Clinical outcomes in 2481 unselected real-world patients treated with a polymer-free sirolimus-eluting stent: 3 years results from the NANO multicenter Registry.

OBJECTIVES: To evaluate the 3-year clinical outcomes of a polymer-free sirolimus-eluting, Nano plus stent for the treatment of coronary artery disease in the NANO multicenter Registry. BACKGROUND: The long-term clinical data evaluating the safety and efficacy of the novel polymer-free sirolimus-eluting Nano plus stent (Lepu Medical, Beijing, China) is limited. METHODS: The NANO all-comers Registry trial was a prospective, multicenter clinical registry conducted in 26 centers in China between August 2016 and January 2017. A total of 2481 consecutive patients were exclusively treated with the Nano plus stent. The primary clinical endpoint, target lesion failure (TLF, defined as cardiac death, target vessel nonfatal myocardial infarction, and clinically driven target lesion revascularization [CD-TLR]), was analyzed at 3 years. RESULTS: At 3 years, 2295 patients (92.5%) were followed. The incidence of TLF was 6.8% (168/2481). The rate of cardiac death was 3.8% (94/2481), target vessel nonfatal myocardial infarction 0.7% (18/2481), and CD-TLR 2.9% (68/2481). The rate of definite/probable stent thrombosis was 0.5% (13/2481). The risk factors of diabetes mellitus, acute myocardial infarction, age, chronic renal failure, in-stent restenosis, chronic total occlusion, and left ventricular ejection fraction < 40% were the independent predictors of 3-year TLF. CONCLUSIONS: At three years, the rate of TLF was relatively low in patients treated with the polymer-free Nano plus stent. The polymer-free Nano plus stent showed a favorable safety and efficacy profile in real-world patients. Clinical trial registration URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT02929030.

One-year clinical results of the NANO registry: A multicenter, prospective all-comers registry study in patients receiving implantation of a polymer-free sirolimus-eluting stent.

OBJECTIVES: We aimed to evaluate the safety and efficacy of Nano+™ (Lepu Medical, Beijing, China) stent implantation in all-comer patients at the 1-year follow-up. BACKGROUND: The Nano+™ stent is a novel polymer-free sirolimus-eluting stent polymer that employs nanoporous stent surface technology to control drug-delivery. The Nano+™ stent is one of the most widely used drug-eluting stent (DES) in China. METHODS: A total of 2,481 consecutive patients were included in the multicenter and prospective NANO registry. In this study, the primary endpoint was target lesion failure (TLF) at 1-year follow-up, defined as a composite of cardiac death, target vessel nonfatal myocardial infarction (TV-MI), and clinically driven target lesion revascularization (TLR). The safety endpoint was the occurrence of definite or probable stent thrombosis (ST). RESULTS: Up to 40.2% of patients presented with acute myocardial infarction (AMI). A total of 63.9% of the 2,904 lesions were American College of Cardiology/American Heart Association (ACC/AHA) type B2 or C lesions. One-year follow-up data were available for 98.4% of patients. The 1-year rate of TLF was 3.1% with rates of 1.3, 1.8, and 0.4% for clinically driven TLR, cardiac death, and TV-MI, respectively. ST occurred in 0.4% of patients. Diabetes mellitus, AMI, left ventricular ejection fraction <40% and long lesions (>40 mm) were independent predictors of 1-year TLF. CONCLUSIONS: The 1-year clinical outcomes were excellent for Nano+™ polymer-free SES implantation in an all-comer patient population. Follow-up will be extended up to 5 years, to further elucidate the potential long-term clinical benefits. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02929030.

Polymer-free drug-eluting stents for coronary artery disease.

Polymer-free drug-eluting stents (PF-DES) were designed with the expectation of avoiding late restenosis and thrombosis related to the polymer used in traditional DES platforms. Furthermore, due to similarities with bare metal stents after drug elution, PF-DES has been considered as particularly suitable for patients at high bleeding risk. A variety of PF-DES platforms have been clinically tested. Despite their theoretical advantages, PF platforms showed comparable clinical outcomes with modern permanent- or biodegradable polymer-based DES up to 5 years after implantation. Use of more biocompatible polymers on the modern DES platforms is one of the reasons therefore. Their improved safety profile allows already less intensive antithrombotic regimes after DES. Hence, nowadays PF-DES platforms can be considered as one of many DES options for percutaneous treatment of coronary artery disease.

Five-year clinical outcome of multicenter randomized trial comparing amphilimus - with paclitaxel-eluting stents in de novo native coronary artery lesions.

OBJECTIVES: Long-term data from randomized studies on polymer-free stents are scarce. Long-term data of Cre8 amphilimus eluting stent are still not available. We sought to investigate contribution of a polymer-free design versus a permanent-polymer one on the long-term. METHODS AND RESULTS: Patients undergoing percutaneous coronary intervention for de novo lesions were randomized 1:1 to Cre8 or Taxus Liberté (323 overall, 126 Cre8). Original primary endpoint (6-month angiographic in-stent late lumen loss) already demonstrated the superiority of Cre8 vs Taxus (0.14 + 0.36 mm vs. 0.34 + 0.40 mm; p < 0.001). Secondary endpoints were the device oriented composite endpoint (DOCE), patient oriented composite endpoint (POCE) up to 5-year. Long-term follow-up data confirmed the superiority shown by Cre8 in the analysis of the angiographic endpoint at 6-month, especially in the diabetic patients, where the device strongly reduced the clinical difference with non-diabetic. Landmark analysis demonstrated that the incidence of DOCE after 1-year and up to 5-year follow up was significantly lower in patients implanted with Cre8 AES (2.1% Cre8 vs. 9.3% Taxus, p = 0.009). While no differences were found in terms of DOCE rate among diabetic and non-diabetic patients treated with the Cre8 AES (HR 1.039; 95%CI 0.320-3.374), this was not true for Taxus (HR 2.64; 95%CI 1.112-6.278). CONCLUSIONS: Cre8 showed favourable safety and efficacy results versus Taxus at 5-years follow-up, with a superior clinical performance for the DOCE endpoint from 1 to 5 years. Cre8, differently from Taxus, has been able to strongly reduce the differences in clinical outcome between diabetic and non-diabetic up to 5 years, suggesting the higher efficacy of Cre8 in the treatment of diabetic patients.

Modelling drug release from polymer-free coronary stents with microporous surfaces.

Traditional coronary drug-eluting stents (DES) are made from metal and are coated with a permanent polymer film containing an anti-proliferative drug. Subsequent to stent deployment in a diseased coronary artery, the drug releases into the artery wall and helps prevent restenosis by inhibiting the proliferation of smooth muscle cells. Although this technology has proven to be remarkably successful, there are ongoing concerns that the presence of a polymer in the artery can lead to deleterious medical complications, such as late stent thrombosis. Polymer-free DES may help overcome such shortcomings. However, the absence of a rate-controlling polymer layer makes optimisation of the drug release profile a particular challenge. The use of microporous stent surfaces to modulate the drug release rate is an approach that has recently shown particularly promising clinical results. In this study, we develop a mathematical model to describe drug release from such stents. In particular, we develop a mathematical model to describe drug release from microporous surfaces. The model predicts a two-stage release profile, with a relatively rapid initial release of most of the drug, followed by a slower release of the remaining drug. In the model, the slow release phase is accounted for by an adsorption/desorption mechanism close to the stent surface. The theoretical predictions are compared with experimental release data obtained in our laboratory, and good agreement is found. The valuable insights provided by our model will serve as a useful guide for designing the enhanced polymer-free stents of the future.

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.

From drug eluting stents to bioresorbable scaffolds; to new horizons in PCI.

Drug eluting stents and particularly the fully bioresorbable drug-eluting scaffolds herald a new era in percutaneous treatment of coronary artery disease. There has been tremendous progress in drug eluting stents with fully biodegradable coating polymers and polymer-free devices with reservoir technology planting the anti-proliferative drug. Despite significant decreases in in-stent restenosis rates with drug eluting stents, limitations still remain before we are able to develop fully bioresorbable scaffolds. Enhanced mechanical flexibility that provides superior conformability to the vessel wall, resumption of the vasoreactivity in the follow-up period and improving visualization on non-invasive imaging modalities are some of the supremacies of the fully bioresorbable scaffolds. In this review, we aim to give a general view on the latest developments in metallic drug eluting stents and fully bioresorbable scaffolds.

Patient-tailored Drug-eluting Stent Choice - A Solution for Patients with Diabetes: Proceedings of Two Satellite Symposia Held at EuroPCR in May 2015 in Paris.

Although second-generation drug-eluting stents (DES) have improved outcomes in percutaneous coronary interventions (PCIs), important unmet needs remain. Two symposia at EuroPCR 2015 focused on two challenging scenarios. First, patients with diabetes mellitus (DM) have generally inferior outcomes following PCI. The Cre8™ stent (manufactured by CID Spa, member of Alvimedica Group) has shown unique efficacy in subpopulations of patients with DM during clinical trials. A live case in a patient with diabetes illustrated the challenges of complex multivessel disease. Second, optimising stent selection towards devices that have demonstrated complete and early endothelialisation offers the potential to reduce the duration of dual antiplatelet therapy. The Cre8™ DES features a polymer-free platform and has been associated with low rates of in-stent thrombosis.

Cre8™ Unique Technology in Challenging Daily Practice: Proceedings of a satellite symposium held at EuroPCR on 20th - 23rd May 2014 in Paris.

The use of drug-eluting stents (DES) has improved clinical outcomes in percutaneous coronary intervention (PCI) procedures. However, first-generation DES were associated with safety concerns arising from the persistence of durable polymers, including late stent thrombosis. The Cre8™ DES is a novel polymer-free stent designed to overcome these issues. In a presentation at EuroPCR 2014, two clinical cases were discussed. The first was a case of high bleeding risk; the second was the case of multivessel disease with a significant risk of stent restenosis. Together, these cases illustrated the complexity of decision-making in PCI in daily practice. In both cases, the Cre8™ DES offered a safe and effective solution to these challenging cases.

Meeting the Unmet - The Cre8 Polymer-free Drug-eluting Stents Technology: Proceedings of a satellite symposium held at EuroPCR on May 20th - 23rd 2014 in Paris.

The use of first-generation drug-eluting stents (DES) has been associated with safety concerns such as very late stent thrombosis. Today, with the release of newer DES, there is a need for comparative studies of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) to demonstrate their value in patients with high risk of restenosis such as diabetic patients. In a satellite symposium presented at EuroPCR 2014, the Cre8™ DES was discussed. The Cre8 device has a number of unique clinical features, including polymer-free technology, abluminal reservoir technology and bio-inducer surface that ensure effective neointima suppression and rapid endothelialisation. The efficacy of the Cre8 DES has been demonstrated in the International randomised comparison between DES Limus Carbostent and Taxus drug-eluting stents in the treatment of de novo coronary lesions (NEXT) randomised clinical study, with equivalent efficacy in the diabetic and general populations, a unique finding. Ongoing clinical studies such as Investig8 and the Tel Aviv Medical Center (TLVMC) Cre8 study have confirmed the efficacy of the device in patient populations with a high proportion of diabetic patients. The Demonstr8 randomised trial has shown almost complete Cre8 strut coverage at three months with a numerical advantage versus bare metal stent (bare metal stents [BMS] - comparator device) at one month. In addition, use of the Cre8 DES may enable a shorter duration of dual antiplatelet therapy (DAPT) following PCI. The Cre8 DES therefore represents a significant advance in stent technology and may be particularly useful in challenging clinical settings.