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.

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.

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).

Alginate-calcium microsphere loaded with thrombin: a new composite biomaterial for hemostatic embolization.

To date, transcatheter arterial embolization (TAE) has become a standard treatment to control intracavitary bleeding as an alternative to surgery. Due to excellent biocompatibility and no residual in vivo, biodegradable materials are preferred in TAE. However, gelfoam is the only commercially available biodegradable embolic material used to treat blunt trauma of solid abdominal viscera until now, and controversial on its stability and reliability never stopped in the past five decades. In this study, a new biodegradable macromolecule material (thrombin-loaded alginate-calcium microspheres, TACMs) was prepared using electrostatic droplet techniques and a special method was developed for hemostatic embolization. Thrombin was successfully loaded into microspheres with high encapsulation efficiency and drug loading capacity. A burst release of TACMs was observed at early stage and sustained release later on, with the activity of thrombin preserved well. The strength of TACMs mixed thrombus, which was used as embolic agent, increased in a dose-dependent manner after TACMs were added. In addition, the TACMs were verified to be of no cytotoxicity and systemic toxicity, and biodegradable in vivo. Finally, the results of preliminary applications revealed that the TACMs could serve as an effective and promising embolic material for blunt trauma and hemorrhage of solid abdominal viscera.