Interleukin-10 -1082 G/A polymorphism and its association with early or severe presentation of coronary artery disease: A systematic review and meta-analysis.

INTRODUCTION: Interleukin-10 (IL-10) is an anti-inflammatory cytokine with potent deactivating properties on macrophages and T cells; and plays an important role in atherosclerotic plaque maturation and rupture. A guanine (G) to adenine (A) substitution in the IL-10 gene at -1082 bp (rs1800896) has been associated with reduced in IL-10 production in vitro. Against this background, we tested the association of IL-10 -1082G/A with early or severe presentation of coronary artery disease (CAD) using a systematic review and updated meta-analysis of published association studies. MATERIALS AND METHODS: Relevant studies were identified following a comprehensive online search on PubMed, EMBASE, MEDLINE, Scopus, Cochrane library and Web of Science databases and stratified into two subgroups based on mode of CAD presentation: early or severe and non-severe. Study level odds ratios (ORs) and their 95% confidence intervals (CI) were pooled using random effects employing a Z test. RESULTS: A total of 24 studies were included for quantitative synthesis with a cumulative sample of 19,135 (11,143 cases / 7,992 controls). A significant association was derived for IL-10 -1082G/A and early or severe CAD via dominant, recessive, and allelic genetic model comparisons [OR 1.24 (95 % CI 1.02, 1.50), p = 0.03; OR 1.32 (95 % CI 1.03, 1.69), p = 0.03 and OR 1.18 (95 % CI 1.02, 1.36), p = 0.02 respectively]. In contrast, no significant association was seen for the pooled group or non-severe CAD subgroup (p = NS). Sensitivity analysis showed consistent results. CONCLUSIONS: IL-10 -1082G/A appears to be associated with early or severe presentation of CAD. Further studies are warranted to confirm this association.

Glu298Asp variant of the endothelial nitric oxide synthase gene and acute coronary syndrome or premature coronary artery disease: A systematic review and meta-analysis.

INTRODUCTION: Several published studies have reported an association between the Glu298Asp polymorphism (rs1799983), residing in the endothelial nitric oxide synthase (NOS3) gene, and lower levels of circulating nitric oxide, as well as an increased risk of coronary artery disease (CAD). However, association status of this genetic variant with acute coronary syndrome (ACS) or premature CAD (PCAD) is still unclear. Against this background, we conducted a systematic review and study level meta-analysis to assess the association of the NOS3 Glu298Asp polymorphism with ACS or PCAD. MATERIALS AND METHODS: A comprehensive online search to identify relevant studies was performed on several databases including PubMed, EMBASE, MEDLINE, Scopus, Cochrane library and Web of Science. The identified studies were stratified into two ancestral subgroups: 'European ancestry' and 'All other ancestries combined'. Study level odds ratios (ORs) and their 95% confidence intervals (CI) were pooled using random/fixed effects employing a Z test. RESULTS: Out of a total of 195 distinct records identified through online search, 37 articles with 39 different studies, with a total sample size of 27,441 (11,516 cases/15,925 controls) were included for quantitative synthesis. Pooled results suggested significant associations of the NOS3 Glu298Asp polymorphism with ACS or PCAD through dominant as well as allelic genetic models (p ≤ 0.002), primarily driven by the 'All other ancestries combined' subgroup. The 'All other ancestries combined' subgroup demonstrated an additional risk of 36% for ACS or PCAD, through both dominant and allelic genetic models (OR = 1.36, 95%CI = 1.13, 1.63, p = 0.001 and OR = 1.36, 95%CI = 1.14, 1.61, p = 0.0005 respectively). On the other hand, the 'European ancestry' subgroup did not show any significant associations. Sensitivity analysis and a sub-analysis for the myocardial infarction endpoint further supported these observed associations. CONCLUSIONS: This meta-analysis indicates towards an association between the NOS3 Glu298Asp polymorphism and ACS or PCAD, predominantly driven by 'All other ancestries combined' subgroup. In contrast, the 'European ancestry' subgroup did not demonstrate any significant association. Further large-scale investigations are required to confirm our derived results.

A prospective trial of a novel low-dose paclitaxel-coated balloon therapy in patients with restenosis in drug-eluting coronary stents Intracoronary Stenting and Angiographic Results: Optimizing Treatment of Drug Eluting Stent In-stent REstenosis 3A (ISAR-DESIRE 3A).

OBJECTIVES: We investigated the clinical efficacy of a paclitaxel-coated balloon (PCB) with a novel matrix coating and reduced drug concentration in comparison with a widely used PCB with iopromide excipient. METHODS: We prospectively enrolled patients with restenosis in drug-eluting stents. All patients were treated with a novel low-dose PCB with citrate-based excipient (Agent PCB). Angiographic follow-up was scheduled at 6-8 months. Outcomes were compared against those of patients treated with iopromide excipient PCB (SeQuent Please PCB) enrolled in a trial with identical inclusion and exclusion criteria. The primary endpoint was percent diameter stenosis (%DS) at follow-up angiography. The primary hypothesis was that the investigational device would be non-inferior to the control device (ClinicalTrials.gov Identifier: NCT02367495). RESULTS: One hundred twenty-five patients with 151 lesions were enrolled. Mean age was 68.1 ± 10.2 years, 40.8% had diabetes mellitus and 80.1% had focal morphology in-stent restenosis. Follow-up angiography data at 6-8 months was available for 102 (81.6%) patients. The Agent PCB was non-inferior to the SeQuent Please PCB in terms of the primary endpoint (38.9 ± 17.5 vs. 38.1 ± 21.5%; p non-inferiority  = 0.0056). Late lumen loss was also comparable between the groups (0.35 ± 0.55 vs. 0.37 ± 0.59; p = 0.71). There was no difference between the groups in the incidence of TLR (27.7% vs. 22.1%; p = 0.31), death or myocardial infarction (4.2% vs. 4.4%; p = 0.92) or target lesion thrombosis (1.0% vs. 0.7%; p = 0.93). CONCLUSION: In patients with DES restenosis, angioplasty with a novel PCB with citrate-based excipient was non-inferior to PCB with iopromide excipient in terms of angiographic outcome.

Angiographic performance of everolimus-eluting stents for the treatment of coronary in-stent restenosis in daily practice.

OBJECTIVES: The present study aims to analyze the angiographic anti-restenotic performance of durable polymer everolimus-eluting stents (EES) for the treatment of in-stent restenosis (ISR) in daily practice. BACKGROUND: Randomized data is available supporting the use of drug-coated balloons and drug-eluting stents for the treatment of ISR; however, additional real-world data including angiographic follow-up is needed. METHODS: Patients who underwent EES-implantation for the treatment of drug-eluting stent ISR and attended for a 6-8 months angiographic surveillance were analyzed. Off-line assessment of the angiograms was conducted at a central quantitative coronary angiographic core laboratory. RESULTS: A total of 426 patients with ISR were treated with EES and had undergone angiographic follow-up. The mean age was 66.8 ± 9.9 years and 27.5% suffered from diabetes. A total of 459 lesions were treated. The diameter stenosis decreased from 64.3 ± 19.1% (preprocedural) to 12.0 ± 6.4% (postprocedural). At 6-8 months angiographic follow-up, the in-segment diameter stenosis was 38.3 ± 21.7% and the in-stent late luminal loss was 0.54 ± 0.74 mm in the treated area analysis. The rate of recurrent binary restenosis was 25.7%. CONCLUSIONS: In the setting of ISR, the angiographic anti-restenotic efficacy of stenting with EES is comparable to that observed in randomized clinical trials and less favorable than its performance in patients undergoing stenting for de novo disease.

Association of interleukin 6 -174 G/C polymorphism with coronary artery disease and circulating IL-6 levels: a systematic review and meta-analysis.

INTRODUCTION: Circulating IL-6 levels and at least one polymorphic form of IL6 gene (IL6 -174 G/C, rs1800795) have been shown to be independently associated with coronary artery disease (CAD) by several investigators. Despite more than 12 published meta-analyses on this subject, association of -174 G/C with CAD, especially amongst distinct ancestral population groups remain unclear. We, therefore, conducted a systematic review and an updated meta-analysis to comprehensively ascertain the association of IL6 -174 G/C with CAD and circulating IL-6 levels. MATERIALS AND METHODS: Relevant case-control/cohort studies investigating association of -174 G/C with CAD and circulating IL-6 levels were identified following a comprehensive online search. Association status for CAD was determined for the pooled sample, as well as separately for major ancestral subgroups. Association status for circulating IL-6 levels was assessed for the pooled sample, as well as separately for CAD cases and CAD free controls. Study-level odds ratios (OR) and 95% confidence intervals (CI) were pooled using random/fixed-effects model. RESULTS: Quantitative synthesis for the CAD endpoint was performed using 55 separate qualifying studies with a collective sample size of 51,213 (19,160 cases/32,053 controls). Pooled association of -174 G/C with CAD was found to be statistically significant through dominant (OR 1.15; 95% CI 1.05-1.25, p = 0.002) as well as allelic genetic model comparisons (OR 1.13, 95% CI 1.06-1.21, p = 0.0003). This effect was largely driven by Asian and Asian Indian ancestral subgroups, which also showed significant association with CAD in both genetic model comparisons (OR range 1.29-1.53, p value range ≤ 0.02). Other ancestral subgroups failed to show any meaningful association. Circulating IL-6 levels were found to be significantly higher amongst the 'C' allele carriers in the pooled sample (Standard mean difference, SMD 0.11, 95% CI 0.01-0.22 pg/ml, p = 0.009) as well as in the CAD free control subgroup (SMD 0.10, 95% CI 0.02-0.17 pg/ml, p = 0.009), though not in the CAD case subgroup (SMD 0.17, 95% CI = - 0.02 to 0.37, p = 0.12). CONCLUSIONS: The present systematic review and meta-analysis demonstrate an overall association between IL6 -174 G/C polymorphism and CAD, which seems to be mainly driven by Asian and Asian Indian ancestral subgroups. Upregulation of plasma IL-6 levels in the 'C' allele carriers seems to be at least partly responsible for this observed association. This warrants further investigations with large, structured case-control studies especially amongst Asian and Asian Indian ancestral groups.

Defining High Bleeding Risk in Patients Undergoing Percutaneous Coronary Intervention.

Identification and management of patients at high bleeding risk undergoing percutaneous coronary intervention are of major importance, but a lack of standardization in defining this population limits trial design, data interpretation, and clinical decision-making. The Academic Research Consortium for High Bleeding Risk (ARC-HBR) is a collaboration among leading research organizations, regulatory authorities, and physician-scientists from the United States, Asia, and Europe focusing on percutaneous coronary intervention-related bleeding. Two meetings of the 31-member consortium were held in Washington, DC, in April 2018 and in Paris, France, in October 2018. These meetings were organized by the Cardiovascular European Research Center on behalf of the ARC-HBR group and included representatives of the US Food and Drug Administration and the Japanese Pharmaceuticals and Medical Devices Agency, as well as observers from the pharmaceutical and medical device industries. A consensus definition of patients at high bleeding risk was developed that was based on review of the available evidence. The definition is intended to provide consistency in defining this population for clinical trials and to complement clinical decision-making and regulatory review. The proposed ARC-HBR consensus document represents the first pragmatic approach to a consistent definition of high bleeding risk in clinical trials evaluating the safety and effectiveness of devices and drug regimens for patients undergoing percutaneous coronary intervention.

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

Identification and management of patients at high bleeding risk undergoing percutaneous coronary intervention are of major importance, but a lack of standardization in defining this population limits trial design, data interpretation, and clinical decision-making. The Academic Research Consortium for High Bleeding Risk (ARC-HBR) is a collaboration among leading research organizations, regulatory authorities, and physician-scientists from the United States, Asia, and Europe focusing on percutaneous coronary intervention-related bleeding. Two meetings of the 31-member consortium were held in Washington, DC, in April 2018 and in Paris, France, in October 2018. These meetings were organized by the Cardiovascular European Research Center on behalf of the ARC-HBR group and included representatives of the US Food and Drug Administration and the Japanese Pharmaceuticals and Medical Devices Agency, as well as observers from the pharmaceutical and medical device industries. A consensus definition of patients at high bleeding risk was developed that was based on review of the available evidence. The definition is intended to provide consistency in defining this population for clinical trials and to complement clinical decision-making and regulatory review. The proposed ARC-HBR consensus document represents the first pragmatic approach to a consistent definition of high bleeding risk in clinical trials evaluating the safety and effectiveness of devices and drug regimens for patients undergoing percutaneous coronary intervention.

Comparative prognostic value of postprocedural creatine kinase myocardial band and high-sensitivity troponin T in patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention.

OBJECTIVES: We aimed to assess the prognostic value of postprocedural creatine kinase myocardial band (CK-MB) and cardiac troponin (cTn) in patients with non-ST-segment elevation myocardial infarction (NSTEMI). BACKGROUND: Whether postprocedural CK-MB or cTn is a better biomarker to stratify the risk after percutaneous coronary intervention (PCI) remains unknown. METHODS: This study included 2,077 patients with NSTEMI undergoing early PCI. Peak postprocedural values of CK-MB and high-sensitivity cTn T (hs-cTnT) were analyzed. The primary outcome was 3-year mortality. RESULTS: The median values of peak postprocedural CK-MB and hs-cTnT were 18.3 U L-1 and 0.140 µg L-1 , respectively. Overall, 211 patients died during follow-up. There were 129 deaths in patients with CK-MB >the median value and 82 deaths in those with CK-MB ≤the median value (Kaplan-Meier estimates of 3-year mortality, 18.9% and 14.0%, respectively; hazard ratio [HR] = 1.52, 95% confidence interval [CI] 1.16-2.01; P < 0.001). There were 134 deaths in patients with hs-cTnT >the median value and 77 deaths in patients with hs-cTnT ≤the median value (Kaplan-Meier estimates of 3-year mortality, 19.9% and 13.2%, respectively; HR = 1.90 [1.44-2.52]; P < 0.001). After adjustment, peak postprocedural CK-MB (adjusted HR = 1.05 [1.02-1.07], P < 0.001 for each 24 U L-1 increment) and hs-cTnT (adjusted HR = 1.12 [1.01-1.25], P = 0.037 for each unit higher log hs-cTnT) remained independently associated with the risk of 3-year mortality. The C-statistic(s) of the model with CK-MB and hs-cTnT were 0.789 [0.757-0.817] and 0.793 [0.762-0.821], respectively (P = 0.585). CONCLUSION: In patients with NSTEMI undergoing early PCI, peak postprocedural CK-MB and hs-cTnT are independently associated with the risk of 3-year mortality. © 2017 Wiley Periodicals, Inc.

Current Use of Intracoronary Imaging in Interventional Practice　- Results of a European Association of Percutaneous Cardiovascular Interventions (EAPCI) and Japanese Association of Cardiovascular Interventions and Therapeutics (CVIT) Clinical Practice Survey.

BACKGROUND: This study evaluated the views of the cardiology community on the clinical use of coronary intravascular imaging (IVI).Methods and Results:A web-based survey was distributed to 31,893 individuals, with 1,105 responses received (3.5% response rate); 1,010 of 1,097 respondents (92.1%) self-reported as interventional cardiologists, 754 (68.7%) with >10 years experience. Overall, 96.1% had personal experience with IVI (95.5% with intravascular ultrasound [IVUS], 69.8% with optical coherence tomography [OCT], and 7.9% with near-infrared spectroscopy); 34.7% of respondents were from Europe and 52.0% were from Asia (45.4% from Japan). The most commonly reported indications for IVI were optimization of stenting (88.5%), procedural/strategy guidance (79.6%), and guidance of left main interventions (77.0%). Most respondents reported perceived equipoise regarding choice between IVUS and OCT for guidance of coronary intervention. High cost (65.9%) and prolongation of the procedure (35.0%) were the most commonly reported factors limiting use. IVI was used more frequently (>15% of cases guided by IVI) in Japan than Europe (96.6% vs. 10.4%, respectively; P<0.001) and by operators with longer interventional experience. CONCLUSIONS: In a sample of predominantly experienced interventional cardiologists, there was a high rate of personal experience with IVI in clinical practice. The most commonly identified indications for IVI were optimization of stenting, procedural/strategy guidance, and guidance of left main interventions. Variability in practice patterns is substantial according to geographic region and interventional experience.

Five-year follow-up of polymer-free sirolimus- and probucol-eluting stents versus new generation zotarolimus-eluting stents in patients presenting with st-elevation myocardial infarction.

BACKGROUND: Patients with ST-segment elevation myocardial infarction (STEMI) undergoing drug-eluting stent (DES) implantation are at increased risk of late adverse events, partly explained by an exaggerated inflammatory reaction to durable-polymer stent coatings. OBJECTIVES: We sought to investigate whether implantation of polymer-free DES would reduce this risk. METHODS: In the ISAR-TEST 5 (the Intracoronary Stenting and Angiographic Results: Test Efficacy of Sirolimus- and Probucol- and Zotarolimus-Eluting Stents) trial, patients were randomly allocated to receive a polymer-free sirolimus- and probucol-eluting stent or a new generation durable-polymer zotarolimus-eluting stent. We analyzed late clinical outcomes in the subgroup of patients presenting with STEMI. The primary endpoint was the combined incidence of cardiac death, target vessel-related myocardial infarction or target lesion revascularization at 5 years. RESULTS: 311 patients with STEMI were randomized to receive sirolimus- and probucol-eluting stents (n = 215) or zotarolimus-eluting stents (n = 96). At 5 years, there was no difference in the incidence of the primary endpoint in patients treated with sirolimus- and probucol-eluting stents versus zotarolimus-eluting stents (18.3% versus 20.1% respectively, hazard ratio = 0.87, 95% CI, 0.50-1.51; P = 0.62). Rates of the individual components of the primary endpoint were also comparable in both groups. The incidence of definite/probable stent thrombosis was 1.4% versus 1.0% respectively (hazard ratio = 1.35, 95% CI, 0.14-12.94, P = 0.80). CONCLUSIONS: Long-term outcomes of patients with STEMI treated with polymer-free sirolimus- and probucol-eluting stents versus durable-polymer zotarolimus-eluting stents were similar. Stent thrombosis rates were low and comparable in both treatment groups, with no events beyond 12 months. CLINICAL TRIAL REGISTRATION: Registered at ClinicalTrials.gov (Identifier NCT 00598533) © 2016 Wiley Periodicals, Inc.

Five-year clinical outcomes in patients with diabetes mellitus treated with polymer-free sirolimus- and probucol-eluting stents versus second-generation zotarolimus-eluting stents: a subgroup analysis of a randomized controlled trial.

BACKGROUND: Improved outcomes in patients with diabetes mellitus undergoing percutaneous coronary intervention remain an unmet clinical need. We assessed the long-term efficacy and safety of novel polymer-free sirolimus- and probucol-eluting stent in diabetic patients enrolled in intracoronary stenting and angiographic results: test efficacy of sirolimus- and probucol-eluting versus zotarolimus-eluting stents 5 trial. METHODS: In a pre-specified subgroup analysis, outcomes of diabetic patients treated with a sirolimus- and probucol-eluting stent or a second-generation zotarolimus-eluting stent were compared. The primary endpoint was a device-oriented composite outcome comprising cardiac death, target vessel-related myocardial infarction (MI), or target lesion revascularization (TLR) at 5-year follow-up. Event-free survival was assessed using the Kaplan-Meier method. Hazard ratios (HR) and 95 % confidence intervals (CI) were estimated from univariate Cox proportional hazards models. RESULTS: A total of 870 patients with diabetes mellitus were treated with either a sirolimus- and probucol-eluting stent (n = 575) or a second-generation zotarolimus-eluting stent (n = 295). At 5 years, the rate of device-oriented composite endpoint was comparable between the sirolimus- and probucol-eluting stent and the second-generation zotarolimus-eluting stent (32.9 versus 33.4 %, HR 0.88, 95 % CI 0.76-1.26). No significant differences were observed between the sirolimus- and probucol-eluting stent and the second-generation zotarolimus-eluting stent groups in the incidence of cardiac death (15.6 versus 16.7 % HR 0.92, 95 % CI 0.63-1.32), target-vessel MI (4.6 versus 6.6 %, HR 0.73, 95 % CI 0.40-1.34), and TLR (18.6 versus 18.8 %, HR 1.00, 95 % CI, 0.72-1.41). The rate of definite or probable stent thrombosis was low and similar in both groups (2.5 versus 2.6 %, HR 1.02, 95 % CI, 0.41-2.52). CONCLUSIONS: In patients with diabetes the long-term efficacy and safety of a polymer-free sirolimus- and probucol-eluting stent were comparable to a second-generation durable polymer zotarolimus-eluting stent. Trial registration ClinicalTrials.gov NCT00598533. Registered 10 January 2008.

Applied coronary physiology for planning and guidance of percutaneous coronary interventions. A clinical consensus statement from the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the European Society of Cardiology.

The clinical value of fractional flow reserve and non-hyperaemic pressure ratios are well established in determining an indication for percutaneous coronary intervention (PCI) in patients with coronary artery disease (CAD). In addition, over the last 5 years we have witnessed a shift towards the use of physiology to enhance procedural planning, assess post-PCI functional results, and guide PCI optimisation. In this regard, clinical studies have reported compelling data supporting the use of longitudinal vessel analysis, obtained with pressure guidewire pullbacks, to better understand how obstructive CAD contributes to myocardial ischaemia, to establish the likelihood of functionally successful PCI, to identify the presence and location of residual flow-limiting stenoses and to predict long-term outcomes. The introduction of new functional coronary angiography tools, which merge angiographic information with fluid dynamic equations to deliver information equivalent to intracoronary pressure measurements, are now available and potentially also applicable to these endeavours. Furthermore, the ability of longitudinal vessel analysis to predict the functional results of stenting has played an integral role in the evolving field of simulated PCI. Nevertheless, it is important to have an awareness of the value and challenges of physiology-guided PCI in specific clinical and anatomical contexts. The main aim of this European Association of Percutaneous Cardiovascular Interventions clinical consensus statement is to offer up-to-date evidence and expert opinion on the use of applied coronary physiology for procedural PCI planning, disease pattern recognition and post-PCI optimisation.

Antithrombotic Therapy With or Without Aspirin After Percutaneous Coronary Intervention or Acute Coronary Syndrome in Patients Taking Oral Anticoagulation: A Meta-Analysis and Network Analysis of Randomized Controlled Trials.

INTRODUCTION: Trials investigating aspirin omission in patients taking oral anticoagulation (OAC) after percutaneous coronary intervention (PCI) or acute coronary syndrome (ACS) were not powered to assess rates of major bleeding or ischemic events. METHODS: We performed an updated meta-analysis and network analysis of randomized trials comparing treatment with or without aspirin in patients taking OAC and a P2Y12-inhibitor after PCI or ACS. The primary outcome was TIMI major bleeding. RESULTS: Five trials enrolling 11,542 patients allocated to antithrombotic regimens omitting (n = 5795) or including aspirin (n = 5747) were included. Aspirin omission was associated with a lower risk of TIMI major bleeding (RR = 0.56, 95% CI [0.44-0.71]; P < 0.001) but a trend towards a higher risk of MI (RR = 1.21, 95% CI [0.99-1.47]; P = 0.06), which was significantly higher when only non-vitamin K antagonist OAC (NOAC)-based trials were considered (Pinteraction = 0.02). The risk of stent thrombosis was comparable with both strategies (RR = 1.29, 95% CI [0.87-1.90]; P = 0.20), with a trend towards a higher risk of ST with aspirin omission when only NOAC-based trials were considered (Pinteraction = 0.06). Risks of stroke and death were similar with both strategies. Network meta-analysis ranked dabigatran (low dose) without aspirin as the best strategy for bleeding reduction (P-score = 0.86) and apixaban with aspirin as the best strategy for MI reduction (P-score = 0.66). CONCLUSIONS: In patients taking OAC after PCI or ACS, aspirin omission is associated with a lower risk of TIMI major bleeding, with a numerically increased risk of MI, which is statistically significant when only NOAC-based trials are considered. This supports individualization of the treatment regimen based on patient risk.

Design and Rationale of a Randomized Trial of COBRA PzF Stenting to REDUCE Duration of Triple Therapy (COBRA-REDUCE).

BACKGROUND/PURPOSE: A coronary stent with thromboresistant and pro-healing properties such as the polymer polyzene F-coated (COBRA PzF) stent might safely allow for a very short duration of triple therapy in patients taking oral anticoagulation (OAC) who undergo coronary stenting. METHODS: The COBRA-REDUCE trial is a prospective, multinational, randomized, open-label, assessor-blinded trial. A total of 996 patients at high bleeding risk because of requirement for OAC (with a vitamin K antagonist or non-vitamin K antagonist for any indication) will be randomized at sites in the United States and Europe to treatment with the COBRA-PzF stent followed by very short duration (14 days) DAPT or a Food and Drug Administration (FDA)-approved new generation drug-eluting stent followed by guideline-recommended DAPT duration (3 or 6 months). Two co-primary endpoints will be tested at 6 months: a bleeding co-primary endpoint (bleeding academic research consortium [BARC] ≥2 bleeding beyond 14 days or after hospital discharge, whichever is later [superiority hypothesis]) and a thrombo-embolic co-primary endpoint (the composite of all-cause death, myocardial infarction, definite/probable stent thrombosis or ischaemic stroke [non-inferiority hypothesis]). The trial is registered at clinicaltrials.gov (NCT02594501). CONCLUSION: The COBRA-REDUCE trial will determine whether coronary stenting with the COBRA PzF stent followed by 14 days of clopidogrel will reduce bleeding without increasing thrombo-embolic events compared with FDA-approved DES followed by 3-6 months clopidogrel in patients taking OAC and aspirin.

Outcomes after complete dissolution of everolimus-eluting bioresorbable scaffolds implanted during routine practice.

INTRODUCTION AND OBJECTIVES: Long-term outcomes of unselected patients treated with bioresorbable vascular scaffold (BVS) implantation are lacking, especially for the period after complete dissolution of the BVS. This study sought to evaluate 5-year outcomes in patients treated with BVS in routine practice. METHODS: Consecutive patients who underwent implantation of everolimus-eluting BVS during routine clinical practice at 2 high-volume centres in Germany were studied. The patients were followed-up for up to 5 years. The primary endpoints of interest were the composite of death, myocardial infarction and target lesion revascularization, as well as definite scaffold thrombosis. RESULTS: A total of 419 patients (mean age 66.6 ± 10.9 years; 31.5% had diabetes) were included, of whom 38.9% presented with an acute coronary syndrome. Of the 527 lesions treated, 49.0% were classified as complex and 13.1% were bifurcation lesions. At 5 years, the composite clinical endpoint occurred in 33.1% of patients and definite scaffold thrombosis occurred in 4.7%. Most definite scaffold thrombosis occurred within 2 years after BVS implantation. CONCLUSIONS: In patients treated with BVS implantation in routine clinical practice the rates of adverse clinical events at 5 years were high, including a considerable incidence of scaffold thrombosis.