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Aims: Safety of aspirin-free strategy immediately after percutaneous coronary intervention (PCI) for cardiovascular events in patients with diabetes was unknown., Methods and Results: We conducted the prespecified subgroup analysis on diabetes in the STOPDAPT-3 trial, which randomly compared prasugrel (3.75 mg/day) monotherapy (2984 patients) to dual antiplatelet therapy (DAPT) with prasugrel and aspirin (2982 patients) in patients with acute coronary syndrome or high bleeding risk. The co-primary endpoints were major bleeding events (Bleeding Academic Research Consortium 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) at 1 month. Of 5966 study patients, there were 2715 patients (45.5%) with diabetes. Patients with diabetes more often had chronic coronary syndrome, heart failure or cardiogenic shock, and comorbidities than those without. Patients with diabetes compared to those without had higher incidences of major bleeding and cardiovascular events. Regardless of diabetes, the effect of no-aspirin relative to DAPT was not different for the co-primary bleeding (diabetes: 5.05% vs. 5.47%; HR, 0.92; 95%CI, 0.66-1.28 and non-diabetes: 3.99% vs. 4.07%; HR, 0.98; 95%CI, 0.69-1.38; P for interaction = 0.81) and cardiovascular (diabetes: 5.54% vs. 5.15%; HR, 1.08; 95%CI, 0.78-1.49 and non-diabetes: 2.95% vs. 2.47%; HR, 1.20; 95%CI, 0.79-1.82; P for interaction = 0.70) endpoints. The incidences of subacute definite or probable stent thrombosis and any coronary revascularization were higher in the no-aspirin group than in the DAPT group regardless of diabetes., Conclusions: The effects of an aspirin-free prasugrel monotherapy (3.75 mg/day) relative to DAPT for major bleeding and cardiovascular events were not different regardless of diabetes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: Current guidelines recommend the use of glycoprotein IIb/IIIa (GpIIb/IIIa) inhibitors in patients with ST-segment elevation myocardial infarction (STEMI) only as a bail-out therapy. However, drug penetration to the jeopardised area may not be achieved due to impeded blood flow and increased microvascular resistance. Aim of our study is to investigate the impact of distal intracoronary GpIIb/IIIa inhibitor agent infusion in STEMI patients. Primary endpoints were microvascular obstruction (MVO) and infarct size., Methods: Patients with STEMI who have high thrombus burden or slow-flow/NR phenomenon and undergoing primary percutaneous coronary intervention (pPCI) were enrolled. Tirofiban was the preferred GpIIb/IIIa inhibitor. Patients were assigned to the systemic intravenous infusion group and intracoronary infusion group in whom bolus dose of tirofiban was distally infused to the infarct related artery. MVO and size of the infarct size were assessed via cardiac MRI., Results: We prospectively included 75 patients and mean follow-up duration was 383 days. Baseline characteristics were similar between groups except a lower rate of diabetes in distal intracoronary infusion group ( p  = .006). There was no significant difference in localisation of myocardial infarction, ischaemia duration and preloading of P2Y12 inhibitor between groups. MVO ( p  = .048) and infarct size ( p  = .030) were significantly lower in distal intracoronary infusion group., Conclusions: Cardiac MRI based assessment revealed that intracoronary administration of GpIIb/IIIa inhibitors distal to the culprit lesion was associated with reduced MVO and infarct size in high thrombotic risk STEMI patients undergoing pPCI.

Background: Reversing heparin when managing coronary artery perforation (CAP) during percutaneous coronary intervention (PCI) can provide hemostasis but may cause coronary thrombosis if a device is still present in a coronary artery., Aims: To assess the impact of heparin reversal while an intracoronary artery device is in place for CAP., Methods: This study analyzed CAP cases during PCI from January 2006 to October 2023. Patients were grouped according to implementing heparin reversal while an intracoronary artery device was in place. The safety outcome was coronary thrombosis after CAP. The efficacy outcomes were successful hemostasis and death from any cause., Results: CAP occurred in 368 of 22,368 cases (1.6%). Patients who had heparin reversal with a device in place comprised 211 (57%). Among these, coronary thrombosis occurred in 16 (7.6%). An activated clotting time (ACT) 〈150 seconds was significantly correlated with coronary thrombosis. Heparin reversal with a device in place was significantly associated with successful hemostasis (heparin reversal 91% vs. no heparin reversal 73%; adjusted odds ratio 2.78; 95% confidence interval 1.27-6.13; p = 0.011), but was not different for death from any cause (heparin reversal 4.3% vs. no heparin reversal 5.7%; adjusted odds ratio 0.97; 95% confidence interval 0.28-3.43; p = 0.964)., Conclusion: Heparin reversal with a device in place was associated with an increased risk of coronary thrombosis when ACT was less than 150 seconds. While it may not have a substantial association with a reduced risk of mortality, it offers an advantage in achieving successful hemostasis., (© 2024 Wiley Periodicals LLC.)

Introduction: Advances in pharmacotherapy for coronary thrombosis treatment and prevention have transformed the clinical outcomes of patients with coronary artery disease but increased the complexity of therapeutic decision-making. Improvements in percutaneous coronary intervention techniques and stent design have reduced the incidence of thrombotic complications, which consequently has increased the challenge of adequately powering clinical trials of novel antithrombotic strategies for efficacy outcomes. Knowledge of the pathophysiology of coronary thrombosis and the characteristics of antithrombotic drugs can help with therapeutic decisions., Areas Covered: This review covers the pathophysiology of coronary thrombosis and the mechanisms of action of drugs developed for its treatment, provides an overview of the key issues in decision-making, and highlights key areas for further work in order to guide clinicians on how to individualize risk management and address gaps in the evidence base., Expert Opinion: Individualization of antithrombotic therapy regimens has become a vital part of optimizing risk management in people with coronary thrombosis. A critical appraisal of the strengths and limitations of available drugs and the evidence supporting the use of different antithrombotic combinations is intended to provide direction to clinicians and point the way toward further improvements in pharmacotherapy for coronary thrombosis treatment and prevention.

Since the advent of coronary stents, two of the most common long-term complications after percutaneous coronary intervention (PCI) are in-stent restenosis (ISR) and stent thrombosis (ST). Although the rates of ST have been nearly abolished and ISR rates have declined with the current gold-standard second-generation drug-eluting stents (DES), late ISR of DES remains a valid concern in the field of interventional cardiology. The drug-coated balloon (DCB) is a non-stent technology that relies on the concept of targeted homogeneous drug delivery from an inflated balloon to restore luminal vascularity, treat atherosclerosis, and overcome some limitations of PCI, including ISR and prolonged dual antiplatelet therapy to prevent ST by leaving nothing behind. Most clinical evidence on coronary DCBs predominantly comes from small, randomized data and registries using paclitaxel DCBs for ISR and de novo lesions in the coronary space. Since 2014, outside the United States, DCBs have been approved for the treatment of ISR, with a class I recommendation by the European Society of Cardiology. The Food and Drug Administration very recently approved the Agent DCB to treat ISR in patients with coronary artery disease in the US. Additionally, recent randomized clinical data also showed DCB's safety and efficacy for the treatment of de novo small-vessel disease and high-bleeding-risk patients, while their role for other clinical situations including acute coronary syndrome, large-vessel disease, bifurcation lesions, and long-diffuse distal lesions is currently under investigation. Herein, we review the evidence-based role of DCBs in the treatment of coronary lesions and offer future perspectives., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ron Waksman – Advisory Board: Abbott Vascular, Boston Scientific, Medtronic, Philips IGT, Pi-Cardia Ltd.; Consultant: Abbott Vascular, Append Medical, Biotronik, Boston Scientific, JC Medical, MedAlliance/Cordis, Medtronic, Philips IGT, Pi-Cardia Ltd., Swiss Interventional/SIS Medical AG, Transmural Systems Inc.; Institutional Grant Support: Biotronik, Medtronic, Philips IGT; Investor: Transmural Systems Inc. All other authors – None., (Copyright © 2024. Published by Elsevier Inc.)

Current evidence indicates that dual antiplatelet therapy with aspirin plus a P2Y 12 inhibitor is essential for the prevention of thrombotic events after percutaneous coronary interventions. However, dual antiplatelet therapy is associated with increased bleeding which may outweigh the benefits. This has set the foundations for customizing antiplatelet treatments to the individual patient. However, bleeding and ischemic risks are often present in the same patient, making it difficult to achieve this balance. The fact that oral P2Y 12 inhibitors (clopidogrel, prasugrel, and ticagrelor) have diverse pharmacodynamic profiles that affect clinical outcomes supports the rationale for using platelet function and genetic testing to individualize antiplatelet treatment regimens. Indeed, up to one-third of patients treated with clopidogrel, but a minority of those treated with prasugrel or ticagrelor, exhibit high residual platelet reactivity resulting in an increased thrombotic risk. On the other hand, prasugrel and ticagrelor are frequently associated with low platelet reactivity and increased bleeding risk compared with clopidogrel without providing any additional reduction in ischemic events compared with patients who adequately respond to clopidogrel. The use of platelet function and genetic testing may allow for a guided selection of oral P2Y 12 inhibitors. However, the nonuniform results of randomized controlled trials have led guidelines to provide limited recommendations on the implementation of these tests in patients undergoing percutaneous coronary intervention. In light of recent advancements in the field, this consensus document by a panel of international experts fills in the guideline gap by providing updates on the latest evidence in the field as well as recommendations for clinical practice., Competing Interests: Funding Support and Author Disclosures Dr Angiolillo has received consulting fees or honoraria from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, CSL Behring, Daiichi-Sankyo, Eli Lilly, Faraday, Haemonetics, Janssen, Merck, Novartis, Novo Nordisk, PhaseBio, PLx Pharma, Pfizer, and Sanofi; and his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Faraday, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, and the Scott R. MacKenzie Foundation. Dr Alexopoulos has received advisory board fees or honoraria from AstraZeneca, Bayer, Chiesi, and Pfizer; and institutional research grants from CSL Behring. Dr Aradi has received lecture fees from Amgen, AstraZeneca, Bayer AG, Biotronik, Boehringer, Egis, Krka, Medtronic, Novartis, Novo Nordisk, Pfizer, Richter Gedeon, and Vascular Venture. Dr Bhatt has served on the advisory board for Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, and Stasys; has served on the Board of Directors for American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock); has served as a consultant for Broadview Ventures, GlaxoSmithKline, Hims, SFJ, and Youngene; has served on Data Monitoring Committees for Acesion Pharma, Assistance Publique–Hôpitaux de Paris, the Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic, the Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi-Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical), Novartis, the Population Health Research Institute, Rutgers University (for the National Institutes of Health–funded MINT trial); has served as a Data Monitoring Committee chair for Boston Scientific (PEITHO trial) and Contego Medical (PERFORMANCE 2); has received honoraria from American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), the Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), the Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (American Heart Association lecture), Cowen and Company, the Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), JACC (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (continuing medical education steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and U.S. national co-leader, funded by Bayer), WebMD (continuing medical education steering committees), and Wiley (steering committee); has served as the Deputy Editor for Clinical Cardiology; owns a patent for Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon; neither Dr Bhatt nor Brigham and Women's Hospital receives any income from this patent); has received research funding from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; has received royalties from Elsevier (Editor, Braunwald’s Heart Disease); has served as a Site Co-Investigator for Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; has been a trustee of the American College of Cardiology; and has conducted unfunded research for FlowCo. Dr Bonello’s his institution received payment from INARI, Boston Scientific, Abbott, Biotronik, and Bristol Myers Squibb. Dr Capodanno has received payment as an individual for consulting fees or honoraria from Sanofi. Dr Cavallari has received research support from Werfen. Dr Cuisset has received consulting and lecture fees from Abbott Vascular, Boston Scientific, Edwards Lifesciences, Europa Organisation, Medtronic, Terumo, and Sanofi. Dr Ferreiro has received lecture honoraria from Eli Lilly, Daiichi-Sankyo, AstraZeneca, Pfizer, Abbott, Boehringer Ingelheim, Bristol Myers Squibb, Rovi, Terumo and Ferrer; consulting fees from AstraZeneca, Eli Lilly, Ferrer, Boston Scientific, Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Bristol Myers Squibb, and Biotronik; and research grants from AstraZeneca. Dr Franchi has received payment as an individual for consulting fees or honoraria from AstraZeneca; and institutional payments for grants from PLx Pharma and the Scott R. MacKenzie Foundation. Dr Geisler has received lecture honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Ferrer/Chiesi, Novartis, and Pfizer; consulting fees from AstraZeneca, Bristol Myers Squibb, Ferrer, Edwards Lifesciences, Haemonetics, and Pfizer; and research grants from Bayer, Bristol Myers Squibb/Pfizer, Ferrer/Chiesi, Medtronic, and Edwards Lifesciences. Dr Gibson has received grants from SCAD Alliance, Johnson & Johnson, Janssen, and CSL Behring; has received personal fees from Bayer, AstraZeneca (during the conduct of the study), Angel Medical Corporation, CSL Behring, Janssen, Johnson & Johnson, the Boston Clinical Research Institute, the Cardiovascular Research Foundation, Gilead Sciences, WebMD, UpToDate in Cardiovascular Medicine, Somahlution, Boston Scientific, the Duke Clinical Research Institute, Medtelligence, Microport, PERT Consortium, Caladrius Biosciences, CeleCor Therapeutics, Eidos Therapeutics, Microdrop, MD Magazine, the Society for Cardiovascular Angiography and Interventions, Revance Therapeutics, Pfizer, Dyad Medical, CytoSorbents, AMAG Pharmaceuticals, Bristol Myers Squibb, Amarin, PhaseBio, Bioclinica, Inari, MedImmune, PLx Pharma, Merck, Paratek, Anthos Therapeutics, PHRI, SmartMedics, EXCITE International ($0 received), Novo Nordisk, MedTrace, and the Cardiovascular Clinical Science Foundation; has received nonfinancial support from the Baim Institute; and owns equity in nference, Absolutys, and Dyad Medical. Dr Gorog has received institutional research grants from Bayer, AstraZeneca, Medtronic, and Werfen; and personal fees from Janssen, Bristol Myers Squibb, and Chiesi. Dr Gurbel has received consulting fees and/or honoraria from Bayer, Vectura/Otitopic, Janssen, Cleveland Clinic Foundation, Wolters Kluwer Pharma, Web MD Medscape, Baron and Budd, Premier Health Care Resource, Baim Institute, and Medforce; has received institutional research grants from Accriva Diagnostics, AstraZeneca, Bayer, Cronos, Janssen Pharmaceuticals Inc., Haemonetics, Hikari Dx, Idorisa, Labcorp Drug Development, Novartis, Prolocor, Recor Medical, Vectura Limited, and Zoll Medical Corporation; owns 2 patents (Detection of restenosis risk in patients issued and Assessment of cardiac health and thrombotic risk in a patient); has served as an expert witness in a lawsuit associated with Plavix. Dr Jeong has received honoraria for lectures from Daiichi-Sankyo, Sanofi, Han-mi Pharmaceuticals, and Daewoong Pharmaceuticals; and research grants or support from Samjin Pharmaceuticals, Hanmi Pharmaceuticals, Yuhan Pharmaceuticals, Biotronik Korea, and U and I Corporation. Dr Marcucci has received consulting fees or honoraria from Amgen, AstraZeneca, Bayer, Daiichi-Sankyo, Novartis, Sanofi, Viatris, and Werfen. Dr Siller-Matula has received speaker or consulting fees from AOP, Chiesi, Biosensors, Boston Scientific, P&F, Boehringer Ingelheim, and Daiichi-Sankyo not related to the submitted work. Dr Mehran has received institutional research payments from Abbott, Abiomed, Alleviant Medical, AM-Pharma, Amgen, Arena, AstraZeneca, Atricure, Bayer, Biosensors, Biotronik, Boston Scientific, Bristol Myers Squibb, CardiaWave, CeloNova, Chiesi, Concept Medical, CSL Behring, Cytosorbents, Daiichi-Sankyo, Element Science, Faraday, Humacyte, Idorsia Pharmaceuticals, Janssen, Medtronic, Novartis, OrbusNeich, PhaseBio, Philips, Pi-Cardia, RenalPro, Shockwave, Vivasure, and Zoll; has received personal fees from Cine-Med Research and WebMD; owns equity (<1%) in Applied Therapeutics, Elixir Medical, Stel, and ControlRad (via her spouse); has served on the Scientific Advisory Board for the American Medical Association, the American College of Cardiology (Board of Trustees Member), the Society for Cardiovascular Angiography and Interventions (Women in Innovations Committee Member), and JAMA (Associate Editor); and has served as faculty for the Cardiovascular Research Foundation (no fee). Dr Neumann has received consulting honoraria from Novartis and Meril; speaker honoraria from Boston Scientific, Amgen, Daiichi-Sankyo, and Meril; speaker honoraria paid to his institution from Bristol Myers Squibb/Pfizer, Daiichi-Sankyo, Boston Scientific, Siemens, and Amgen; and research grants paid to his institution from Boston Scientific and Abbott. Dr So has received consulting fees or honoraria from Abbott Vascular, AstraZeneca, Bayer, HLS Therapeutics, JAMP Pharma Corp, Medtronic, and DYFS; and received research grants from Aggredyne, Diapharma, Eli Lilly, Fujimori Kogyo, Roche Diagnostics, and Spartan Biosciences. Dr Stone has received speaker honoraria from Medtronic, Pulnovo, Infraredx, Abiomed, Amgen, and Boehringer Ingelheim; served as a consultant for Abbott, Daiichi-Sankyo, Ablative Solutions, CorFlow, Cardiomech, Robocath, Miracor, Vectorious, Abiomed, Valfix, Apollo Therapeutics, Elucid Bio, Cardiac Success, TherOx, HeartFlow, Neovasc, Ancora, Occlutech, Impulse Dynamics, Adona Medical, Millennia Biopharma, Oxitope, HighLife, Elixir, Remote Cardiac Enablement, and Aria; he owns equity/options in Cardiac Success, Ancora, Cagent, Applied Therapeutics, and Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Valfix, and Xenter; and his employer (Mount Sinai Hospital) has received research grants from Shockwave, Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, Biosense Webster, Vascular Dynamics, Pulnovo, and V-wave. Dr Storey has received institutional research grants/support from AstraZeneca and Cytosorbents; and personal fees from Alfasigma, AstraZeneca, Boehringer Ingelheim/Lilly, Chiesi, Cytosorbents, Daiichi-Sankyo, Idorsia, Novartis, Novo Nordisk, Pfizer, PhaseBio, and Tabuk. Dr Tantry has received honoraria from Wolters Kluwer Pharma. Dr ten Berg has received institutional research grants from ZonMw (Dutch Government) and Daiichi-Sankyo; has served on the advisory board CeleCor; and has received lecture and advisory board fees paid to his institution from AstraZeneca, Bristol Myers Squibb, and Pfizer. Dr Trenk has received honoraria for lectures from AstraZeneca, Daiichi-Sankyo, and Novartis; and consulting fees from Atriva, Daiichi-Sankyo, and Eleva. Dr Valgimigli has received personal fees from AstraZeneca, Terumo, Alvimedica/CID, Abbott Vascular, Daiichi-Sankyo, Bayer, CoreFLOW, Idorsia Pharmaceuticals Ltd, Universität Basel | Dept. Klinische Forschung, Bristol Myers Squibb SA/Janssen, Medscape, Biotronik, Novartis, and Vesalio, outside the submitted work; and grants from Terumo, outside the submitted work. Dr Waksman has served on advisory boards for Abbott Vascular, Boston Scientific, J Valve, Medtronic Inc, Philips IGT, and Pi-Cardia Ltd.; has served as a consultant for Abbott Vascular, Biotronik, Boston Scientific, CardioMed LLC, Cordis, Medtronic Inc, Philips IGT, Pi-Cardia Ltd., Swiss Interventional Systems/SIS Medical AG, Transmural Systems Inc., and Venous MedTech; has received institutional grant support from Amgen, Biotronik, Boston Scientific, Chiesi, Medtronic Inc, and Philips IGT; and is an investor in MedAlliance, Pi-Cardia Ltd., and Transmural Systems. Dr Sibbing has received speaker fees and fees for advisory board activities from Bayer, Sanofi, and Daiichi-Sankyo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: We conducted a prespecified subanalysis of the POEM trial to assess the association between sex and clinical outcomes following a short 1-month dual-antiplatelet-therapy (DAPT) period after percutaneous coronary intervention (PCI) with bioresorbable polymer everolimus-eluting stent (BP-EES) among patients at high bleeding risk (HBR)., Background: Shortening the DAPT period after PCI is an effective bleeding avoidance strategy with contemporary drug-eluting stents. Whether sex affects the risk of adverse events following PCI is still debated., Methods: Patients at HBR undergoing PCI with BP-EES were enrolled and treated with 1-month DAPT. If anticoagulation was needed, study participants received an oral anticoagulant (OAC) in addition to a P2Y 12 inhibitor for 1 month, followed by OAC only thereafter. The primary endpoint was a composite of cardiac death, myocardial infarction, or definite/probable stent thrombosis at 12 months. We report sex-based outcomes of patients included in the POEM study., Results: We enrolled 129 (29.1%) women and 314 (70.9%) men. Women were older, with lower hemoglobin levels, and worse renal function. Accordingly, they had a trend for a greater number of HBR criteria fulfilled and a higher PARIS bleeding score. However, they were not at a significantly higher risk for the primary endpoint (men vs. women: 5.17% vs. 3.94%; HR 1.30; 95% CI: 0.48-3.54, p = 0.61), or any of the hemorrhagic and ischemic secondary endpoints., Conclusions: This prespecified subanalysis of the POEM trial suggests that 1-month DAPT following PCI with BP-EES may be a safe and effective therapeutic strategy for women at HBR., (© 2024 The Author(s). Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is fundamental in all patients undergoing percutaneous coronary intervention (PCI) to prevent coronary thrombosis. In patients with atrial fibrillation (AF), an oral anticoagulant gives protection against ischemic stroke or systemic embolism. AF-PCI patients are at high bleeding risk and decision-making regarding the optimal antithrombotic therapy remains challenging. Dual antithrombotic therapy (DAT) has been shown to reduce bleeding events but at the cost of a higher risk of stent thrombosis. Further studies are needed to clarify the optimal duration of triple antithrombotic therapy (TAT) or DAT and the role of more potent antiplatelet drugs., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Previous studies have investigated a 1 to 6-month short dual antiplatelet therapy (S-DAPT) after percutaneous coronary intervention (PCI) with modern drug eluting-stents to reduce bleeding events., Objectives: To investigate cardiovascular outcomes in patients at high bleeding risk (HBR) according to the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria after PCI with the Synergy bioresorbable-polymer everolimus-eluting stents (EES)., Methods: We applied ARC-HBR criteria in the population of the prospective, single-arm, multicenter POEM (Performance of Bioresorbable Polymer-Coated Everolimus-Eluting Synergy Stent in Patients at HBR Undergoing Percutaneous Coronary Revascularization Followed by 1-Month Dual Antiplatelet Therapy) trial. The primary endpoint was a composite of cardiac death, myocardial infarction, or definite or probable stent thrombosis at 12 months., Results: The original POEM cohort included 356 patients (80.4 %) fulfilling ARC-HBR criteria. Oral anticoagulant (OAC) usage and age ≥75 years were the most frequent major and minor ARC-HBR criteria, respectively. The ARC-HBR group was mainly represented by men (71.1 %), with 74.4 ± 9.3 years and a high burden of cardiovascular risk factors. DAPT was prescribed in 79.3 %, and single antiplatelet (SAPT) with OAC in 18.7 %. 12-month follow-up was completed in 96.2 %. The primary endpoint occurred in 5.2 % (95 % CI 3.29-8.10) of patients, whereas bleeding Academic Research Consortium type 3-5 occurred in 2.7 % (95 % CI, 1.39 %-5.05 %)., Conclusion: Previous results of the POEM trial showed positive outcomes regarding ischemic and bleeding events with an S-DAPT regimen after Synergy EES. These results are also confirmed in sub-group analysis when ARC-HBR criteria are applied., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Patients with an indication for oral anticoagulation who undergo percutaneous coronary intervention require a combination of oral anticoagulation and antiplatelet therapy. The use of a coronary stent with a thromboresistant and pro-healing coating may allow an abbreviated duration of dual antiplatelet therapy (DAPT) without an increase in the risk of thromboembolic events., Methods: Patients with an indication for oral anticoagulation undergoing percutaneous coronary intervention were randomized to treatment with the COBRA polyzene F (PzF) stent followed by 14 days of DAPT or a Food and Drug Administration-approved new-generation drug-eluting stent followed by 3 or 6 months of DAPT. The bleeding coprimary end point was Bleeding Academic Research Consortium type ≥2 beyond 14 days (or after hospital discharge) until 6 months. The thromboembolic coprimary end point was the composite of all-cause death, myocardial infarction, definite or probable stent thrombosis, or ischemic stroke at 6 months. The trial hypothesis was that the COBRA PzF stent strategy would be superior with respect to bleeding events and noninferior with respect to thromboembolic events., Results: A total of 996 patients underwent randomization. The bleeding end point occurred in 37 of 475 patients (7.8%) in the COBRA PzF group and 47 of 482 patients (9.8%) in the control group (difference, -2.0 [95% CI, -5.6 to 1.6]; P =0.14). The thromboembolic end point occurred in 37 of 492 patients (7.5%) in the COBRA PzF group and 24 of 490 patients (4.9%) in the control group (difference, 2.6%; prespecified noninferiority margin 5%, upper limit of 1-sided 95% CI of the difference, 5.2%; P noninferiority =0.07)., Conclusions: In patients with an indication for oral anticoagulation undergoing percutaneous coronary intervention, treatment with the COBRA PzF stent plus 14 days of DAPT was not superior with respect to bleeding events and was not noninferior with respect to thromboembolic events at 6 months compared with treatment with standard Food and Drug Administration-approved drug-eluting stent plus 3 to 6 months of DAPT., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02594501., Competing Interests: Dr Byrne reports research or educational funding to the institution of current employment from Abbott Vascular, Biosensors, Boston Scientific, and Translumina. Dr Maeng is supported by a grant from the Novo Nordisk Foundation (grant number NNF22OC0074083), has received lecture and advisory board fees from Astra-Zeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, and Novo Nordisk, has received research grants from Philips, Bayer, and Novo Nordisk, has ongoing research contracts with Novo Nordisk and Philips, and is a minor shareholder in Eli Lilly and Novo Nordisk. Dr Brunner is a previous employee of CeloNova. Dr Urban reports personal consulting fees from and is a shareholder of MedAlliance, Nyon, Switzerland, outside of the submitted work. Dr Cutlip reports contracted research support paid to institution of current employment from Celonova. Dr Kirtane reports Institutional funding to Columbia University and/or Cardiovascular Research Foundation from Medtronic, Boston Scientific, Abbott Vascular, Amgen, CathWorks, Cardiovascular Systems Inc, Philips, ReCor Medical, Neurotronic, Biotronik, Chiesi, Bolt Medical, Magenta Medical, Canon, SoniVie, and Shockwave Medical. In addition to research grants, institutional funding includes fees paid to Columbia University and/or Cardiovascular Research Foundation for consulting and/or speaking engagements in which Dr Kirtane controlled the content. Personal: Travel Expenses/Meals from Amgen, Medtronic, Biotronik, Boston Scientific, Abbott Vascular, CathWorks, Edwards, Cardiovascular Systems Inc, Novartis, Philips, Abiomed, ReCor Medical, Chiesi, Zoll, Shockwave, and Regeneron. The other authors report no conflicts.

Dual antiplatelet therapy (DAPT) remains the gold standard in patients who underwent percutaneous coronary intervention (PCI). This meta-analysis aims to evaluate the clinical safety of 1-month DAPT followed by aspirin or a P2Y12 receptor inhibitor after PCI with drug-eluting stents (DES). We searched PubMed, MEDLINE, Embase, Scopus, Google Scholar, Cochrane Central Registry, and ClinicalTrials.gov databases and identified 5 randomized controlled trials with 29,831 patients who underwent PCI with DES and compared 1-month versus >1-month DAPT. The primary end point was major bleeding, and the co-primary end point was stent thrombosis. The secondary end point included all-cause mortality, cardiovascular death, myocardial infarction, stroke, and major adverse cardiovascular or cerebrovascular events. Compared with >1-month DAPT, the 1-month DAPT was associated with a lower rate of major bleeding (odds ratio [OR] 0.66, 95% confidence interval [CI] 0.45 to 0.97, p = 0.03, I 2 = 71%), whereas stent thrombosis had a similar rate in both study groups (OR 1.08, 95% CI 0.81 to 1.44, p = 0.60, I 2 = 0.0%). The study groups had similar risks for all-cause mortality (OR 0.89, 95% CI 0.77 to 1.04, p = 0.14, I 2 = 0.0%), cardiovascular death (OR 0.84, 95% CI 0.59 to 1.19, p = 0.32, I 2 = 0.0%), myocardial infarction (OR 1.04, 95% CI 0.89 to 1.21, p = 0.62, I 2 = 0.0%), and stroke (OR 0.82, 95% CI 0.64 to 1.05, p = 0.11, I 2 = 6%). The risk of major adverse cardiovascular or cerebrovascular events was lower (OR 0.86, 95% CI 0.76 to 0.97, p = 0.02, I 2 = 25%) in the 1-month DAPT compared with >1-month DAPT. In conclusion, in patients who underwent PCI with DES, 1-month DAPT followed by aspirin or a P2Y12 receptor inhibitor reduced major bleeding with no risk of increased thrombotic risk compared with longer-term DAPT., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Diabetes mellitus is associated with higher risk of target lesion failure (TLF) after percutaneous coronary intervention. We studied the 5-year outcome in patients with diabetes mellitus treated with biodegradable polymer stents., Methods: The SORT OUT VII was a randomised trial comparing the ultrathin sirolimus-eluting Orsiro stent (O-SES) and the biolimus-eluting Nobori stent (N-BES) in an all-comer setting. Patients ( n = 2525) were randomised to receive O-SES ( n = 1261, diabetes: n = 236) or N-BES ( n = 1264, diabetes: n = 235). Endpoints were TLF (a composite of cardiac death, target-lesion myocardial infarction (MI), target lesion revascularization (TLR)), definite stent thrombosis and a patient related outcome (all-cause mortality, MI and revascularization) within 5 years., Results: Patients with diabetes mellitus had higher TLF (20.6% vs 11.0%, (Rate ratio (RR) 1.85 95% confidence interval (CI): (1.42-2.40) and patient related outcome (42.0% vs 31.0%, RR 1.43 95% CI: (1.19-1.71)) compared to patients without diabetes. Among patients with diabetes mellitus, TLF after 5 years did not differ between O-SES and N-BES (21.2% vs 20.0%), RR 1.05 95% CI: (0.70-1.58), p = 0.81). Cardiac death, MI, TLR, and definite stent thrombosis did not differ between the groups., Conclusion: In patients with diabetes mellitus, 5-year outcomes were similar among patients treated with biodegradable polymer O-SES or N-BES., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01879358., Competing Interests: Declaration of conflicting interestsThe author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: LOJ has received research grants from Biotronik and Biosensor to her institution, MKC has received both educational and research grants from Biotronik and Terumo. MM is supported by a grant from the Novo Nordisk Foundation (grant number NNF22OC0074083); has received lecture and/or advisory board fees from AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, and Novo Nordisk, has received a travel grant from Novo Nordisk, has received institutional research grants from Philips, Bayer and Novo Nordisk, has ongoing research contracts with Janssen, Novo Nordisk, and Philips, and equity in Novo Nordisk, Eli Lilly & Company, and Verve Therapeutics. JT, EHC, KNH, AE, LJ, MM, PF, RVJ, MN, JEG, NBS, JK and KTV declare they have no conflicts of interest.

Background: There was no study evaluating the effects of an aspirin-free strategy in patients undergoing complex percutaneous coronary intervention (PCI)., Objectives: The authors aimed to evaluate the efficacy and safety of an aspirin-free strategy in patients undergoing complex PCI., Methods: We conducted the prespecified subgroup analysis based on complex PCI in the STOPDAPT-3 (ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3), which randomly compared low-dose prasugrel (3.75 mg/d) monotherapy to dual antiplatelet therapy (DAPT) with low-dose prasugrel and aspirin in patients with acute coronary syndrome or high bleeding risk. Complex PCI was defined as any of the following 6 criteria: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or a target of chronic total occlusion. The coprimary endpoints were major bleeding events (Bleeding Academic Research Consortium 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) at 1 month., Results: Of the 5,966 study patients, there were 1,230 patients (20.6%) with complex PCI. Regardless of complex PCI, the effects of no aspirin relative to DAPT were not significant for the coprimary bleeding (complex PCI: 5.30% vs 3.70%; HR: 1.44; 95% CI: 0.84-2.47; P = 0.18 and noncomplex PCI: 4.26% vs 4.97%; HR: 0.85; 95% CI: 0.65-1.11; P = 0.24; P for interaction = 0.08) and cardiovascular (complex PCI: 5.78% vs 5.93%; HR: 0.98; 95% CI: 0.62-1.55; P = 0.92 and noncomplex PCI: 3.70% vs 3.10%; HR: 1.20; 95% CI: 0.88-1.63; P = 0.25; P for interaction = 0.48) endpoints without significant interactions., Conclusions: The effects of the aspirin-free strategy relative to standard DAPT for the cardiovascular and major bleeding events were not different regardless of complex PCI. (ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3 [STOPDAPT-3]; NCT04609111)., Competing Interests: Funding Support and Author Disclosures This study was funded by Abbott Medical Japan. Dr Natsuaki has received honoraria from Abbott Medical Japan, Daiichi-Sankyo, Medtronic, Terumo, Japan Lifeline, Asahi Intecc, Bristol Myers Squibb, Otsuka, Amgen, Sanofi, Takeda, and Bayer. Dr Watanabe has received personal fees from Abbott Medical Japan during the conduct of the study as well as personal fees from Daiichi-Sankyo, Kowa, Abiomed, Bayer, Pfizer, Bristol Myers Squibb, and Otsuka outside the submitted work. Dr Morimoto has received lecturer fees from AstraZeneca, Bristol Myers Squibb, Daiichi-Sankyo, Japan Lifeline, Kowa, Pfizer, and Tsumura; has received manuscript fees from Bristol Myers Squibb and Pfizer; and has served on the Advisory Boards for Novartis and Teijin. Dr Suwa has received personal fees from Abbott Medical Japan and Daiichi-Sankyo outside the submitted work. Dr Kimura has received grants from Abbott Medical Japan and Boston Scientific; and has served on the Advisory Boards of Abbott Medical Japan and Terumo Japan. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to investigate a therapeutic approach targeting the inflammatory response and consequent remodeling from ischemic myocardial injury., Methods and Results: Coronary thrombus aspirates were collected from patients at the time of ST-segment-elevation myocardial infarction and subjected to array-based proteome analysis. Clinically indistinguishable at myocardial infarction (MI), patients were stratified into vulnerable and resilient on the basis of 1-year left ventricular ejection fraction and death. Network analysis from coronary aspirates revealed prioritization of tumor necrosis factor-α signaling in patients with worse clinical outcomes. Infliximab, a tumor necrosis factor-α inhibitor, was infused intravenously at reperfusion in a porcine MI model to assess whether infliximab-mediated immune modulation impacts post-MI injury. At 3 days after MI (n=7), infliximab infusion increased proregenerative M2 macrophages in the myocardial border zone as quantified by immunofluorescence (24.1%±23.3% in infliximab versus 9.29%±8.7% in sham; P <0.01). Concomitantly, immunoassays of coronary sinus samples quantified lower troponin I levels (41.72±7.34 pg/mL versus 58.11±10.75 pg/mL; P <0.05) and secreted protein analysis revealed upregulation of injury-modifying interleukin-2, -4, -10, -12, and -18 cytokines in the infliximab-treated cohort. At 4 weeks (n=12), infliximab treatment resulted in significant protective influence, improving left ventricular ejection fraction (53.9%±5.4% versus 36.2%±5.3%; P <0.001) and reducing scar size (8.31%±10.9% versus 17.41%±12.5%; P <0.05)., Conclusions: Profiling of coronary thrombus aspirates in patients with ST-segment-elevation MI revealed highest association for tumor necrosis factor-α in injury risk. Infliximab-mediated immune modulation offers an actionable pathway to alter MI-induced inflammatory response, preserving contractility and limiting adverse structural remodeling.

Introduction: Among different coronary stents implanted in High Bleeding Risk (HBR) patients with an indication for short antiplatelet therapy, no comparisons in terms of efficacy have been provided., Methods: A Network Meta Analysis was performed including all randomized controlled trials comparing different coronary stents evaluated in HBR patients. Major Adverse Cardiovascular Events (MACEs) as defined by each included trial were the primary end point, whereas TLR (target lesion revascularization), TVR (target vessel revascularization), stent thrombosis and total and major (BARC3-5) bleedings were the secondary ones., Results: A total of four studies (ONYX ONE, LEADERS FREE, SENIOR and HBR in BIO-RESORT) including 6637 patients were analyzed with different kind of stents and dual antiplatelet therapy (DAPT) length (1 or 6 months) on 12 months follow-up. About one-third of these patients were defined HBR due to indication for oral anticoagulation. All drug eluting stents (DESs) reduced risk of MACE compared to Bare Metal Stents (BMSs) when followed by a 1-month DAPT. At SUCRA analysis, Orsiro was the device with the highest probability of performing best. Rates of TLR and TVR were significantly lower when using Resolute Onyx, Synergy and BioFreedom stents in comparison to BMS when followed by 1-month DAPT, with Synergy ranking best. Synergy also showed a significantly lower number of stent thrombosis compared to BMS (RR 0.28, 95% CI 0.06-0.93), while Orsiro and Resolute Integrity showed the highest probability of performing best., Conclusion: In HBRs patients, all DESs were superior to BMSs in terms of efficacy and safety. Among DESs, Orsiro was the one with the highest ranking in terms of MACE, mainly driven by a reduced incidence of repeated revascularization and stent thrombosis., (© 2024 Wiley Periodicals LLC.)

Background: Stent thrombosis is a rare but deleterious event. Routine coronary angiography with percutaneous coronary intervention (PCI) is often deferred in the presence of laboratory markers of acute inflammation to prevent complications. The aim of this study was to investigate whether an acute inflammatory state is associated with an increased risk of early stent thrombosis., Methods and Results: Within a prospective single-center registry, the association between preprocedural acute inflammatory activation, defined as C-reactive protein plasma levels >50 mg/L or a leukocyte count >12 g/L, and occurrence of early (≤30 days) stent thrombosis was evaluated. In total, 11 327 patients underwent PCI and of those, 6880 patients had laboratory results available. 49.6% of the study population received PCI for an acute coronary syndrome and 50.4% for stable ischemic heart disease. In patients with signs of acute inflammatory activation (24.9%), PCI was associated with a significantly increased risk for stent thrombosis (hazard ratio, 2.89; P <0.00001), independent of age, sex, kidney function, number and type of stents, presence of multivessel disease, choice of P2Y12 inhibitor, and clinical presentation. Elevated laboratory markers of acute inflammation were associated with the occurrence of stent thrombosis in both patients with acute coronary syndrome (hazard ratio, 2.63; P <0.001) and in patients with stable ischemic heart disease (hazard ratio, 3.57; P <0.001)., Conclusions: An acute inflammatory state at the time of PCI was associated with a significantly increased risk of early stent thrombosis. Evidence of acute inflammation should result in deferred PCI in elective patients, while future studies are needed for patients with acute coronary syndrome.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been demonstrated as a major risk factor in inducing coronary stent thrombosis due to its propensity to create a pro-thrombotic state. This review explores the mechanisms that may contribute to the increased thrombosis risk seen in COVID-19. Furthermore, we discuss the patient and haematological factors that predispose to an increased risk of stent thrombosis, as well as the role of certain antiplatelet and anticoagulation therapies, including ticagrelor and enoxaparin, that may reduce the likelihood and severity of in-stent thrombosis, in SARS-CoV-2 infection. To counter the proinflammatory and pro-thrombotic state shown in COVID-19, anti-thrombotic therapy in the future may be optimised using point-of-care platelet inhibition testing and inflammation-modifying therapies. Large-scale randomised trials with long-term follow-up are increasingly necessary to assess the intersection of COVID-19 and stent optimisation as well as the reduction of stent thrombosis after drug-eluting stent (DES) implantation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Competing Interests: Competing interests: RFS reports institutional research grants/support from AstraZeneca, GlyCardial Diagnostics and Thromboserin; consultancy fees from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb/Pfizer, Cytosorbents, GlyCardial Diagnostics, Haemonetics, Portola and Thromboserin; and honoraria from AstraZeneca, Bayer, Bristol Myers Squibb/Pfizer and Medscape.

We describe the case of a healthy patient with moderate COVID-19 infection without thrombophilia nor coronary disease background who presented with a relapsing thrombotic occlusion of the right coronary artery despite normal oxygenation, adequate antiaggregation and prophylactic anticoagulation. Prophylactic anticoagulation recommendations in COVID-19 were inadequate for this patient. Further data are needed to propose full-dose therapeutic anticoagulation for patients with coronary thrombosis and COVID-19 infection. This could nevertheless be considered even in mild forms of COVID-19., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: In new generation drug eluting stents (DESs) era, the impact of stent geometry on freedom from recurrent events has been poorly explored. Impact of struts thickness and the number of crowns and connectors on clinical outcomes were evaluated in the present study., Methods: Randomized controlled trials comparing last generation DESs were selected. The primary endpoint was the rate of target lesion revascularization (TLR), while secondary was definite stent thrombosis (ST)., Results: Fifty-three studies with 52,006 patients were included. A struts thickness ≤81 nm was associated with a lower incidence of TLR (2.9%: 2.4-3.4 vs. 3.6%: 3.0-4.3) and ST (0.8%: 0.6-1.1 vs. 1.3%: 0.9-1.8). A mean number of connectors >2.5 was also associated with a lower incidence of TLR (3.2%: 2.8-3.6 vs. 3.5%: 2.9-4.2) and ST (1.0%:0.8-1.3 vs. 1.3%: 0.9-1.7 vs. for ST). On the other hand, stents with average number of crowns <7.5 did not perform better than stents with higher average number of crowns., Conclusions: The findings of the study support that lower struts thickness and higher numbers of connectors have a positive clinical outcome reducing stent thrombosis and target lesion revascularizations, while the average number of stent crowns plays a secondary role., (© 2019 Wiley Periodicals, Inc.)

Objectives: We sought to evaluate the efficacy and safety of bivalirudin versus heparin in patients with coronary artery disease undergoing transradial artery coronary intervention (TRI)., Background: Bivalirudin and radial artery access are independently associated with improved cardiovascular outcomes. However, data supporting a strategy of combining both to achieve additive improvements in cardiovascular outcomes provide conflicting results., Methods: A systematic search was performed to identify randomized controlled trials (RCTs) of bivalirudin, in which vascular access sites were reported. The primary outcome was net adverse clinical events (NACE) at 30 days. Secondary outcomes were long-term NACE, short-, and long-term major adverse cardiovascular events, all-cause mortality, myocardial infarction, unplanned revascularization, stent thrombosis, and major bleeding., Results: We identified 10 RCTs, including 16,328 patients who underwent TRI (mean age 64.6 ± 15.7 years, 72.5% male). Bivalirudin use was associated with decreased 30-day NACE compared with heparin (6.3 vs. 7.4%; risk ratio [RR] = 0.87; 95% confidence interval [CI] = 0.76-0.99; p = .04; number needed to treat = 91). No significant interactions were observed based on clinical presentation, administration of P2Y 12 inhibitors, or glycoprotein IIb/IIIa-receptor inhibitors (GPI) use. There were no significant differences between groups in any prespecified secondary outcomes. There was, however, a significant reduction of major bleeding in the bivalirudin group compared with heparin when used in combination with routine GPI (RR = 0.41; 95% CI = 0.19-0.90; p = .03)., Conclusions: Among patients undergoing TRI, use of bivalirudin was associated with significantly reduced 30-day NACE compared with heparin. There was no significant difference in long term NACE, ischemic, or bleeding events compared with heparin., (© 2020 Wiley Periodicals, Inc.)

Objectives: We sought to answer whether 1-month duration of dual antiplatelet therapy (DAPT) is safe after elective drug-coated balloon only (DCB) angioplasty., Background: The duration of DAPT after elective DCB was called into question after the ESC Focused DAPT Update of 2017. Until then, a 1-month duration of DAPT was considered safe by national consensus groups (German, Italian, and Chinese) supported by data from prospective worldwide registries. The ESC Guidelines recommended a 6-month duration of DAPT based on evidence from in-stent restenosis randomized controlled trials only., Methods: Retrospective, real-world population, single-center analysis conducted from January 1, 2012 to March 31, 2017 in a high-volume, tertiary PCI center. Consecutive patients receiving 1-month duration of DAPT after elective DCB angioplasty were included. We identified a primary composite outcome of cardiac death, myocardial infarction and target lesion revascularization at 6-months., Results: A total of 303 patients (78.5% male) with mean age of 67 ± 12.5 were included. This incorporated 86.1% de novo lesions and 56.5% nonsmall (≥3 mm diameter) coronary arteries treated. There were no reported outcomes of lesion thrombosis, target vessel MI, target lesion revascularization or cardiac death at 6-months. There were two (0.6%) nontarget vessel MIs and one (0.3%) noncardiac death., Conclusion: One-month duration of DAPT appears safe after elective DCB-only angioplasty, highlighting this strategy for patients at high-risk of bleeding. These results also show favorable clinical outcomes for de novo coronary artery disease and nonsmall coronary arteries treated with DCB-only angioplasty. A 1-month duration of DAPT appears a safe and attractive option., (© 2019 Wiley Periodicals, Inc.)

Newer generation drug eluting stents (DES) and pharmacotherapy have decreased thrombotic events post-percutaneous coronary intervention (PCI). There is lack of wide-ranging safety and efficacy evaluation in both stable ischemic heart disease and acute coronary syndrome in short-term (3-6 months) versus Standard-term (12 months) dual antiplatelet therapy (DAPT). We searched electronic databases using specific terms to identify randomized control trials comparing different durations of DAPT after PCI with DES. The outcomes of interest included all-cause mortality, myocardial infarction, stent thrombosis, major bleeding, target lesion and vessel revascularization, and stroke at follow-up duration ≥12 months post index PCI. Studies that compared DAPT <3 months or DAPT ≥12 months were excluded. Thirteen randomized control trials (n = 31,831) were included; 8401 patients received DAPT for 3 months and 7482 patients received DAPT in the 6 months group. Major bleeding rate was lower in the short-term (3-6 months) versus Standard-term (12 months) group (risk ratio 0.66; 95% confidence interval, 0.52-0.84, P < 0.05). Repeat revascularization rate was higher in the short-term (3-6 months) versus Standard-term (12 months) (risk ratio 1.17; 95% confidence interval, 1.01-1.36, P < 0.05) of DAPT duration after PCI with DES. No difference in other outcomes were observed when comparing short versus standard duration of DAPT in both stable ischemic heart disease and acute coronary syndrome.

Purpose: To compare the effect of ticagrelor with clopidogrel in reducing the risk of ischemic cardiovascular events in patients with late or very late stent thrombosis (LST/VLST) after primary percutaneous coronary intervention (PCI)., Methods: A total of 4538 patients with acute coronary syndrome were screened for angiographically determined LST/VLST. Two hundred and forty-one patients were included in the analysis and grouped according to ticagrelor (n = 81) or clopidogrel (n = 160) at discharge. The clinical outcome was major adverse cardiovascular events (MACE) defined as death, myocardial infarction (MI), ischemic stroke, and revascularization during the 1-yr follow-up period., Results: After propensity score matching, 65 pairs were generated. The incidence of MACE was significantly lower in the ticagrelor group compared with the clopidogrel group (9.3% vs. 21.5%, log-rank p = 0.048). However, no difference was observed in event rates of death, MI, ischemic stroke, and revascularization between the ticagrelor group and the clopidogrel group., Conclusion: Following successful primary PCI, patients with LST/VLST who received ticagrelor had fewer ischemic cardiovascular events at 1-yr follow-up, compared with those who received clopidogrel.

Objectives: We sought to compare clinical outcomes after percutaneous coronary intervention (PCI) in patients on versus not on hemodialysis (HD) and examine whether high on-treatment platelet reactivity (HPR) further impacts outcomes among patients on HD., Background: Both chronic kidney disease (CKD) and HPR are predictors of major adverse cardiac events (MACE) after PCI., Methods: Two-year outcomes of patients from the prospective, multicenter ADAPT-DES study (N = 8,582) were analyzed according to HD status at enrollment. All patients underwent platelet function testing with the VerifyNow assay; HPR on clopidogrel was defined as P2Y12 reaction units (PRU) >208., Results: Compared with non-HD patients, patients on HD (n = 85) had significantly higher baseline PRU (median 254 vs. 188, p = .001) and more frequently had HPR (61.7% vs. 42.5%, p < .001). HD was associated with increased 2-year rates of MACE (death, myocardial infarction (MI) or definite stent thrombosis (ST); 23.4% vs. 10.7%, p < .001). HD was also strongly associated with 2-year overall mortality, cardiac death, MI, target vessel revascularization, major bleeding, stroke and ST. Following adjustment for HPR and other covariates, HD was independently associated with overall mortality, MI, ST, and major bleeding at 2 years. The relationship between HD status and 2-year MACE was consistent in patients with and without HPR (P interaction = .78)., Conclusions: Nearly two-thirds of patients on HD exhibited HPR on clopidogrel, and both HD and HPR were independently associated with 2-year adverse outcomes after DES implantation. However, the deleterious impact of HD on clinical outcomes was present in both patients with and without HPR., (© 2019 Wiley Periodicals, Inc.)

The global burden of atherothrombotic heart disease should be considered as a life-style disorder where differences in dietary habits and related risk factors like limited physical activity and adiposity together play important roles. Related metabolic changes have been scientifically elucidated in recent decades, and the role of the very-long-chain marine fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been much focused on, especially their possible effects on processes like inflammation and thrombosis. In the present brief review of related metabolic mechanisms, the effects of these fatty acids in a clinical setting have been referred to, including some of the authors' work on this topic. The main focus is the divergent results in the field and the important differences between the study population, the type of supplements and fresh marine sources, the proportion of EPA versus DHA dosages, and the duration of supplementation in clinical trials. We conclude that daily intake of at least 1 g of EPA + DHA may improve a dysmetabolic state in the population. The potential to reduce the risk and progression of atherothrombotic heart disease is still a matter of debate.

Aims: The dual antiplatelet therapy (DAPT) score is meant to aid clinicians choose the DAPT duration but attempts to examine the external validity of the DAPT score and its decision tool have reported mostly disappointing results. Our aim was to perform a meta-analysis of all available data on the external validity of the DAPT score., Methods and Results: We conducted a meta-analysis of studies that examined the external validity of the DAPT score/its decision tool. Seven studies (77 274 patients) were included. Follow-up ranged from 6 to 24 (median 18) months. Overall, high (≥2) DAPT score was associated with increased risk for myocardial infarction (MI)/stent thrombosis (ST) [odds ratio (OR) 1.54, 95% confidence interval (CI) 1.41-1.69; P < 0.01], and lower risk for bleeding (OR 0.84, 95% CI 0.73-0.97; P = 0.01). In the high DAPT score stratum, extended (12-24 months), as compared to standard (6-12 months) DAPT duration was associated with a reduction in the risk for MI/ST (OR 0.67, 95% CI 0.48-0.94; P = 0.02), and no difference in the risk for bleeding (OR 1.04, 95% CI 0.65-1.66; P = 0.88), while in the low DAPT score stratum, extended DAPT duration was associated with no difference in the risk for MI/ST (OR 1.04, 95% CI 0.76-1.43; P = 0.80), and an increased risk for bleeding (OR 1.58, 95% CI 1.15-2.15; P < 0.01)., Conclusions: This first meta-analysis of studies examining the external validation of the DAPT score and its decision tool, our results suggest that the DAPT score is useful both for stratifying post-percutaneous coronary intervention patients into risk strata for future ischaemic and bleeding events as well aiding in choosing the optimal DAPT duration for the individual patient., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Introduction/objectives: In patients who have undergone recent percutaneous coronary intervention (PCI), poor adhesion to antiplatelet agents may increase the risk of stent thrombosis and death. We aimed to investigate the adherence to different P2Y12 receptor inhibitors after PCI with drug-eluting stent in stable and unstable patients and to evaluate the factors associated with low adherence., Method: In a prospective study conducted between 2014 and 2018, the 8-item Morisky scale was applied at 30 days and 6 months post-PCI to measure P2Y12 receptor inhibitors adherence. Also, we describe the characteristics of patients using different platelet receptor P2Y12 inhibitors. Regression models were used to identify predictors of poor adherence., Results: A total of 214 patients were included (65 ± 12 years, 81% man, 61% acute coronary syndromes). Patients in the clopidogrel group were older than those in the prasugrel (68 ± 12 vs 59 ± 11 years, P < .01, respectively) or ticagrelor group (68 ± 12 vs 62 ± 12 years, P < .01). Patients with low/moderate adherence at 30 days and 6 months represented, respectively, 19.8% and 27.5% of our sample. Current smokers and preexisting cardiovascular disease at presentation were associated with lower adherence at 30 days., Conclusions: We found substantial rates of moderate and low adherence to P2Y12 receptor inhibitors early after PCI. Current smokers and preexisting cardiovascular disease at presentation were associated with a lower likelihood of adherence. These results highlight the need of monitoring adherence to medical treatment after PCI.

Background: There is a scarcity of data on short-duration dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy as compared with aspirin monotherapy after percutaneous coronary intervention (PCI)., Methods and results: STOPDAPT-1 is a prospective trial enrolling patients who agreed to 3-month DAPT followed by aspirin monotherapy after everolimus-eluting stent (EES) implantation. STOPDAPT-2 is a randomized trial comparing 1-month DAPT followed by clopidogrel monotherapy with 12-month DAPT after EES implantation. We compared the clinical outcomes of patients assigned to the 1-month DAPT group in STOPDAPT-2 and the 3-month DAPT group enrolled in STOPDAPT-1. The current study population consisted of 1,480 patients in STOPDAPT-2 and 1,339 patients in STOPDAPT-1. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, definite stent thrombosis and TIMI major/minor bleeding. Cumulative 1-year incidence of the primary endpoint was not significantly different between STOPDAPT-2 and STOPDAPT-1 (2.3% vs. 2.3%, P=0.98). After adjusting for confounders, there was no excess risk of STOPDAPT-2 relative to STOPDAPT-1 for the primary endpoint. Between 3 and 12 months, the cumulative incidence of primary endpoint was not significantly different between STOPDAPT-2 and STOPDAPT-1 (1.7% vs. 1.6%, P=0.77)., Conclusions: The effect of 1-month DAPT followed by clopidogrel monotherapy on clinical outcomes was similar to that of 3-month DAPT followed by aspirin monotherapy in patients receiving PCI.

Background: Stent thrombosis (ST) is a serious complication after drug-eluting stents (DES) implantation. To identify the risk factors of mortality following ST, we evaluated adverse event reports used for safety measures after approval., Methods and results: Between July 2004 and August 2019, 2,887 ST case reports were submitted to the Pharmaceutical and Medical Device Agency. Reports of probable or possible ST (n=604), with insufficient data regarding in-hospital outcome or duration between procedure and ST occurrence (n=37) or duplicate reports (n=191) were excluded. Accordingly, 2,045 reports with definite ST were analyzed. Among the subjects, there were 286 in-hospital deaths (14.0%). Multivariate logistic regression analysis revealed that left main trunk (LMT) (odds ratio [OR]: 4.76, 95% confidence interval [CI]: 3.26-6.96), chronic heart failure (CHF) (OR: 2.88, 95% CI: 1.61-5.14), hemodialysis (OR: 2.69, 95% CI: 1.66-4.36), prior stroke (OR: 2.28, 95% CI: 1.15-4.51), over 70 years old (OR: 1.62, 95% CI: 1.22-2.16), and right coronary artery (OR: 0.41, 95% CI: 0.27-0.63) were independent factors for in-hospital death after DES-ST., Conclusions: LMT, CHF, hemodialysis, prior stroke, and older age were independently associated with higher risk of in-hospital death following DES-ST. If target patients have these factors, maximum preventive strategies against ST occurrence, including adequate dual-antiplatelet therapy duration and optimal DES deployment procedures, are required.

Optimal timepoint for the discontinuation of dual antiplatelet therapy (DAPT) after an acute coronary syndrome is still debated. In fact, despite a shortening of DAPT duration should be advocated, based on the negligible risk of thrombotic complications observed with newer generations of drug-eluting stents (DES), in order to reduce the hemorrhagic risk, a more prolonged anti-ischemic protection would be suitable for certain higher-risk patients, rendering the traditional 12 months strategy outdated. We performed an updated meta-analysis and indirect comparison of randomized trials comparing shorter vs extended DAPT duration in ACS patients undergoing percutaneous coronary interventions with DES. Literature and main scientific session abstracts were searched for studies comparing 3-6 (short-term) or prolonged (> 12 months) DAPT vs traditional 12 months in ACS patients treated with DES. The primary efficacy endpoint was mortality, primary safety endpoint was the occurrence of major bleedings. Secondary endpoints were myocardial infarction and stent thrombosis. We included three randomized clinical trials and six study sub-analysis comparing alternative (short-term or prolonged) DAPT vs 12 months in post-ACS, with a total of 15,738 patients. Mortality occurred in 1.8% of patients, with no difference according to DAPT duration (short-term vs standard DAPT: OR [95% CI] 1.00 [0.72-1.39], p = 0.99; > 12 vs 12 months: OR [95% CI] 0.87 [0.61-1.22], p = 0.41). No difference in the risk of recurrent myocardial infarction and stent thrombosis was observed between short-term and standard DAPT, while a significant reduction was achieved only when extending the duration beyond 12 months (MI: OR [95% CI] 0.49 [0.36-0.67], p < 0.00001; ST: OR [95% CI] 0.40 [0.23-0.70], p = 0.001). However, prolonged DAPT was associated with a significant increase in major bleedings (OR [95% CI] 1.69 [1.17-2.45], p = 0.006). In fact, indirect comparison confirmed a significant interaction between short-term vs prolonged DAPT and the risk of myocardial infarction (p < 0.001), stent thrombosis (p = 0.0006) and major bleeding complications (p = 0.02). Based on the current meta-analysis, among ACS patients treated with percutaneous coronary interventions with DES, a shorter-term (3 or 6 months) DAPT can be safely considered, offering a non-inferior protection from major cardiovascular ischemic events as compared to the standard 12 months strategy. Extending DAPT therapy beyond 12 months enhances the antithrombotic protection, although paying the fee of increasing major bleeding complications, therefore resulting in a null effect on mortality.

Background: Prior randomized controlled trials (RCT) evaluating the optimal antithrombotic therapies for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) have not been powered to evaluate ischemic outcomes. We compared double therapy with oral anticoagulation (OAC) and a P2Y12 inhibitor to triple therapy with an OAC + dual antiplatelet therapy in patients with AF requiring PCI., Methods: Using PRISMA guidelines, we searched for RCTs including patients with AF as an indication for OAC and undergoing PCI or medical management of acute coronary syndrome. The results were pooled using fixed-effects and random-effects models to estimate the overall effect of double therapy versus triple therapy on ischemic and bleeding outcomes., Results: We identified four RCTs, comprising 10,238 patients (5,498 double therapy, 4,740 triple therapy). Trial-reported major adverse cardiovascular events were similar between double therapy and triple therapy (fixed effect model OR 1.09, 95% CI 0.94-1.26). However, stent thrombosis (61/5,496 double therapy vs. 33/4738 triple therapy; fixed effect model OR 1.57, 95% CI 1.02-2.40; number needed to treat with triple therapy = 242) favored triple therapy. Bleeding outcomes were less frequent with double therapy (746/5470 vs. 950/4710; fixed effect model OR 0.59, 95% CI 0.53-0.65; number needed to harm with triple therapy = 16), but with significant heterogeneity (Q = 8.33, p = .04; I 2 = 64%), as were intracranial hemorrhages (19/5470 vs. 30/4710; fixed effect model OR 0.54, 95% CI 0.31-0.96)., Conclusions: Double therapy in patients with AF requiring OAC following PCI or Acute coronary syndrome has a significantly better safety profile than triple therapy but may be associated with a modest increased risk of stent thrombosis., (© 2019 Wiley Periodicals, Inc.)

Purpose: Thrombosis within an occluded coronary arterial fistula (CAF) may cause angina and myocardial infarction. This study aims to estimate how the occlusion position of CAFs with terminal aneurysm affects the risk stratification of thrombosis in the fistula in terms of hemodynamics., Methods: Twelve CAF models were reconstructed based on patient-specific computed tomography angiogram (CTA) images. They were classified into three groups: preserved group (untreated fistula), aneurysm-reserved group (occluded at the fistula terminal: distal occlusion) and aneurysm-removed group (occluded before the aneurysm: proximal occlusion). Hemodynamics results were analyzed and compared with the clinical follow-up results., Results: The results showed that: (1) Hemodynamic patterns within the fistula before and after treatment were significantly different among patients. (2) Aneurysm-removed occlusions showed better improvements with respect to the CAF blood-stealing phenomena. (3) Irrespective of whether aneurysms were removed or not, a disturbed flow pattern was observed. Areas having high OSI and low TAWSS were present in the post-occluded CAFs. The removal of the aneurysm, however, would alleviate the flow disturbance, and decrease the proportion of the area of OSI > 0.3. (4) The thrombosis region spotted in the follow-up patient CTAs was consistent with the computed high OSI area., Conclusions: A proximal occlusion, namely, removing the aneurysm of the CAF, may help in reducing the risk of thrombosis after surgery. However, follow-up studies with a larger cohort should be carried out to test and verify this speculation in the future.

Diabetes mellitus (DM) is an independent predictor of adverse outcomes in patients with coronary artery disease (CAD). We investigated the interaction between DM and high platelet reactivity (HPR) in determining long-term clinical outcomes after percutaneous coronary intervention (PCI). We enrolled 500 patients who were divided based on the presence of DM and HPR. Primary endpoint was the occurrence of major adverse clinical events (MACE) at 5 years. Patients with both DM and HPR showed the highest estimates of MACE (37.9%, log-rank p < 0.001), all-cause death (15.5%, log-rank p = 0.022), and non-fatal myocardial infarction (25.9%, log-rank p < 0.001). At Cox proportional hazard analysis, the coexistence of DM and HPR was an independent predictor of MACE (HR 3.46, 95% CI 1.67-6.06, p < 0.001). Among patients with stable CAD undergoing elective PCI and treated with aspirin and clopidogrel, the combination of DM and HPR identifies a cohort of patients with the highest risk of MACE at 5 years.

Aims: Clopidogrel is prescribed for the prevention of atherothrombotic events. While investigations have identified genetic determinants of inter-individual variability in on-treatment platelet inhibition (e.g. CYP2C19*2), evidence that these variants have clinical utility to predict major adverse cardiovascular events (CVEs) remains controversial., Methods and Results: We assessed the impact of 31 candidate gene polymorphisms on adenosine diphosphate (ADP)-stimulated platelet reactivity in 3391 clopidogrel-treated coronary artery disease patients of the International Clopidogrel Pharmacogenomics Consortium (ICPC). The influence of these polymorphisms on CVEs was tested in 2134 ICPC patients (N = 129 events) in whom clinical event data were available. Several variants were associated with on-treatment ADP-stimulated platelet reactivity (CYP2C19*2, P = 8.8 × 10-54; CES1 G143E, P = 1.3 × 10-16; CYP2C19*17, P = 9.5 × 10-10; CYP2B6 1294 + 53 C > T, P = 3.0 × 10-4; CYP2B6 516 G > T, P = 1.0 × 10-3; CYP2C9*2, P = 1.2 × 10-3; and CYP2C9*3, P = 1.5 × 10-3). While no individual variant was associated with CVEs, generation of a pharmacogenomic polygenic response score (PgxRS) revealed that patients who carried a greater number of alleles that associated with increased on-treatment platelet reactivity were more likely to experience CVEs (β = 0.17, SE 0.06, P = 0.01) and cardiovascular-related death (β = 0.43, SE 0.16, P = 0.007). Patients who carried eight or more risk alleles were significantly more likely to experience CVEs [odds ratio (OR) = 1.78, 95% confidence interval (CI) 1.14-2.76, P = 0.01] and cardiovascular death (OR = 4.39, 95% CI 1.35-14.27, P = 0.01) compared to patients who carried six or fewer of these alleles., Conclusion: Several polymorphisms impact clopidogrel response and PgxRS is a predictor of cardiovascular outcomes. Additional investigations that identify novel determinants of clopidogrel response and validating polygenic models may facilitate future precision medicine strategies., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Purpose: Although current guidelines recommend the administration of dual antiplatelet therapy (DAPT) for up to 12 months after the implantation of a drug-eluting stent (DES), extended DAPT is frequently used in real-world practice., Materials and Methods: From the Korean Multicenter Angioplasty Team registry, we identified a total of 1414 patients who used DAPT for >3 years after DES implantation (extended-DAPT group) and conducted a landmark analysis at 36 months after the index procedure. We evaluated the determinants for and long-term outcomes of extended DAPT and compared the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE), defined as the composite of all-cause death, myocardial infarction, stent thrombosis, and stroke, between the extended-DAPT group and the guideline-DAPT group [DAPT <1 year after DES implantation (n=1273)]., Results: Multivariate analysis indicated the occurrence of acute coronary syndrome as the most significant clinical determinant of the use of extended DAPT. Bifurcation, stent diameter ≤3.0 mm, total stented length ≥28 mm, and use of first-generation DESs were also significant angiographic and procedural determinants. MACCE rates were similar between the extended-DAPT group and the guideline-DAPT group in crude analysis [hazard ratio (HR), 1.08; 95% confidence interval (CI), 0.69-1.68; p =0.739] and after propensity matching (HR, 1.22; 95% CI, 0.72-2.07; p =0.453). Major bleeding rates were comparable between the two groups., Conclusion: In patients undergoing percutaneous coronary intervention, indefinite use of DAPT does not show superior outcomes to those of guideline-DAPT. Major bleeding rates are also similar., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2020.)

Aims: In Japan, reduced-dose prasugrel (loading/maintenance dose, 20/3.75 mg) has been approved for use in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI), because of the higher bleeding risk among East Asians. However, its safety in the real-world population has not been investigated. We aimed to evaluate the effectiveness and safety of reduced-dose prasugrel vs. standard-dose clopidogrel in ACS patients undergoing PCI., Methods and Results: Acute coronary syndrome patients who underwent PCI in 2016, who were treated with either reduced-dose prasugrel or standard-dose clopidogrel in addition to aspirin, were identified from the nationwide Japanese PCI registry. The primary outcome was in-hospital mortality following PCI. Secondary outcomes included stent thrombosis and bleeding complication after PCI. Among 62 737 ACS patients who underwent PCI at any of 986 participating centres across Japan (clopidogrel 31.9%; prasugrel 68.1%), we identified 12 016 propensity score-matched pairs (24 032 patients; age 69.4 ± 12.2 years; female 24.9%; ST-elevation myocardial infarction 42.3%). Compared with standard-dose clopidogrel, reduced-dose prasugrel was associated with increased risk of bleeding [odds ratio (OR) 1.65, 95% confidence interval (CI) 1.10-2.51; P = 0.016], but both had similar rates of mortality (OR 1.11, 95% CI 0.89-1.38; P = 0.371) and stent thrombosis (OR 1.29, 95% CI 0.73-2.30; P = 0.387) as well as similar falsification endpoints of cardiac tamponade and emergent operation., Conclusion: In Japanese ACS patients undergoing PCI, the risk of bleeding is higher when using reduced-dose prasugrel than when using standard-dose clopidogrel, but there is no significant difference in in-hospital mortality and incidence of stent thrombosis between the two antiplatelet regimens., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: To mitigate the risk of stent thrombosis, patients treated by percutaneous coronary intervention (PCI) are administered dual anti-platelet therapy comprising aspirin and a platelet P2Y 12 receptor inhibitor. Clopidogrel is a prodrug requiring activation by the cytochrome P450 enzyme, CYP2C19. In Saudi Arabia, it has been reported that approximately 26% of the population carries CYP2C19*2 and/or *3 loss-of-function polymorphisms in addition to a high prevalence of CVD., Methods: This prospective (April 2013-December 2020) parallel assignment clinical trial focuses on ST-Elevation Myocardial Infarction (STEMI) patient outcomes. The clinical trial includes 1500 STEMI patients from two hospitals in the Eastern Province of Saudi Arabia. Patients are assigned to one of two groups; the control arm receives conventional therapy with clopidogrel, while in the active arm the Spartan RX CYP2C19 assay is used to determine the *2 genotype. Carriers of a CYP2C19*2 loss-of-function allele receive prasugrel or ticagrelor, while non-carriers are treated with clopidogrel. Follow-up is one year after primary PCI. The primary end point is the number of patients who develop an adverse major cardiovascular event, including recurrent MI, non-fatal stroke, cardiovascular death, or major bleeding one year after PCI., Discussion: The risk of stent thrombosis in PCI patients is usually reduced by dual anti-platelet therapy, comprising aspirin and a P2Y12 inhibitor, such as clopidogrel. However, clopidogrel requires activation by the cytochrome P450 enzyme, CYP2C19. Approximately 20% of the population are unable to activate clopidogrel as they possess the CYP2C19*2 loss-of function (LoF) allele. The primary goal of this trial is to study the benefits of treating only those patients that cannot activate clopidogrel with an alternative that has shown to be a more effective platelet inhibitor and does not require bioactivation by the cytochrome P450 enzyme. We expect an improvement in net clinical benefit outcome in the active arm patients, thus supporting pharmacogenetic testing in PCI patients post STEMI., Trial Registration: Trial registration name is "Bedside Testing of CYP2C19 Gene for Treatment of Patients with PCI with Antiplatelet Therapy" (number NCT01823185) retrospectively registered with clinicaltrials.gov on April 4, 2013. This trial is currently at the patient recruitment stage.

Warfarin treatment has been associated with lower risks of prostate cancer, without a specified biological mechanism. Our study tested the hypothesis that reluctance to perform prostate biopsies in men who are anticoagulated results in lower rates of diagnosed prostate cancer, leading to an apparent protective effect. Rates of prostate biopsies have decreased from 2000 to 2015, allowing calendar time to be used as the intervention. In a national population-based sample of elderly men, our study compared trends in prostate cancer incidence between 17,815 men treated with chronic oral anticoagulation for prosthetic heart valve thromboprophylaxis and a general population comparison group of 356,300 men. Cancer events were based on administrative claims. Among men enrolled in 2000-2001 and followed through 2015, prostate cancer incidence was substantially lower in the anticoagulation group (adjusted incidence rate ratio [IRR] 0.70; 95% confidence interval [CI] 0.62-0.80). Incidence decreased over time in the general population group to approach that of the anticoagulation group among men enrolled in 2008-2010 (IRR 0.86; 95% CI 0.71-1.04). Rates of prostate biopsies also decreased over time in the general population group to match the rate in the anticoagulation group. These results indicate that the apparent protective effect of warfarin treatment on the risk of prostate cancer is likely the result of detection bias from lower rates of biopsies among men who are anticoagulated., (© 2019 UICC.)

Kounis syndrome was recognized as the concurrence of acute cardiovascular events with hypersensitivity reactions. We report a case of Kounis syndrome type III (coronary thrombosis) variant in a 48-year-old man who had experienced recurrent acute myocardial infarctions after scallion-induced hypersensitivity reactions. After appropriate antithrombotic, antihistamine, and reperfusion strategies, the patient was found to have elevated levels of immunoglobulin E and chronic urticaria. Upon administration of omalizumab, there was an improvement of chronic urticaria, a decrease in immunoglobulin E levels, and resolution of the ischemic attacks., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Objectives: The objective of this post hoc analysis was to analyze real-world dual antiplatelet therapy (DAPT) regimens following polymer-free sirolimus-eluting stent (PF-SES) implantations in an unselected patient population., Methods: Patient-level data from two all-comers observational studies (ClinicalTrials.gov Identifiers: NCT02629575 and NCT02905214) were pooled and analyzed in terms of their primary endpoint. During the data verification process, we observed substantial deviations from DAPT guideline recommendations. To illuminate this gap between clinical practice and guideline recommendations, we conducted a post hoc analysis of DAPT regimens and clinical event rates for which we defined the net adverse event rate (NACE) consisting of target lesion revascularization (TLR, primary endpoint of all-comers observational studies) all-cause death, myocardial infarction (MI), stent thrombosis (ST), and bleeding events. A logistic regression was utilized to determine predictors why ticagrelor was used in stable coronary artery disease (CAD) patients instead of the guideline-recommended clopidogrel., Results: For stable CAD, the composite endpoint of clinical, bleeding, and stent thrombosis, i.e., NACE, between the clopidogrel and ticagrelor treatment groups was not different (5.4% vs. 5.1%, p = 0.745). Likewise, in the acute coronary syndrome (ACS) cohort, the NACE rates were not different between both DAPT strategies (9.2% vs. 9.3%, p = 0.927). There were also no differences in the accumulated rates for TLR, myocardial infarction ([MI], mortality, bleeding events, and stent thrombosis in elective and ACS patients. The main predictors for ticagrelor use in stable CAD patients were age < 65 years, smaller vessels, treatment of ostial and calcified lesions, and in-stent restenosis., Conclusion: Within the framework of a post hoc analysis based on a real-world, large cohort study, there were no differences in the combined endpoint of major adverse cardiac events (MACE), bleeding and thrombotic events for clopidogrel and ticagrelor in stable CAD or ACS patients. Despite the recommendation for clopidogrel by the European Society of Cardiology (ESC), real-world ticagrelor use was observed in subgroups of stable CAD patients that ought to be explored in future trials.

Aims: To report procedural and 1-year outcomes following COBRA PzF NCS implantation in a routine daily setting with high bleeding risk (HBR) patients treated with clopidogrel as mono antiplatelet therapy (MAPT)., Methods: This is a prospective, consecutive, observational study in HBR patients who underwent PCI with COBRA PzF NCS and treated with clopidogrel alone at discharge. The primary endpoint was definite stent thrombosis at one month. The secondary endpoint was MACE (Cardiac Death, myocardial infarction (MI), target lesion revascularization (TLR)) at 12 months., Results: From October 2015 to December 2018, 77 patients with 120 lesions were enrolled and treated. Mean age was 78.7 ± 8.89 years, 58.5% men and 18.2% had ACS. Patients included had a minimum of 2.0 inclusion LEADERS FREE criteria. Angiographic success was achieved in all cases. The primary endpoint occurred in 0%, no stent thrombosis was occurred. MACE at 12-months (available for 52 patients) was 3.8% including cardiac death 0%, MI 0% and TLR 3.8%. No severe bleeding events (BARC3-5) or stroke or late stent thrombosis were noted., Conclusion: Clopidogrel as MAPT after COBRA PzF NCS implantation in HBR patients is feasible and an attractive option. One-year follow-up was associated with excellent clinical outcomes and should be confirmed with large randomised study., Condensed Abstract: This is prospective registry of high bleeding risk patients treated with the COBRA PzF NCS and MAPT at discharge. The primary end point demonstrated no stent thrombosis. The rate of major cardiac adverse events (a composite of cardiovascular death, myocardial infarction and target lesion revascularisation) at 1 year was 3.8%. No severe bleeding events, stroke or late stent thrombosis were noted. One-year follow-up was associated with good clinical outcomes and compared favorably with current devices., Competing Interests: Declaration of competing interest LM is consultant for CeloNova BioSciences, Inc. (modest). The other authors have no disclosure., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Even among biomarker-negative patients undergoing elective percutaneous coronary intervention (PCI), periprocedural thrombotic and bleeding complications can lead to increased morbidity and mortality. Whether stronger platelet inhibition by an intensified oral loading strategy (ILS) before PCI impacts on outcomes among these patients in contemporary practice remains unclear., Methods: This multicenter, randomized, assessor-blinded trial tested the hypothesis that in elective PCI prasugrel 60 mg (ILS) is superior to standard loading strategy with clopidogrel 600 mg regarding a composite primary end point of all-cause death, any myocardial infarction, definite/probable stent thrombosis, stroke, or urgent vessel revascularization. After PCI, all patients were on clopidogrel 75 mg/day and aspirin. The trial was terminated prematurely because of slower-than-expected recruitment and funding discontinuation., Results: Of 781 patients included in the final analysis, 382 were assigned to ILS and 399 to standard loading strategy. At 30 days, the primary end point occurred in 66 patients (17.3%) assigned to ILS and 74 patients (18.6%) assigned to standard loading strategy (odds ratio, 0.92 [95% CI, 0.63-1.32]; P =0.64). Any myocardial infarction and Bleeding Academic Research Consortium ≥2 bleeding rates were similar among ILS and standard loading strategy groups 16.2% versus 17.5%, odds ratio, 0.91 (95% CI, 0.62-1.32), P =0.62 and 4.2% versus 4.8%, odds ratio 0.87 (95% CI, 0.44-1.73), P =0.70, respectively., Conclusions: In biomarker-negative stable and unstable angina patients undergoing elective PCI, the trial did not find a conclusive difference in efficacy or safety. This observation should be interpreted in the context of wide CIs and premature termination of the trial. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02548611.

Background: In AUGUSTUS (Open-Label, 2×2 Factorial, Randomized, Controlled Clinical Trial to Evaluate the Safety of Apixaban vs Vitamin K Antagonist and Aspirin vs Aspirin Placebo in Patients With Atrial Fibrillation and Acute Coronary Syndrome and/or Percutaneous Coronary Intervention), patients with atrial fibrillation and a recent acute coronary syndrome and those undergoing percutaneous coronary intervention had less bleeding with apixaban than vitamin K antagonist (VKA) and with placebo than aspirin. However, the number of ischemic events was numerically higher with placebo. The aim of this analysis is to assess the tradeoff of risk (bleeding) and benefit (ischemic events) over time with apixaban versus VKA and aspirin versus placebo., Methods: In AUGUSTUS, 4614 patients with atrial fibrillation and recent acute coronary syndrome or percutaneous coronary intervention on a P2Y 12 inhibitor were randomized to blinded aspirin or placebo and to open-label apixaban or VKA for 6 months. In a post hoc analysis, we compared the risk of 3 composite bleeding outcomes and 3 composite ischemic outcomes from randomization through 30 days and from 30 days to 6 months with apixaban and VKA and with aspirin and placebo., Results: Compared with VKA, apixaban had either a lower or a similar risk of bleeding and ischemic outcomes from randomization to 30 days and from 30 days to 6 months. From randomization to 30 days, aspirin caused more severe bleeding (absolute risk difference, 0.97% [95% CI, 0.23-1.70]) and fewer severe ischemic events (absolute risk difference, -0.91% [95% CI, -1.74 to -0.08]) than placebo. From 30 days to 6 months, the risk of severe bleeding was higher with aspirin than placebo (absolute risk difference, 1.25% [95% CI, 0.23-2.27]), whereas the risk of severe ischemic events was similar (absolute risk difference, -0.17% [95% CI, -1.33 to 0.98])., Conclusions: In patients with atrial fibrillation and recent acute coronary syndrome or percutaneous coronary intervention receiving a P2Y 12 inhibitor, apixaban is preferred over VKA. Use of aspirin immediately and for up to 30 days results in an equal tradeoff between an increase in severe bleeding and a reduction in severe ischemic events. After 30 days, aspirin continues to increase bleeding without significantly reducing ischemic events. These results inform shared, patient-centric decision making on the ideal duration of the use of aspirin after an acute coronary syndrome or percutaneous coronary intervention in patients with atrial fibrillation receiving oral anticoagulation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02415400.

Background: Stent thrombosis (ST) is a dreaded complication after stent implantation and is associated with a mortality between 5% and 45%. The mechanisms by which ST arises are complex. Because of the seriousness of this situation, all phy - sicians should have at least basic knowledge of it. In this article, we present the risk factors for ST and discuss some innovative approaches to its treatment., Methods: This review is based on pertinent articles retrieved by a selective search in PubMed, and on current international guidelines and expert recommendations., Results: The frequency of ST has been markedly lowered by technical advances in coronary stenting and by the implementation of modern implantation techniques, including the introduction of coverage with dual antiplatelet therapy (DAPT). Both patient-related risk factors and procedural aspects can elevate the risk of ST. The independent risk factors for ST include premature termination of DAPT (hazard ratio [HR] 26.8; 95% confidence interval [8.4; 85.4]; p <0.0001), malignant disease (odds ratio [OR]: 17.45; [4.67; 65.26]; p <0.0001), and diabetes mellitus (OR: 3.14; [1.33; 7.45]; p = 0.0093). In comparison to angiographically guided procedures, the use of intracoronary imaging techniques in patients with acute coronary syndrome lowers the frequency of ST (0.6% versus 1.2%; p = 0.005). These techniques enable the detection of many findings in the coronary arteries that are associated with the development of ST. In such cases, countermeasures such as secondary stent dilatation or prolongation of DAPT can help prevent ST., Conclusion: As the pathophysiology of ST is multifactorial, research in this area presents a special challenge. Prospective clinical trials will be needed to determine whether the systematic use of imaging techniques can lower the frequency of ST.