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BackgroundTriple antithrombotic therapy (TAT), a combination of an oral anticoagulant and dual antiplatelet therapy (DAPT), is a key treatment for prevention of ischemic events in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). However, TAT is not extensively used because of the risk of bleeding. This study aimed to determine the utilization and influencing factors of TAT using real-world data in the non-vitamin K antagonist oral anticoagulants (NOACs) era.MethodsWe analyzed National Inpatient Sample data compiled by the Health Insurance Review & Assessment Service (HIRA-NIS) from 2011 to 2020. Patients with AF who underwent PCI with stent implantation and with an increased stroke risk were selected as candidates for TAT therapy. Demographic and clinical factors associated with TAT use were investigated using the chi-squared test and the Student t-test, and influencing factors were identified using multiple logistic regression.ResultsThe TAT utilization rate steadily increased from 30.3% in 2011 to 65.4% in 2020 (Cochran-Armitage trend test: p < 0.001) with an average of 45.9%. Positive influencing factors for TAT use were identified as congestive heart failure, history of previous stroke/transient ischemic attack/thromboembolism, valvular heart disease, and year. Negative influencing factors included insurance type (medical aid or Patriots & Veterans Insurance), type of medical institution (general hospitals or primary medical institutions), and comorbidities such as renal disease, liver disease, and history of the previous hemorrhage.ConclusionsThe utilization of TAT following PCI among high-stroke risk AF patients steadily increased from 2011 to 2020, reaching 65.4% by the end of the study period. However, in 2020, a significant proportion of 29.4% of patients still received DAPT, indicating that many AF patients undergoing PCI did not receive adequate antithrombotic therapy.

Over the past two decades, the combined use of long-term anticoagulation and antiplatelet therapy following percutaneous coronary intervention has been extensively investigated. Efforts to define an optimal antithrombotic strategy-balancing protection against thrombotic and thromboembolic events with minimization of bleeding risk-have led to the design and conduct of randomized clinical trials. This narrative review synthesizes the main evidence comparing different antithrombotic approaches in this setting, with particular focus on regimens stratified by oral anticoagulant type and on the direct comparison between aspirin- and clopidogrel-based double antithrombotic therapy, as evaluated in a limited number of recent studies. Further large-scale randomized data comparing these two regimens are needed to strengthen the current evidence and clarify this issue, as well as to evaluate the role of platelet function and/or genetic testing in guiding the selection of the optimal antiplatelet agent.

PurposeOutcomes from randomized controlled trials (RCTs) inform the latest recommendations on percutaneous coronary intervention (PCI) management of a short period of oral anticoagulation (OAC), a P2Y12 receptor inhibitor, and aspirin for 1 week or until hospital discharge in patients with atrial fibrillation (AF) undergoing PCI, and up to 4 weeks in individuals considered to be at high-risk for ischemic events, followed by discontinuation of aspirin and continuation of OAC and a P2Y12 inhibitor for up to 12 months.MethodsWe examined and summarized the outcomes of bleeding and major adverse cardiac events (MACEs) from RCTs and meta-analyses, published between 2013 and 2022, comparing therapy with OAC and a P2Y12 inhibitor with and without aspirin in AF patients undergoing PCI with stenting.ResultsData comparing dual therapy with OAC and a P2Y12 inhibitor alone to triple therapy with OAC, a P2Y12 inhibitor, and aspirin with respect to the risks of MACEs, including stent thrombosis within the first 30 days, are underpowered and inconclusive. The addition of aspirin does not appear to be associated with a decreased risk of ischemic events, even in patients with high-risk CHA2DS2-VASc scores, but does significantly increase bleeding hazards. The increased safety of newer generation drug-eluting stents may have further minimized any theoretical anti-ischemic benefits of aspirin. The possible attenuation of the pleiotropic effects of concomitant cardiovascular medications by aspirin may also have been a contributing factor.ConclusionThe addition of aspirin to OAC and a P2Y12 inhibitor is likely associated with a net clinical harm in patients with AF who undergo PCI with stenting, even within the first 1–4 weeks after PCI. Revisiting the guideline recommendations to administer aspirin in this timeframe may be warranted.

Acute coronary syndrome (ACS) is one of the leading causes of death worldwide. Percutaneous coronary intervention (PCI) is the treatment of choice for ACS as this procedure reduces the morbidity and mortality rates of patients in clinical trials and daily practice. However, patients with a history of prior ACS who undergo PCI are still at high risk for recurrent major adverse cardiac events (MACE). Because the antithrombotic drugs reduce the rate of MACE and minimize stent-related complications such as target vessel failure or stent thrombosis, the utilization of these agents is the cornerstone treatment for secondary prevention of ACS patients after PCI. Unfortunately, using the antithrombotic agents may be associated with bleeding complications, including major or fatal bleeding. Therefore, premature discontinuation of antithrombotic regimens regarding the hemorrhagic events is sometimes inevitable and possibly leads to fatal complications such as stent thrombosis. To minimize the bleeding issues, shorten antithrombotic regimens have been proposed, which theoretically offers improved safety. Nevertheless, inappropriate withdrawal of antithrombotic drugs may increase the rate of ischemic events. On the other hand, an unnecessary prolonged antithrombotic regimen may cause avoidable bleeding. Balancing the risk of bleeding against the benefits of using antithrombotic drugs is therefore challenging especially for the patients who contain both bleeding and ischemic risks such as ACS patients who are concomitant using the anticoagulants. Currently, the treatment paradigms are shifting from the \"one size fits all approach\" toward the \"tailored approach\". This means that the antithrombotic regimens can be adjustable individually. As a result, various clinical risk scoring systems have been established to help physicians with their decision-making. However, besides the development of these dedicated scoring tools, clinical judgment for balancing the safety versus the efficacy before deciding on the antithrombotic plan is still imperative.

Abstract Aims The efficacy and safety of ticagrelor or prasugrel vs. clopidogrel in patients with atrial fibrillation (AF) on oral anticoagulation (OAC) undergoing percutaneous coronary intervention (PCI) for myocardial infarction (MI) have not been established. Methods and results This was a nationwide cohort study of patients on OAC for AF who underwent PCI for MI from 2011 through 2019 and were prescribed a P2Y12 inhibitor at discharge. The primary efficacy outcome was major adverse cardiovascular events (MACE), defined as a composite of death from any cause, stroke, recurrent MI, or repeat revascularization. The primary safety outcome was cerebral, gastrointestinal, or urogenital bleeding requiring hospitalization. Absolute and relative risks for outcomes at 1 year were calculated through multivariable logistic regression with average treatment effect modelling. Outcomes were standardized for the individual components of the CHA2DS2-VASc and HAS-BLED scores as well as type of OAC, aspirin, and proton pump inhibitor use. We included 2259 patients of whom 1918 (84.9%) were prescribed clopidogrel and 341 (15.1%) ticagrelor or prasugrel. The standardized risk of MACE was significantly lower in the ticagrelor or prasugrel group compared with the clopidogrel group (standardized absolute risk, 16.3% vs. 19.4%; relative risk, 0.84, 95% confidence interval, 0.70–0.98; P = 0.02), while the risk of bleeding did not differ (standardized absolute risk, 5.5% vs. 5.1%; relative risk, 1.07, 95% confidence interval, 0.73–1.41; P = 0.69). Conclusion In patients with AF on OAC who underwent PCI for MI, treatment with ticagrelor or prasugrel vs. clopidogrel was associated with reduced ischaemic risk, without a concomitantly increased bleeding risk. Graphical Abstract Graphical abstract

Patients with atrial fibrillation (AF) are at increased risk for coronary artery disease (CAD). After percutaneous coronary intervention (PCI), the antithrombotic therapy consists of a combination of anticoagulant and antiplatelet agents to reduce the ischemic and thromboembolic risk, at the cost of increased bleeding events. In the past few years, several randomized clinical trials involving over 12,000 patients have been conducted to compare the safety of vitamin K antagonist (VKA) and direct-acting oral anticoagulants (DOACs) in association with a single- or double-antiplatelet agent, in the so-called dual- (DAT) or triple-antithrombotic therapy (TAT). These studies and several meta-analyses showed a consistent benefit for reducing bleeding events of DAT over TAT and of DOAC over VKA, without concerns about ischemic endpoints, except for a trend for increased stent thrombosis risk. The present paper examines current international guidelines’ recommendations and reviews clinical trials, meta-analyses, and observational studies conducted on AF patients treated with DAT or TAT after PCI for acute coronary syndromes.

Up to 10% of patients with atrial fibrillation (AF) undergo percutaneous coronary intervention (PCI). A systematic review and network meta-analysis were conducted by searching PubMed, Embase, and the Cochrane database of systematic reviews for randomized control trials that studied the safety and efficacy of different antithrombotic strategies in these patients. Six studies, including 12,158 patients were included. Compared to that in the triple antithrombotic therapy group (vitamin K antagonist (VKA) plus P2Y12 inhibitor and aspirin), thrombolysis in myocardial infarction (TIMI) major bleeding was significantly reduced in the dual antithrombotic therapy (non-vitamin K oral anticoagulants (NOACs) plus P2Y12 inhibitor) group by 47% (Odds ratio (OR), 0.53; 95% credible interval [CrI], 0.35–0.78; I2 = 0%). Besides, NOAC plus a P2Y12 inhibitor was associated with less intracranial hemorrhage compared to VKA plus single antiplatelet therapy (OR: 0.20, 95% CrI: 0.05–0.77). There was no significant difference in the trial-defined major adverse cardiac events or the individual outcomes of all-cause mortality, cardiovascular death, myocardial infarction, stroke or stent thrombosis among all antithrombotic strategies. In conclusion, antithrombotic strategy of NOACs plus P2Y12 inhibitor is safer than, and as effective as, the strategies including aspirin when used in AF patients undergoing PCI.

Background： It is currently believed that triple oral antithrombotic therapy in patients with atrial fibrillation （AF） after percutaneous coronary intervention （PCI） should be recommended if there are no contraindications. However, selecting triple therapy for AF patients undergoing PCI is still challenging when bleeding risk is considered. This study aimed to investigate the current use of oral anticoagulants （Vitamin K antagonists [VKA]） and perform prognostic analysis in real-world patients with AF undergoing coronary stenting. Methods： A total of 276 consecutive coronary artery disease （CAD） patients with or without AF undergoing coronary stenting were retrospectively evaluated and analyzed. The univariate and multivariate analyses were conducted to explore the current use of VKA and prognosis of patients with AF undergoing coronary stenting. The primary end-point was composite of all-cause death, nonfatal recurrent myocardial infarction, stroke, serious bleeding events, unplanned repeat revascularization, and worsening heart failure at 12-month follow-up after coronary stenting. Results： AF patients undergoing coronary stenting have more clinical concomitant diseases. Only 9.0% AF patients after coronary stenting received triple antithrombotic therapy （VKA, aspirin, and clopidogrel） at discharge. AF was independently associated with increased risk of the 12-month composite end-points （relative risk = 5.732, 95% confidence interval 1.786-18.396, P = 0.003）. Conclusions： In real-life AF patients undergoing coronary stenting, guideline-recommended VKA was less used. AF patients had adjusted worse prognosis during 12-month follow-up after discharge. It is of utmost importance to improve the current status of oral anticoagulants use.

In a randomized trial involving patients who had a first stroke from an embolus of unknown source, rivaroxaban at a daily dose of 15 mg did not result in a lower incidence of recurrent stroke than aspirin at a dose of 100 mg. Bleeding rates were higher with rivaroxaban.

The world continues to contend with COVID-19, fueled by the emergence of viral variants. At the same time, a subset of convalescent individuals continues to experience persistent and prolonged sequelae, known as long COVID. Clinical, autopsy, animal and in vitro studies all reveal endothelial injury in acute COVID-19 and convalescent patients. Endothelial dysfunction is now recognized as a central factor in COVID-19 progression and long COVID development. Different organs contain different types of endothelia, each with specific features, forming different endothelial barriers and executing different physiological functions. Endothelial injury results in contraction of cell margins (increased permeability), shedding of glycocalyx, extension of phosphatidylserine-rich filopods, and barrier damage. During acute SARS-CoV-2 infection, damaged endothelial cells promote diffuse microthrombi and destroy the endothelial (including blood–air, blood–brain, glomerular filtration and intestinal–blood) barriers, leading to multiple organ dysfunction. During the convalescence period, a subset of patients is unable to fully recover due to persistent endothelial dysfunction, contributing to long COVID. There is still an important knowledge gap between endothelial barrier damage in different organs and COVID-19 sequelae. In this article, we mainly focus on these endothelial barriers and their contribution to long COVID.