCT (n = 278) and NeoVas registry (n = 825) were prospectively collected, pooled, and analyzed. The primary outcome was 12-month target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction, or ischemia-driven-target lesion revascularization. The patient-oriented composite endpoint (PoCE) of all-cause death, all MI, or any revascularization was also analyzed. RESULTS: The 12-month rate of TLF in 1,103 patients (follow-up rate, 99.8%) was 3.0%, significantly lower than the performance goal of 8.5% (P < 0.0001). Furthermore, 50 (5.4%) PoCEs and five definite/probable ST (0.5%) were recorded. CONCLUSIONS: This pooled, patient-level analysis indicates that the NeoVas BRS has promising 1-year efficacy and safety profiles.

Randomized comparison of novel biodegradable polymer and durable polymer-coated cobalt-chromium sirolimus-eluting stents: Three-Year Outcomes of the I-LOVE-IT 2 Trial.

OBJECTIVES: We aimed to compare the long-term outcomes of the novel biodegradable polymer cobalt-chromium sirolimus-eluting stent (BP-SES) versus the durable polymer sirolimus-eluting stent (DP-SES) in the I-LOVE-IT2 trial. BACKGROUNDS: Comparisons of the long-term safety and efficiency of the BP-DES versus the DP-DES are limited. METHODS: A total of 2,737 patients eligible for coronary stenting were randomized to the BP-SES or DP-SES group at a 2:1 ratio. The primary endpoint of target lesion failure (TLF) was defined as a composite of cardiac death, target vessel myocardial infarction (MI), or clinically indicated target lesion revascularization. RESULTS: A three-year clinical follow-up period was available for 2,663 (97.3%) patients. There were no significant differences in TLF (8.9% vs. 8.6%, P = 0.81), patient-oriented composite endpoint (PoCE) (15.2% vs.14.5%, P = 0.63), or individual components between the BP-SES and DP-SES. Definite/probable stent thrombosis (ST) was low and similar at 3 years (0.8% vs. 1.0%, P = 0.64). Landmark analysis of 1-3 years showed that the TLF (2.7% vs. 2.6%, P = 0.81), PoCE (6.2% vs. 5.1%, P = 0.28), and definite/probable ST (0.4% vs. 0.4%, P = 1.00) were comparable between the 2 arms. CONCLUSIONS: In this prospective randomized trial, the BP-SES showed similar clinical results versus the DP-SES in terms of safety and efficacy outcomes over a 3-year follow-up period.

Safety and efficacy of 6-month versus 12-month dual antiplatelet therapy in patients after implantation of multiple biodegradable polymer-coated sirolimus-eluting coronary stents: Insight from the I-LOVE-IT 2 trial.

OBJECTIVE: This study sought to compare the clinical outcomes of 6-month versus 12-month dual antiplatelet therapy (DAPT) in patients receiving multiple biodegradable polymer-coated sirolimus-eluting stents (BP-SES) implants. BACKGROUND: The clinical outcomes for patients who undergo multiple BP-SES implantation with different DAPT durations are uncertain. METHODS: In the I-LOVE-IT 2 trial, 907 patients treated with multiple BP-SES (total stent number ≥2) were assigned to receive 6-month (n = 440) or 12-month (n = 467) DAPT. The primary endpoint was 12-month target lesion failure (TLF), which is a composite of cardiac death, target vessel myocardial infarction (MI) or clinically indicated target lesion revascularization. The major secondary endpoints were 12-month net adverse clinical events, a composite of all causes of death, MI, stroke, any revascularization and bleeding. RESULTS: The number of stents per patient between the 6-month and 12-month DAPT group was similar (2.4 ± 0.7 vs. 2.4 ± 0.7, P = 0.47). The incidence of 12-month TLF was comparable in the 6-month and 12-month DAPT groups (9.3% vs.7.5%, Log-rank P = 0.33). However, landmark analysis showed that 12-month DAPT, compared to 6-month DAPT, was associated with a significantly lower risk of TLF (4.8% vs. 2.4%, Log-rank P = 0.049) at a cost of a slightly increased risk of all bleeding events (0.5% vs. 1.7%, Log-rank P = 0.07) between 6 and 12 months. CONCLUSIONS: In patients treated with multiple BP-SES, 6- and 12-month DAPT had similar impacts on 12-month clinical outcomes. Additionally, 12-month DAPT might reduce TLF between 6 and 12 months at the cost of a slightly increased risk of all bleeding events. © 2017 Wiley Periodicals, Inc.

Efficacy and safety of a biodegradable polymer Cobalt-Chromium sirolimus-eluting stent (EXCROSSAL) in treating de novo coronary artery disease: A pooled analysis of the CREDIT II and CREDIT III trials.

BACKGROUND: The safety and efficacy of the second-generation biodegradable polymer Cobalt-Chromium sirolimus-eluting stent (EXCEL2) in daily clinical practice remains unknown. Additionally, to meet the China Food and Drug Administration requirements, we conducted an objective performance criterion study from the CREDIT II and CREDIT III trials. METHODS: CREDIT II was a randomized trial comparing the EXCEL2 versus EXCEL stent in patients with up to 2 de novo coronary lesions. CREDIT III was a prospective, single-arm study evaluating the efficacy and safety of EXCEL2 in broad types of de novo coronary artery lesions. This pooled analysis included patients in the CREDIT III and EXCEL2 arm of the CREDIT II trial. The primary outcome was 12-month target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction (TV-MI), and clinical indicated target lesion revascularization (CI-TLR). The patient-oriented composite endpoint (PoCE) of all-cause death, all MI, or any revascularization was also analyzed. RESULTS: A total of 833 patients were included, consisting of 625 in the CREDIT III trial and 208 in the EXCEL2 arm of the CREDIT II trial. Twelve-month TLF occurred in 6.1% patients, cardiac death in 0.4%, TV-MI in 5%, and CI-TLR in 1.1%. Additionally, 64 (7.7%) PoCE and 3 probable late stent thromboses (0.4%) were recorded. CONCLUSION: EXCEL2 stent met the objective performance criterion on efficacy and safety with a low level of 12-month TLF as well as stent thrombosis when treating patients with de novo coronary lesions. © 2017 Wiley Periodicals, Inc.

Safety and efficacy of a novel abluminal groove-filled biodegradable polymer sirolimus-eluting stent for the treatment of de novo coronary lesions: two-year results from a prospective patient-level pooled analysis of TARGET trials.

OBJECTIVES: We aimed to evaluate the safety and effectiveness of the novel abluminal groove-filled biodegradable polymer-coated sirolimus-eluting FIREHAWK stent (MicroPort Medical, Shanghai, China) in a large cohort of patients. BACKGROUND: Trials on the FIREHAWK stent allowing targeted sirolimus release were not individually powered to reliably estimate low-frequency safety endpoints such as stent thrombosis (ST) or to examine long-term safety and efficacy. Additionally, the China Food and Drug Administration requires an objective performance criterion (OPC) study for new drug-eluting stents. METHODS: The primary endpoint, target lesion failure (TLF), was defined as the composite of cardiac death, target vessel myocardial infarction (MI), or clinically indicated target lesion revascularization at 12 months. Patient-level data from 1,007 patients with de novo native coronary lesions exclusively treated with the FIREHAWK stent in the TARGET serial studies (I and II) were prospectively collected, pooled and analyzed throughout a 2-year follow-up. RESULTS: The 12-month rate of TLF in 1,003 patients (follow-up rate, 99.6%) was 3.9% (upper 95% confidence interval (CI): 5.3%), which was significantly lower than the performance goal of 9.0% (P < 0.0001). The 24-month rates of TLF, PoCE (a composite of all-cause death, all MI, or any revascularization), and ARC definite or probable ST were 4.6%, 7.8% and 0.1%, respectively. In subgroup analysis, long lesion (≥ 30 mm) was an independent predictor of TLF within 2 years (hazard ratio [95%CI]: 2.44 [1.32, 4.53], P < 0.01). CONCLUSIONS: This pooled, patient-level analysis indicates that the FIREHAWK stent exhibits a promising 2-year efficacy and safety profile.

First-in-man study evaluating the safety and efficacy of a second generation biodegradable polymer sirolimus-eluting stent in the treatment of patients with de novo coronary lesions: clinical, Angiographic, and OCT outcomes of CREDIT-1.

OBJECTIVE: To evaluate the preliminary safety and efficacy of the EXCEL II stent system. BACKGROUND: Although the first biodegradable polymer drug-eluting stent (BP-DES), EXCEL, was launched nearly a decade ago, in-stent restenosis and stent thrombosis remain pertinent clinical problems in practice. A new cobalt-chromium BP-DES EXCEL II has been developed with the aim of improving stent safety and efficacy. METHODS: Forty-five patients with single de novo native coronary lesions were enrolled and randomized to two groups in a 2:1 ratio, the 4-month follow-up group (n = 30) and the 12-month follow-up group (n = 15). All patients underwent percutaneous coronary intervention (PCI) with the EXCEL II stent system. Quantitative coronary angiography (QCA) and optical coherence tomography (OCT) were used to assess coronary vasculature at the designated 4- or 12-month follow-up. The primary outcome was major adverse cardiac events (MACE) at 30 days post-PCI. RESULTS: No MACE, thrombotic events, or target lesion failure was found in the 45 patients during the 12-month follow-up. There was no significant difference (P > 0.05) between the two groups in terms of in-stent and in-segment late lumen loss (LLL). No in-stent and in-segment restenosis was found in either group. At follow-up, the ratio of >10% uncovered struts per lesion was 26.67% in the 4-month group and 0% in the 12-month group (P < 0.05). Neointimal coverage in the 12-month group was significantly better than in the 4-month group (98.58% vs. 93.51%, P < 0.01). CONCLUSIONS: This first-in-man study demonstrates promising feasibility, safety, and efficacy of EXCEL II stents. These stents were found to have rapid endothelialization and low LLL rates at 4 and 12 months after implantation.

Dual antiplatelet therapy over 6 months increases the risk of bleeding after biodegradable polymer-coated sirolimus eluting stents implantation: insights from the CREATE study.

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation remains controversial. The primary aim of our study was to evaluate the impact of optimal DAPT duration on bleeding events between 6 and 12 months after biodegradable polymer-coated DES implantation. The secondary aim is to determine the predictors and prognostic implications of bleeding. METHODS: This study is a post hoc analysis of the Multi-Center Registry of EXCEL Biodegradable Polymer Drug Eluting Stents (CREATE) study population. A total of 2,040 patients surviving at 6 months were studied, including 1,639 (80.3%) who had received 6-month DAPT and 401 (19.7%) who had received DAPT greater than 6 months. Bleeding events were defined according to the bleeding academic research consortium (BARC) definitions as described previously and were classified as major/minor (BARC 2-5) and minimal (BARC 1). A left censored method with a landmark at 6 months was used to determine the incidence, predictors, and impact of bleeding on clinical prognosis between 6 and 12 months. RESULTS: At 1-year follow-up, patients who received prolonged DAPT longer than 6 months had a significantly higher incidence of overall (3.0% vs. 5.5%, P = 0.021) and major/minor bleeding (1.1% vs. 2.5%, P = 0.050) compared to the patients who received 6-month DAPT. Multivariate analysis showed that being elderly (OR = 1.882, 95% CI: 1.109-3.193, P = 0.019), having diabetes (OR = 1.735, 95% CI: 1.020-2.952, P = 0.042), having a history of coronary artery disease (OR = 2.163, 95% CI: 1.097-4.266, P = 0.026), and duration of DAPT longer than 6 months (OR = 1.814, 95% CI: 1.064-3.091, P = 0.029) were independent predictors of bleeding. Patients with bleeding events had a significantly higher incidence of cardiac death, myocardial infarction, target lesion revascularization, and stent thrombosis. CONCLUSIONS: Prolonged DAPT (greater than 6 months) after biodegradable polymer-coated DES increases the risk of bleeding, and is associated with adverse cardiac events at 1-year follow-up. (J Interven Cardiol 2014;27:119-126).

Clinical efficacy and safety of biodegradable polymer-based sirolimus-eluting stents in patients with diabetes mellitus insight from the 4-year results of the create study.

BACKGROUND: Diabetes mellitus is an independent predictor of adverse clinical events after drug-eluting stent implantation. OBJECTIVES: The objective of this study is to evaluate the long-term clinical efficacy and safety of biodegradable polymer-based sirolimus-eluting stents in diabetic versus non-diabetic patients. METHODS: A total of 2077 "all comers," including 440 (21.2%) diabetic patients and 1637 (78.8%) non-diabetic patients, were prospectively enrolled in the CREATE study at 59 centers in four countries. The recommended antiplatelet regimen was clopidogrel and aspirin for 6 months followed by chronic aspirin therapy. The primary outcome was the rate of major adverse cardiac events (MACE), defined as a composite of cardiac death, non-fatal myocardial infarction (MI), and target lesion revascularization (TLR). RESULTS: Diabetic patients had higher risks of all-cause death (8.2% vs. 3.4%, P < 0.001) and cardiac death (4.1% vs. 1.4%, P < 0.001) compared with non-diabetic patients at 4 years. The rates of non-fatal MI (0.2% vs. 0.9%, P = 0.218), TLR (2.0% vs. 2.8%, P = 0.357), MACE (5.9% vs. 4.4%, P = 0.227), and overall stent thrombosis (1.6% vs. 1.6%, P = 0.932) were not significantly different between diabetic and non-diabetic patients. A landmark analysis showed that prolonged clopidogrel therapy (>6 months) was not beneficial in reducing the cumulative hazards of MACE either in diabetic or non-diabetic patients (log rank P = 0.810). CONCLUSIONS: Biodegradable polymer-based sirolimus-eluting stents for the treatment of diabetic patients had a similar clinical event rate at 4 years compared with non-diabetic patients, except for a higher mortality rate.

Effect of branched polyethyleneimine and citric acid on the structural, physical and antibacterial properties of corn starch/chitosan films.

To improve the antibacterial and physical properties of corn starch/chitosan films effectively, starch/chitosan/polyethyleneimine (PEI) blend films crosslinked by citric acid (labeled SCPC) with different contents (2.5 %, 5.0 %, 7.5 % and 10.0 %) were prepared by the solution casting method. The films were characterized in detail. The results showed that the addition of 3.75 % PEI improved the tensile strength and elongation at break of the starch/chitosan film simultaneously, but the thermal stability decreased. After CA was incorporated, the tensile strength and thermal stability of the films were enhanced significantly. FTIR, XRD, and 1H NMR analyses revealed strong interactions among CA, PEI and starch-chitosan. All films showed smooth and homogenous fragile cross-sections. The water vapor permeability of the film decreased overall after PEI and CA addition. Moisture uptake (MU) accelerated after PEI addition, but the balanced MU was reduced by CA cross-linking. All films showed an inhibitory effect on E. coli and S. aureus, and CA incorporation significantly improved the inhibition ability of the film. The SCPC film with 3.75 % PEI and 5.0 % CA addition has the best comprehensive properties, which endowed its application in the bioactive packaging field.

Engineering Immunomodulatory Stents Using Zinc Ion-Lysozyme Nanoparticle Platform for Vascular Remodeling.

Rapid endothelialization of cardiovascular materials can enhance the vascular remodeling performance. In this work, we developed a strategy for amyloid-like protein-assembly-mediated interfacial engineering to functionalize a biomimetic nanoparticle coating (BMC). Various groups (e.g., hydroxyl and carboxyl) on the BMC are responsible for chelating Zn2+ ions at the stent interface, similar to the glutathione peroxidase-like enzymes found in vivo. This design could reproduce the release of therapeutic nitric oxide gas (NO) and an aligned microenvironment nearly identical with that of natural vessels. In a rabbit abdominal aorta model, BMC-coated stents promoted vascular healing through rapid endothelialization and the inhibition of intimal hyperplasia in the placement sites at 4, 12, and 24 weeks. Additionally, better anticoagulant activity and immunomodulation in the BMC stents were also confirmed, and vascular healing was mainly dependent on cell signaling through the cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) cascade. Overall, a metal-polypeptide-coated stent was developed on the basis of its detailed molecular mechanism of action in vascular remodeling.

Five-year outcomes of biodegradable versus second-generation durable polymer drug-eluting stents used in complex percutaneous coronary intervention.

BACKGROUND: There are few data comparing clinical outcomes of complex percutaneous coronary intervention (CPCI) when using biodegradable polymer drug-eluting stents (BP-DES) or second-generation durable polymer drug-eluting stents (DP-DES). The purpose of this study was to investigate the safety and efficacy of BP-DES and compare that with DP-DES in patients with and without CPCI during a 5-year follow-up. METHODS: Patients who exclusively underwent BP-DES or DP-DES implantation in 2013 at Fuwai Hospital were consecutively enrolled and stratified into two categories based on CPCI presence or absence. CPCI included at least one of the following features: unprotected left main lesion, ≥2 lesions treated, ≥2 stents implanted, total stent length >40 mm, moderate-to-severe calcified lesion, chronic total occlusion, or bifurcated target lesion. The primary endpoint was major adverse cardiac events (MACE) including all-cause death, recurrent myocardial infarction, and total coronary revascularization (target lesion revascularization, target vessel revascularization [TVR], and non-TVR) during the 5-year follow-up. The secondary endpoint was total coronary revascularization. RESULTS: Among the 7712 patients included, 4882 (63.3%) underwent CPCI. Compared with non-CPCI patients, CPCI patients had higher 2- and 5-year incidences of MACE and total coronary revascularization. Following multivariable adjustment including stent type, CPCI was an independent predictor of MACE (adjusted hazard ratio [aHR]: 1.151; 95% confidence interval [CI]: 1.017-1.303, P  = 0.026) and total coronary revascularization (aHR: 1.199; 95% CI: 1.037-1.388, P  = 0.014) at 5 years. The results were consistent at the 2-year endpoints. In patients with CPCI, BP-DES use was associated with significantly higher MACE rates at 5 years (aHR: 1.256; 95% CI: 1.078-1.462, P  = 0.003) and total coronary revascularization (aHR: 1.257; 95% CI: 1.052-1.502, P  = 0.012) compared with that of DP-DES, but there was a similar risk at 2 years. However, BP-DES had comparable safety and efficacy profiles including MACE and total coronary revascularization compared with DP-DES in patients with non-CPCI at 2 and 5 years. CONCLUSIONS: Patients underwent CPCI remained at a higher risk of mid- to long-term adverse events regardless of the stent type. The effect of BP-DES compared with DP-DES on outcomes was similar in CPCI and non-CPCI patients at 2 years but had inconsistent effects at the 5-year clinical endpoints.

Sustained clinical safety and efficacy of a biodegradable-polymer coated sirolimus-eluting stent in "real-world" practice: three-year outcomes of the CREATE (Multi-Center Registry of EXCEL Biodegradable Polymer Drug Eluting Stents) study.

BACKGROUND: The CREATE is a post-marketing surveillance multicenter registry that demonstrated satisfactory angiographic and clinical (at 18 months) outcomes of a biodegradable polymer based sirolimus-eluting stent (EXCEL, JW Medical System, Weihai, China) for the treatment of patients in routine clinical practice. OBJECTIVES: To evaluate the three-year clinical safety and efficacy outcomes in patients enrolled in the CREATE study. METHODS: A total of 2077 all comers have been enrolled in the CREATE study at 59 centers from four countries. Recommended antiplatelet regimen was clopidogrel and aspirin for six months followed by chronic aspirin therapy. The prespecified primary outcome was the rate of major adverse cardiac events (MACE) at 12, 18, and 36 months. RESULTS: Clinical follow-up was completed in 2025 (97.5%) patients at three years. The average duration of clopidogrel treatment was 199.8 ± 52.7 days and 80.5% of discharged patients discontinued clopidogrel at six months. The cumulative rate of MACE was 4.5% and the rate of stent thrombosis was 1.53% at three years. At six months to three years, prolonged clopidogrel therapy (>6 months) was not beneficial in reducing cumulative hazards of MACE (3.4% vs. 3.1%, log rank P = 0.725) or stent thrombosis (1.5% vs. 0.6%, log rank P = 0.053). CONCLUSIONS: This study demonstrates sustained three-year clinical safety and efficacy of biodegradable polymer-based sirolimus-eluting stents when used with six months of dual antiplatelet therapy in a "real-world" setting.

Biolimus-Coated Balloon in Small-Vessel Coronary Artery Disease: The BIO-RISE CHINA Study.

BACKGROUND: Drug-coated balloons are a safe and effective option for patients undergoing percutaneous coronary intervention, but prior randomized studies have exclusively used paclitaxel-coated devices. OBJECTIVES: The aim of this study was to assess for the first time the safety and efficacy of a novel biolimus-coated balloon (BCB) in patients with small-vessel coronary disease. METHODS: In a prospective trial conducted at 10 centers in China, 212 patients with small-vessel native coronary disease (reference vessel diameter 2.0-2.75 mm, lesion length ≤25 mm) were randomized to receive a BCB or an uncoated balloon. The primary endpoint was in-segment late lumen loss at 9 months. RESULTS: In the per-protocol population, angiographic late lumen loss at 9 months was 0.16 ± 0.29 mm in the BCB group vs 0.30 ± 0.35 mm with the plain balloon (P = 0.001). Late luminal enlargement (positive remodeling) occurred in 29.7% of patients in the BCB group vs 9.8% of patients with plain balloons (P = 0.007). In the full analysis set population, after 12 months, target lesion failure rates were 6.7% in the BCB group vs 13.9% with the plain balloon (HR: 0.47; 95% CI: 0.19-1.16), and rates of the patient-oriented clinical outcome were 14.3% with the BCB vs 21.8% with the plain balloon (HR: 0.64; 95% CI: 0.33-1.24). CONCLUSIONS: In this first-in-human study, a novel BCB showed superior efficacy to plain balloon angioplasty in patients with small-vessel coronary disease undergoing percutaneous coronary intervention. Positive vascular remodeling was more frequent, and there was a trend toward improved clinical outcomes. (A Randomized Trial of a Biolimus-Coated Balloon Versus POBA in Small Vessel Coronary Artery Disease [Brave]; NCT03769623).

Biodegradable polymer-coated versus durable polymer-coated sirolimus-eluting stents: the final 5-year outcomes of the I-LOVE-IT 2 trial.

AIMS: This analysis presents the final five-year results of the I-LOVE-IT 2 trial, a non-inferiority study comparing a biodegradable polymer (BP) sirolimus-eluting stent (SES) with a durable polymer (DP) SES in patients with coronary artery disease. METHODS AND RESULTS: Overall, 2,737 Chinese patients eligible for coronary stenting were treated with BP-SES or DP-SES in a 2:1 ratio. Patients who were randomised to the BP-SES group were additionally re-randomised to receive either six-month or 12-month dual antiplatelet therapy (DAPT) in a 1:1 ratio. The primary endpoint was 12-month target lesion failure (TLF: cardiac death, target vessel myocardial infarction (MI), or clinically indicated target lesion revascularisation). At five years, the overall follow-up rate was 90.8%, and the cumulative incidence of TLF as the primary endpoint was similar between BP-SES and DP-SES (hazard ratio [HR] 1.01, 95% confidence interval [CI]: 0.79 to 1.28), as was that for the patient-oriented composite endpoint (PoCE: all-cause death, all MI and any revascularisation) (HR 1.03, 95% CI: 0.86 to 1.23), or definite/probable stent thrombosis (ST) (HR 0.91, 95% CI: 0.70 to 1.77). Cumulative events were also similar between the six-month DAPT and 12-month DAPT groups after BP-SES implantation. CONCLUSIONS: I-LOVE-IT 2 showed that the five-year safety and efficacy of BP-SES and DP-SES were similar, as were those between six months and 12 months of DAPT after BP-SES implantation.

Comparison of the Ultrathin Strut, Biodegradable Polymer Sirolimus-eluting Stent With a Durable Polymer Everolimus-eluting Stent in a Chinese Population: The Randomized BIOFLOW VI Trial.

PURPOSE: The BIOFLOW-VI (Biotronik-Safety and Clinical Performance of the Drug Eluting Orsiro Stent in the Treatment of Subjects With De Novo Coronary Artery Lesions-VI) study evaluates the angiographic efficacy, clinical safety, and effectiveness of the ultrathin strut, biodegradable polymer sirolimus-eluting stent (BP-SES) compared with a durable polymer everolimus-eluting stent (DP-EES). This randomized controlled clinical trial was designed to enable approval of new drug-eluting stents in China. METHODS: A total of 440 eligible patients from 11 sites with up to 2 de novo native coronary artery lesions were randomly assigned to receive either BP-SES (n = 220) or DP-EES (n = 220) from July 2014 to September 2016 in this prospective, multicenter, noninferiority trial. FINDINGS: The primary end point of 9-month in-stent late lumen loss (LLL) was 0.05 (0.02) mm in the BP-SES group versus 0.07 (0.02) mm in the DP-EES group, with a mean difference of -0.02 mm (95% CI, -0.06 to 0.03; P = 0.44; Pnoninferiority < 0.0001). At 1 year, the target lesion failure rate (cardiac death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization) was similar between the 2 groups (BP-SES 2.3% vs DP-EES 1.4%; P = 0.50). No definite or probable stent thrombosis had occurred in any of the 2 treatment arms. IMPLICATIONS: The randomized BIOFLOW-VI trial showed that BP-SES was noninferior to DP-EES with regard to the primary end point of 9-month in-stent LLL in a Chinese population. ClinicalTrials.gov Identifier: NCT02870985.

Long-term clinical, angiographic, and intravascular ultrasound outcomes of biodegradable polymer-coated sirolimus-eluting stents.

BACKGROUND: The residual drug carriers on drug-eluting stents (DES) surfaces are considered to be one of the most significant reasons causing late thrombosis. There is no documented data currently available on the safety/benefit profile beyond 6 months of EXCEL stent, a novel sirolimus-eluting stent with biodegradable polymer coating, in treating patients with coronary artery disease (CHD). OBJECTIVE: To evaluate the long-term efficacy and safety of EXCEL stent on treating CHD patients. METHODS: Between February and March 2006, a consecutive cohort of complex patients treated with the EXCEL stent was prospectively enrolled in this single-center registry. Antiplatelet protocol was 6-month dual antiplatelet therapy with clopidogrel and aspirin followed by aspirin alone indefinitely. The primary outcome was major adverse cardiac events (MACE) at 12 months. Secondary outcomes included in-segment and in-stent late lumen loss and binary restenosis rate measured by quantitative coronary angiography (QCA) analysis at 8 months postindex PCI procedure. RESULTS: A total of 100 patients with 153 lesions were included in this analysis. Most lesions (83.0%) were classified as complex (B2/C). At 12 months, four patients (4.0%) experienced MACE, which were four target-lesion revascularizations due to in-stent restenosis (ISR). All patients received follow-up up to 24 +/- 0.4 months and no cardiac death, MI, and in-stent thrombosis occurred during the 6 months of dual antiplatelet therapy or the subsequent 15 months of aspirin treatment alone. QCA analysis of 112 lesions from 75 patients showed 3.6% (4/112) in-stent lesion restenosis, 5.4% (6/112) in-segment lesion restenosis, 0.12 +/- 0.34 mm in-stent late lumen loss, and 0.08 +/- 0.35 mm in-segment late lumen loss. CONCLUSIONS: In this single-center experience with complex patients and lesions, the EXCEL stent implantation with 6-month dual antiplatelet treatment proved to markedly reduce the incidence of 24-month ISR and MACE. These preliminary findings require further validation by large scale, randomized trials.

A Randomized Trial Comparing the NeoVas Sirolimus-Eluting Bioresorbable Scaffold and Metallic Everolimus-Eluting Stents.

OBJECTIVES: The authors sought to evaluate the safety and effectiveness of the NeoVas bioresorbable scaffold (BRS) compared with metallic drug-eluting stents. BACKGROUND: BRS have the potential to improve very late outcomes compared with metallic drug-eluting stents, but some BRS have been associated with increased rates of device thrombosis before complete bioresorption. NeoVas is a new poly-l-lactic acid BRS that elutes sirolimus from a poly-D, l-lactide coating. METHODS: Eligible patients with a single de novo native coronary artery lesion with a reference vessel diameter 2.5 to 3.75 mm and a lesion length ≤20 mm were randomized 1:1 to NeoVas BRS versus cobalt-chromium everolimus-eluting stents (CoCr-EES). Angiographic follow-up was performed in all patients at 1 year. The primary endpoint was angiographic in-segment late loss (LL), and the major secondary endpoint was the rate of angina. Baseline and follow-up optical coherence tomography and fractional flow reserve were performed in a pre-specified subgroup of patients. RESULTS: The authors randomized 560 patients at 32 centers to treatment with NeoVas (n = 278) versus CoCr-EES (n = 282). One-year in-segment LL with NeoVas and CoCr-EES were 0.14 ± 0.36 mm versus 0.11 ± 0.34 mm (difference 0.03 mm; upper 1-sided 97.5% confidence interval 0.09 mm; pnoninferiority < 0.0001; psuperiority = 0.36). Clinical outcomes at 1 year were similar in the 2 groups, as were the rates of recurrent angina (27.9% vs. 32.1%; p = 0.26). Optical coherence tomography at 1 year demonstrated a higher proportion of covered struts (98.7% vs. 96.2%; p < 0.001), less strut malapposition (0% vs. 0.6%; p <0.001), and a smaller minimal lumen area (4.71 ± 1.64 vs. 6.00 ± 2.15 mm2; p < 0.001) with NeoVas compared with CoCr-EES respectively, with nonsignificant differences in fractional flow reserve (0.89 ± 0.08 vs. 0.91 ± 0.06; p = 0.07). CONCLUSIONS: The NeoVas BRS was noninferior to CoCr-EES for the primary endpoint of 1-year angiographic in-segment LL, and resulted in comparable 1-year clinical outcomes, including recurrent angina. (NeoVas Bioresorbable Coronary Scaffold Randomized Controlled Trial; NCT02305485).

Five-year outcomes of ST-elevation myocardial infarction versus non-ST-elevation acute coronary syndrome treated with biodegradable polymer-coated sirolimus-eluting stents: Insights from the CREATE trial.

BACKGROUND: Long-term outcome of drug-eluting stents (DES) for ST-elevation myocardial infarction (STEMI) versus non-ST-elevation acute coronary syndrome (NSTE-ACS) remains unclear. This study sought to compare the long-term outcomes of biodegradable polymer-coated DES in patients with STEMI versus NSTE-ACS. METHODS: We explored a post hoc analysis of the 5-year outcome of the CREATE trial in the subgroup of patients with STEMI (n=318) versus NSTE-ACS (n=1223) who were implanted with biodegradable polymer-coated DES. The primary outcome was the rate of major adverse cardiac events (MACE) at 5 years. Clopidogrel and aspirin for 6 months followed by chronic aspirin therapy were recommended. RESULTS: STEMI patients showed a trend of increase in MACE (8.7% vs. 6.8%, log rank p=0.289) compared to NSTE-ACS patients at 5 years, and a greater risk of cardiac death (5.4% vs. 2.1%, log rank p=0.003), mainly driven by the higher cardiac death rate within the first month after stent placement (log rank p=0.003) and the last year of follow-up (log rank p=0.001). No significant difference in stent thrombosis was found between them (3.1% vs. 2.5%, log rank p=0.653). Prolonged clopidogrel therapy (>6 months) showed no effect on risk of MACE or stent thrombosis between the two groups (both p for interaction >0.1). CONCLUSIONS: STEMI patients have a higher risk of cardiac mortality compared with NSTE-ACS patients after biodegradable polymer-coated DES placement, primarily attribute to more cardiac deaths that happened within the first month after the event and the last year of follow-up.

A randomised comparison of biodegradable polymer- and permanent polymer-coated platinum-chromium everolimus-eluting coronary stents in China: the EVOLVE China study.

AIMS: The EVOLVE China randomised study sought to evaluate the clinical safety and effectiveness of the SYNERGY bioabsorbable polymer-coated everolimus-eluting stent (EES) for the treatment of patients with coronary heart disease in China. METHODS AND RESULTS: Eligible patients with de novo native coronary artery lesions were randomised (1:1) to receive the SYNERGY or PROMUS Element Plus stent. The primary endpoint was in-stent late loss at nine months. Secondary endpoints included death, MI, revascularisation, and stent thrombosis up to 12 months. A total of 412 subjects were randomised (205 SYNERGY; 207 PROMUS Element Plus) at 14 sites in China from October 2013 to July 2014. SYNERGY was non-inferior to PROMUS Element Plus for the primary endpoint of nine-month in-stent late loss: SYNERGY 0.20±0.33 mm vs. PROMUS Element Plus 0.17±0.38 mm with an upper one-sided 97.5% confidence interval of the difference (0.10 mm), significantly less than the non-inferiority margin (0.15 mm; p<0.0008). Clinical adverse event rates were low and not significantly different between groups at nine and 12 months (all p>0.05). CONCLUSIONS: In the EVOLVE China trial, the SYNERGY bioabsorbable polymer-coated EES was noninferior to the PROMUS Element Plus permanent polymer-coated EES for the primary endpoint of late loss at nine months.