key: cord-0029489-fg8iny45
authors: Cornelissen, Anne; Sakamoto, Atsushi; Sato, Yu; Kawakami, Rika; Mori, Masayuki; Kawai, Kenji; Kutyna, Matthew; Fernandez, Raquel; Ghosh, Saikat; Barakat, Mark; Virmani, Renu; Finn, Aloke
title: COBRA PzF™ coronary stent in clinical and preclinical studies: setting the stage for new antithrombotic strategies?
date: 2021-09-15
journal: nan
DOI: 10.2217/fca-2021-0057
sha: 38b2af520ffab740df484a6c23f20d8162dfeb41
doc_id: 29489
cord_uid: fg8iny45

Major advances have been made in coronary artery stent technology over the last decades. Drug-eluting stents reduced in-stent restenosis and have shown better outcomes compared with bare metal stents, yet some limitations still exist to their use. Because they delay healing of the vessel wall, longer dual antiplatelet therapy is mandatory to mitigate against stent thrombosis and this limitation is most concerning in subjects at high risk for bleeding. The COBRA PzF nanocoated coronary stent has been associated with accelerated endothelialization relative to drug-eluting stents, reduced inflammation and thromboresistance in preclinical studies, suggesting more flexible dual antiplatelet therapy requirement with potential benefits especially in those at high bleeding risk. Here, we discuss the significance of COBRA PzF in light of recent experimental and clinical studies.

. The COBRA PzF nanocoated stent system. COBRA PzF is a coronary stent device characterized by ultrathin (71 μm) cobalt-chromium struts, coated by a nanothin (≤50 nm thickness) layer of Polyzene-F R with a modified open cell design. Reproduced with permission from CeloNova (https://celonova.com/cobra-pzf-nanocoated-stent/). on a rapid-exchange balloon delivery catheter and is available in sizes ranging from 2.5 to 4.0 mm in diameter and 8-30 mm in length.

PzF (poly[bis[trifluoroethoxy]phosphazene) polymer is a soft rubber-like inorganic, high molecular weight fluoropolymer that possesses a backbone of alternating nitrogen and phosphorus atoms and trifluoroethoxy side groups [24] . Early work by Welle et al. showed PzF coating results in hydrophobic surface properties, causing high adsorption of serum albumin, but low adsorption of fibronectin and fibrinogen [25] . PzF polymer is stable in contact with blood and retains its mechanical properties over at least 24 months [24] . In addition, the trifluoroethanol component is known to have anti-inflammatory properties and to stabilize proteins in solution against thermal denaturation [26] . In pilot experiments by Richter et al., PzF polymer surface modification of vascular stents improved thromboresistance and reduced late ISR compared with BMS in a rabbit iliac artery model [26] . Likewise, PzFnanocoated CoCr stents implanted in the right coronary artery of 30 mini-pigs showed a significantly lower average loss in lumen diameter (2.1 ± 3.05%) compared with bare CoCr stents (9.73 ± 4.93%) and PzF-nanocoated stainless steel stents (9.71 ± 7%; p = 0.04) [27] . Surprisingly, drug-free PzF-nanocoated stents had significantly less late ISR compared with paclitaxel-coated DES (0.3 ± 0.3 mm vs 0.8 ± 0.2 mm in stents coated with an intermediate dose of paclitaxel and 1.5 ± 0.6 mm in high-dose stents; p = 0.04) and showed less inflammation (Kornowski scores of 0.2 ± 0.1 in drug-free stents, 1.7 ± 0.8 in intermediate-dose stents, and 1.3 ± 1.0 in high-dose stents; p = 0.04) [28] .

Optimizing the interface with blood proteins and suggesting enhanced biocompatibility in the absence of anti-proliferative drugs, COBRA PzF was designed to reduce thrombogenicity and to foster endothelialization.

The safety profile of the COBRA PzF stent was investigated in various animal and in vitro studies (Table 2) . Experiments in the porcine coronary artery model showed that compared with BMS, the COBRA PzF stent exhibited significantly larger lumen areas, lower neointimal thickness, and %stenosis, both at 28 days and at 90-days follow-up [29] . Furthermore, inflammation was reduced with COBRA PzF devices. These findings were corroborated by reduced monocyte adhesion and thrombus formation compared with BMS in ex vivo swine carotid-jugular arterio-venous shunt models ( Figure 2 ) [29] . future science group www.futuremedicine.com 

Bioabsorbable polymer-EES Reproduced with permission from [30] .

While the same study demonstrated a similar endothelial coverage over luminal surfaces in the COBRA PzF stent and BMS [29] , our group recently demonstrated enhanced endothelial coverage with COBRA PzF stents compared with contemporary conventional DES in the rabbit iliac artery model [30] . At 14 days, the COBRA PzF stent showed significantly greater endothelial strut coverage compared with bioabsorbable polymer DES and compared with durable polymer DES (99.0% vs 29.6% vs 17.7%; p < 0.001), as assessed by scanning electron microscopy imaging (Figure 3 ) [30] . Furthermore, endothelial barrier protein expression, assessed by immunofluorescent staining for the p120/vascular endothelial cadherin complex, was significantly higher in the COBRA PzF stent compared with bioabsorbable polymer and durable polymer DES (82.6% vs 14.4% vs 12.8%; p ≤ 0.001). Likewise, Evans blue uptake, a marker of leaky endothelium/incomplete endothelial barrier function, was least in COBRA PzF stent when compared with durable polymer and bioabsorbable polymer DES (22.0% vs 70.0% vs 66.4%; p = 0.03).

Durable polymer EES Bioabsorbable polymer EES Reproduced with permission from [30] .

We also evaluated the acute inflammatory potential of the COBRA PzF stent in comparison with contemporary DES in a porcine arteriovenous shunt model by immunofluorescent staining against a neutrophil marker (PM-1) and a monocyte marker (CD14). Inflammatory cell adhesion was similar between COBRA PzF stents and durable polymer DES, but significantly lower in COBRA PzF stents compared with bioabsorbable polymer DES [30] . A recent study evaluated the time course of re-endothelialization with the COBRA PzF stent and reported nearly complete coverage of the stented area at 7 days after stent implantation (99.54 ± 0.25%) in the rabbit iliac artery model, which is the fastest re-endothelialization ever reported in the literature of coronary stents [31] .

Clinical studies with the COBRA PzF device Assessment of The Latest Non-Thrombogenic Angioplasty Stent Trial (ATLANTA) and ATLANTA 2 were first-inman single-arm studies investigating safety and efficacy of a PzF-nanocoated stent, using the Catania™ stent system (CeloNova BioSciences), a predecessor of the COBRA PzF stent [32] . Clinically driven target lesion revascularization at 12 months was 3.6% (two of 55 patients with symptomatic ischemic heart disease), with no deaths, strokes or myocardial infarctions in ATLANTA [32] . Target lesion revascularization rate at 12 months was 6.5% and no late stent thrombosis was recorded up to 12 months, even though dual antiplatelet therapy (DAPT) was prescribed for only 1 month post procedure (unless patients had a myocardial infarction) in the 300 patients recruited for ATLANTA 2 [33] . Adding to these promising results, a substudy in 15 patients from ATLANTA reported 99.5% covered struts, assessed by optical coherence tomography, at 6 months follow-up [34] .

The first clinical study reporting procedural and 1-year clinical outcomes following COBRA PzF coronary stent implantation enrolled 100 real-world patients (71% men, mean age 71.4 ± 11.0 years), 38% of whom had acute coronary syndromes and 26% of whom had multivessel disease (Table 3 ) [35] . Target vessel failure rate as a composite of all-cause mortality, myocardial infarction or target vessel revascularization was 12%, including 2% mortality, 5% periprocedural myocardial infarction (according to the definition proposed by the Academic Research Consortium [36] ), and 5% target lesion revascularization. These rates compared favorably to those seen with other commercially available BMS in the USA [37] [38] [39] . Of note, there were no cases of definite stent thrombosis.

Likewise, the multicenter, prospective, single-arm, nonrandomized PzF Shield (COBRA PzF Stent in Native Coronary Arteries for Early Healing, Thrombus Inihibition, Endothelialization and Avoiding Long-Term Dual Anti-Platelet Therapy) trial, performed in the USA and Europe with 296 patients (70% men, mean age 66 ± 10 years) reported target vessel failure rates (defined as a composite of cardiac death, myocardial infarction, or clinically driven target vessel revascularization) of 11.5% at 9 months, and a mean late lumen loss of 0.84 ± 0.48 mm [40] . In addition, clinically driven TLR was 4.6% and no case of stent thrombosis was reported.

future science group www.futuremedicine.com Considering the antithrombotic properties of the COBRA PzF stent reported from preclinical studies with enhanced endothelialization and low adhesion of platelets and inflammatory cells, and in light of only two subacute stent thrombosis events and no late stent thrombosis among 650 patients receiving either the Catania or COBRA PzF stent [32, 33, 35, 40] , the COBRA PzF stent has been suggested specifically for the treatment of patients with high bleeding risk.

Following stent implantation, DAPT, consisting of aspirin in combination with an ADP receptor P2Y12 inhibitor, is required until endothelialization of the inner stent surface is complete to mitigate against stent thrombosis and ischemic events. While endothelialization of BMS in humans is complete at 1 month after implantation, DES are not fully covered with endothelial cells until 6-12 months [1] . Thus, following PCI for stable coronary artery disease, a minimum duration of DAPT of 1 month is recommended for patients treated with BMS, whereas the default guideline recommendation for DAPT duration after DES implantation is 6-12 months [43, 44] . For many years, patients who could not receive DAPT for more than 1 month because of active bleeding, nonadherence to medical therapy, or planned surgery, have preferably been treated with BMS. However, second-generation DES have proved to be safer than BMS even with respect to ST [45] , and recent studies suggest shorter durations (as little as 1 month) of DAPT for newer-generation DES [46] [47] [48] .

Recently, the multicenter prospective e-COBRA study evaluated safety and efficacy of the COBRA PzF stent in routine clinical practice in patients deemed appropriate for shorter duration of DAPT [41] . The primary end point was MACE (cardiac death, myocardial infarction and target lesion revascularization) at 12 months, the secondary end point was definite stent thrombosis at 12 months. Among 940 patients (72% men, mean age 72.8 ± 13.4 years), 62.5% of whom were considered to have a high bleeding risk and 47% had high ischemic risk (21% STEMI and 26% NSTEMI). DAPT duration was at the principal investigator's discretion. A total of 6% of patients were on single antiplatelet therapy post PCI. A total of 25 and 70% of patients on oral anticoagulant therapy (OAC) stopped DAPT by 1 and 3 months, respectively. Among those without OAC, 16 and 43% stopped DAPT by 1 and 3 months, respectively. MACE occurred in 9.0% of patients, and definite stent thrombosis was reported in 0.7%, suggesting COBRA PzF may be an alternative when short DAPT or even mono antiplatelet therapy is needed.

A recent prospective, consecutive, observational study investigated the safety of single antiplatelet therapy following COBRA PzF implantation in 77 patients (58.5% men, mean age 78.7 ± 8.89 years) at high bleeding risk [42] . A total of 38 patients (49.3%) were discharged with a combination of clopidogrel and OAC (i.e., coumadin or nonvitamin K oral antagonist [novel oral anticoagulant [NOAC] ]), while the other 39 patients (50.7%) were discharged with clopidogrel alone. No patient reached the primary end point of definite stent thrombosis at 1 month (stent thrombosis rate 0.0%). In addition, MACE at 12 months (cardiac death, myocardial infarction and target lesion revascularization) was reported in 3.8%, and no severe bleeding events, strokes, or late stent thromboses were noted. These results compared favorably to those reported with other current devices in older populations [49] or patients with high bleeding risk [47] .

Recently, preliminary results of the COBRA-REDUCE trial (Randomized Trial of COBRA PzF Stenting to REDUCE Duration of Triple Therapy; Clinical Trial Registration NCT02594501) were presented at TCT Connect (17 October 2020) . This multicenter, prospective, randomized, parallel-group, open-label, assessor-blinded clinical trial, conducted at 59 sites in the USA and Europe, was designed to investigate whether coronary stenting with the COBRA PzF stent followed by 14 days of clopidogrel reduced bleeding without increasing thrombo-embolic events compared with FDA-approved DES followed by 3 or 6 months of clopidogrel in patients taking OAC and aspirin [50] .

From a total of 996 patients enrolled (73% male, mean age 75 years), 495 patients were randomized to the COBRA stent group, and 501 patients to DES. 36% of patients were diabetics. All patients had at least one, and 42% had at least two major criteria of high bleeding risk as defined by the Academic Research Consortium for High Bleeding Risk [51] . Preliminary data on 483 patients in the COBRA stent group and 484 patients in the DES control group at 6 months follow-up showed the primary end point, bleeding complications (BARC class ≥2) beyond 14 days until 6 months postrandomization, occurred at 7.5% in the COBRA stent group and 8.9% in the DES group without reaching statistical significance (p = 0.48). While DAPT duration was mandated in the study, novel oral anticoagulant (NOAC) dosing was at the PI's discretion. Subsequently, significantly more patients in the DES/3-6 months DAPT group received a reduced dose of NOAC while on DAPT (56 vs 46%; p = 0.006). This may have contributed to less bleeding in the DES group. The investigators noted that further exploration and analysis to assess the impact of antithrombotic therapy duration, dosing, and the role of aspirin are underway and will be reported in the final results. Nevertheless, when comparing all bleeding events (BARC 1-5) after randomization, fewer events were observed in the COBRA stent group than in the DES group (13.0 vs 18.3%, p = 0.026).

The co-primary end point, a composite of death, myocardial infarction, stroke and stent thrombosis at 6 months was reported in 7.7% of patients treated with COBRA PzF stents and 14 days of DAPT, compared with 5.2% in the standard DES/3-6 months DAPT group. According to these preliminary data, the COBRA PzF stent did not meet the criteria for noninferiority (p for noninferiority = 0.061). However, aside from seven patients who withdrew consent and seven patients who were lost to follow-up, the 6 months follow-up was still incomplete for 15 patients (nine patients in the COBRA PzF group and six patients in the DES group). Since the p-value was only very narrowly missed, the results of these patients might potentially turn the scales, and the final study results are still to be awaited [52] . In addition, 20% of lesions treated with the COBRA PzF stent were at bifurcations, while it was 15% in the DES control group (p = 0.034). Bifurcation lesion intervention is associated with a higher complication rate compared with nonbifurcation lesions [53] , which might have impacted the study results. Indeed, ischemia-driven target lesion revascularization at 6 months follow-up was more frequent in the COBRA PzF group compared with the standard DES control group (3.7 vs 0.9%, p = 0.04).

The final results of COBRA-REDUCE will reveal if in patients on oral anticoagulation 14 days DAPT following implantation of the COBRA PzF stent is non-inferior to 3-6 months DAPT treatment in patients receiving a standard DES. Nevertheless, preliminary data suggest 14 days DAPT following implantation of the COBRA PzF stent is safe, particularly with respect to stent thrombosis which was reported in only 0.6% of patients, corroborating the results of previous clinical studies [35, 40, 42] . Of note, for both groups the preliminary results of COBRA-REDUCE compare favorably with other trials conducted in patients at high bleeding risk, such as LEADERS FREE [16] and Onyx One [54] where DAPT duration was prescribed for 30 days post PCI. The awaited 1-year results of COBRA-REDUCE will shed light on this and clarify particularly in the DES group if 3 months of DAPT should be applied instead of 30 days for this high bleeding risk population.

The duration of DAPT following stent implantation is subject of ongoing debate. The COBRA PzF nanocoated coronary stent has been associated with accelerated endothelialization relative to drug-eluting stents, reduced future science group www.futuremedicine.com inflammation, and thromboresistance in preclinical studies, suggesting more flexible DAPT requirements with potential benefits especially in patients at high bleeding risk. Although the safety of shorter duration of DAPT (i.e., 2 weeks) after COBRA PzF stent implantation has been proven, preliminary results of COBRA-REDUCE do not show a significant reduction of bleeding complications (BARC ≥2) in a high bleeding risk cohort. The p-value for noninferiority to DES/3-6 months DAPT treatment regarding the composite of death, MI, stent thrombosis (definite/probable) and ischemic stroke in this high-risk population was missed very narrowly, yet the final results of the trial are to be awaited.

More confirmative studies are needed to determine whether single anti-platelet therapies in subjects at high bleeding risk receiving COBRA PzF are safe. In addition, the minimum duration of DAPT after COBRA PzF stenting appears to be another area in which further data could help to determine its suitability for such patients.

• The unique design of the COBRA PzF stent has been associated with enhanced endothelialization and reduced thromboembolic complications in several clinical and preclinical studies. Antithrombotic strategies with COBRA PzF • Short-term dual antiplatelet therapy (DAPT) following implantation of the COBRA PzF device has shown to be safe. This is especially important in cases where early termination of DAPT is indispensable. Relevance of COBRA PzF for patients with high bleeding risk • In cases with high bleeding risk, the COBRA PzF stent should be considered as an alternative for bare metal stent which have been associated with higher restenosis rates and worse outcome. Future perspective • Final results of COBRA-REDUCE will reveal if treatment with the COBRA PzF stent, followed by 2 weeks of DAPT, is non-inferior to standard drug-eluting stents implantation and 3-6 months of DAPT in a high bleeding risk collective.

Open access 

received institutional research support from NIH-HL141425, Leducq Foundation Grant, 4C Medical, 4Tech, Abbott Vascular, Ablative Solutions, Absorption Systems, Advanced NanoTherapies

Innovalve, Innovative, Cardiovascular Solutions, Intact Vascular

Abbott Vascular; Boston Scientific; Celonova; Cook Medical

Virmani has received honoraria from Abbott Vascular

Boston Scientific; Cook Medical; Cordis; CSI; Lutonix Bard; Medtronic

Gore; Spectranetics; and is a consultant to Abbott Vascular; Boston Scientific; Celonova; Cook Medical; CSI; Edwards Lifescience; Lutonix Bard

Terumo Corporation

Barakat is an employee of CeloNova BioSciences. The authors have no

Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk

• Shows for the first time a delayed healing in drug-eluting stents (DES) in humans

Is there light at the end of the thin-strut tunnel?: in vitro insights on strut thickness impact on thrombogenicity in bioresorbable stents or scaffolds

Intracoronary stenting and angiographic results: strut thickness effect on restenosis outcome (ISAR-STEREO) trial

Intracoronary stenting and angiographic results: strut thickness effect on restenosis outcome (ISAR-STEREO-2) trial

Thrombogenicity and early vascular healing response in metallic biodegradable polymer-based and fully bioabsorbable drug-eluting stents

Acute thrombogenicity of a durable polymer everolimus-eluting stent relative to contemporary drug-eluting stents with biodegradable polymer coatings assessed ex vivo in a swine shunt model

Impact of stent thickness on clinical outcomes in small vessel and bifurcation lesions: a RAIN-CARDIOGROUP VII sub-study

Pathology of second-generation everolimus-eluting stents versus first-generation sirolimus-and paclitaxel-eluting stents in humans

Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-eluting stent: should we be cautious?

Delayed arterial healing and increased late stent thrombosis at culprit sites after drug-eluting stent placement for acute myocardial infarction patients: an autopsy study

Long-term effects of polymer-based, slow-release, sirolimus-eluting stents in a porcine coronary model

Stent thrombogenicity early in high-risk interventional settings is driven by stent design and deployment and protected by polymer-drug coatings

Endothelial cell recovery, acute thrombogenicity, and monocyte adhesion and activation on fluorinated copolymer and phosphorylcholine polymer stent coatings

Very late pathological responses to cobalt-chromium everolimus-eluting, stainless steel sirolimus-eluting, and cobalt-chromium bare metal stents in humans

Polymer-free sirolimus-and probucol-eluting versus new generation zotarolimus-eluting stents in coronary artery disease: the intracoronary stenting and angiographic results: test efficacy of sirolimus-and probucol-eluting versus zotarolimus-eluting stents (ISAR-TEST 5) trial

Improved safety and reduction in stent thrombosis associated with biodegradable polymer-based biolimus-eluting stents versus durable polymer-based sirolimus-eluting stents in patients with coronary artery disease: final 5-year report of the LEADERS (Limus Eluted From A Durable Versus ERodable Stent Coating) randomized, noninferiority trial

10-year outcomes from a randomized trial of polymer-free versus durable polymer drug-eluting coronary stents

Final 3-year outcomes of mistent biodegradable polymer crystalline sirolimus-eluting stent versus xience permanent polymer everolimus-eluting stent: insights from the DESSOLVE III all-comers randomized trial

Long-term outcomes of biodegradable versus second-generation durable polymer drug-eluting stent implantations for myocardial infarction

Biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents in patients with ST-segment elevation myocardial infarction (BIOSTEMI): a single-blind, prospective, randomised superiority trial

Abluminal biodegradable polymer biolimus-eluting versus durable polymer everolimus-eluting stent in patients with diabetes mellitus: 5 years follow-up from the COMPARE II trial

Five-year outcome of a randomised trial comparing second-generation drug-eluting stents using either biodegradable polymer or durable polymer: the NOBORI biolimus-eluting versus XIENCE/PROMUS everolimus-eluting stent trial (NEXT)

Meta-analysis of randomized clinical trials comparing biodegradable polymer drug-eluting stent to second-generation durable polymer drug-eluting stents

Investigation of the thermostability of poly

Plasma protein adsorption and platelet adhesion on poly

• Presents pilot experiments on PzF-coated vascular stents, showing improved thromboresistance and reduced late in-stent restenosis compared to bare metal stent (BMS) in a rabbit model

Reduction of late in-stent stenosis in a porcine coronary artery model by cobalt chromium stents with a nanocoat of polyphosphazene (Polyzene-F)

Paclitaxel-induced arterial wall toxicity and inflammation: part 2 -long-term tissue response in a minipig model

Preclinical evaluation of a novel polyphosphazene surface modified stent

Preclinical study showing evidence of reduced restenosis, inflammation and thrombus formation in COBRA PzF as compared to BMS using a porcine coronary artery model, human monocyte assays and a porcine ex vivo shunt model

Thromboresistance and functional healing in the COBRA PzF stent versus competitor DES: implications for dual antiplatelet therapy

Preclinical study showing enhanced endothelialization of COBRA PzF compared with bioabsorbable and durable polymer DES in a rabbit iliac artery model, as well as a comparable inflammatory cell adhesion between COBRA PzF and durable polymer DES but lower inflammatory cell adhesion in COBRA PzF compared to the bioabsorbable polymer DES in a porcine shunt model

Time course of reendothelialization with polyzene-F nanocoated cobra PzF™ coronary stent on rabbit iliac arteries

This preclinical study shows a nearly complete coverage of COBRA PzF at as early as 7 days after stent implantation in a rabbit iliac artery model

First-in-man 1-year clinical outcomes of the Catania Coronary Stent System with Nanothin Polyzene-F in de novo native coronary artery lesions: the ATLANTA (Assessment of The LAtest Non-Thrombogenic Angioplasty stent) trial

• First in man single-arm study showing safety and efficacy of a PzF-nanocoated stent with target lesion revascularization occurring in 3.6% at 12 months

Safety and effectiveness of the Catania Polyzene-F coated stent in real world clinical practice: 12-month results from the ATLANTA 2 registry

Optical coherence tomographic results at six-month follow-up evaluation of the CATANIA coronary stent system with nanothin Polyzene-F surface modification (from the Assessment of The LAtest Non-Thrombogenic Angioplasty Stent [ATLANTA] trial)

Immediate and 1-year follow-up with the novel nanosurface modified COBRA PzF stent

This is the first clinicial study investigating COBRA PzF, showing favorable rates of target vessel failure in COBRA PzF compared to other commercially available BMS in the USA

Overview of the 2006 Food and Drug Administration Circulatory System Devices Panel meeting on drug-eluting stent thrombosis

Randomized, double-blind, multicenter study of the Endeavor zotarolimus-eluting phosphorylcholine-encapsulated stent for treatment of native coronary artery lesions: clinical and angiographic results of the ENDEAVOR II trial

Cobalt-chrome MULTI-LINK VISION-stent implantation in diabetics and complex lesions: results from the DaVinci-Registry

Primary endpoint results of the OMEGA Study: one-year clinical outcomes after implantation of a novel platinum chromium bare metal stent

9-Month clinical and angiographic outcomes of the COBRA Polyzene-F NanoCoated coronary stent system

This clinical study presents the results of the PzF Shield Trial, reporting target vessel failure rates of 11

Evaluation of the safety and efficacy of the Cobra PzF NanoCoated coronary stent in routine, consecutive, prospective, and high-risk patients: the e-Cobra study

Clinical study in 940 patients reporting a satisfactory major adverse cardiac event rate of 9.0% and stent thrombosis rate of 0.7% at 12months after implantation of COBRA PzF despite shorter duration of dual antiplatelet therapy or mono antiplatelet therapy in most patients

MAPT (mono antiplatelet therapy) as regular regimen after COBRA PzF™ NanoCoated Coronary Stent (NCS) implantation

Investigates the safety of single antiplatelet therapy after COBRA PzF implantation in patients at high bleeding risk and reported no case of stent thrombosis occurred at 1 month. In addition, major adverse cardiac events occurred in 3

ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS)

ACC/AHA Guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines

Stent thrombosis with drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis

Zotarolimus-eluting versus bare-metal stents in uncertain drug-eluting stent candidates

Polymer-free drug-coated coronary stents in patients at high bleeding risk

One-year outcome of a prospective trial stopping dual antiplatelet therapy at 3 months after everolimus-eluting cobalt-chromium stent implantation: shortT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent (STOPDAPT) trial

Drug-eluting stents in elderly patients with coronary artery disease (SENIOR): a randomised single-blind trial

Design and rationale of a randomized trial of COBRA PzF stenting to REDUCE duration of triple therapy (COBRA-REDUCE)

Defining high bleeding risk in patients undergoing percutaneous coronary intervention: a consensus document from the Academic Research Consortium for High Bleeding Risk

COBRA PzF Stenting to REDUCE Duration of Triple Therapy -COBRA-RDUCE

Histopathologic and physiologic effect of bifurcation stenting: current status and future prospects

Polymer-based or polymer-free stents in patients at high bleeding risk

other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.