Dual antithrombotic therapy (DAT) without aspirin reduces bleeding compared with triple antithrombotic therapy (TAT) in patients with atrial fibrillation who have undergone percutaneous coronary intervention, without apparently increasing ischemic events. A prospective pharmacodynamic study was performed to investigate the impact of aspirin on bleeding time, platelet function and fibrin clot analysis in this population. Patients receiving TAT (n = 16), comprising aspirin, ticagrelor/prasugrel and a direct-acting oral anticoagulant (DOAC), were compared with those receiving DAT without aspirin (n = 18). Bleeding time was reduced with DAT compared with TAT (median 27.8 vs 30.0 minutes, p = .005). Assessed by light transmission aggregometry, median platelet aggregation was significantly increased with DAT compared with TAT in response to arachidonic acid (63 vs 3%, p = .002) and collagen (72 vs 37%, p < .001) but not 5-μmol/L adenosine diphosphate (25 vs 27%, p = .966) or thrombin-receptor-activating peptide (37 vs 24%, p = .086). VerifyNow P2Y12 assay showed > 70% inhibition in all patients. Fibrin clot lysis time and maximum turbidity were similar between groups. Using P2Y12 inhibitors of consistent potency, DAT improves hemostasis through sparing cyclooxygenase-1-mediated platelet activation but has a comparable effect to TAT on other pathways and fibrin clot properties. DAT with ticagrelor/prasugrel and DOAC may provide sufficient antithrombotic effect without excessive anti-hemostatic effect.

Acute coronary syndrome (ACS) encompasses a spectrum of cardiovascular emergencies, including unstable angina and myocardial infarction, that require immediate and effective management to reduce morbidity and mortality. Antithrombotic therapy, including antiplatelet and anticoagulant medications, is fundamental in ACS management. We sought to organize the current status of antithrombotic management of ACS, including the concept of high bleeding risk (HBR), in line with the clinical diagnostic flow. ACS is an ever-changing condition; therefore, its diagnosis and treatment are conducted in parallel. While primarily a coronary artery disease, the diagnosis of ACS also includes conditions such as myocardial infarction with nonobstructive coronary arteries as a working diagnosis. This review collates the mechanisms and classification of ACS, showing the diagnostic flow and the antithrombotic agents used at each stage. It discusses strategies for dual antiplatelet therapy (DAPT) duration and de-escalation in patients undergoing percutaneous coronary intervention and addresses the management of patients requiring oral anticoagulation alongside antiplatelet therapy, highlighting the shift toward dual therapy to reduce bleeding risk. Antithrombotic agents are key treatments for ACS, with various available options. Their mechanisms and the approved dosing regimens differ regionally, especially between Japan and other countries. This review synthesizes the regional availability of each agent and compares the latest recommendations from Japanese and international guidelines for ACS management. The field of antithrombotic therapy in ACS is dynamic, influenced by the findings of ongoing clinical trials and emerging evidence. Key considerations include balancing antithrombotic benefits against bleeding risks, particularly in patients with HBR. Recent studies have explored shorter DAPT durations and novel antithrombotic agents, offering new insights for diverse patient populations. In this review, we provide a comprehensive comparison of guidelines and insights from the neuro-interventional field to assist clinicians in making informed decisions regarding ACS management. As ACS management evolves, continued international, cross-sectional collaboration and research are essential to refine guidelines and improve clinical practice.

Residual thrombosis risk is an important contributor to ischaemic events in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Although previous studies have shown that rivaroxaban 2.5 mg two times per day in ACS patients with high ischaemic risk can significantly reduce the risk of ischaemic recurrence and mortality, individualised treatment with low-dose rivaroxaban is still rare. Using D-dimer and PARIS (Patterns of non-Adherence to Anti-Platelet Regimen in Stented Patients) coronary thrombosis risk score to identify ACS patients at high ischaemic risk, we aim to investigate whether 3-month low-dose rivaroxaban therapy on the basis of dual antiplatelet therapy (DAPT) could result in reduced ischaemic events without increasing bleeding.

This study is a multicentre, prospective, open-label, randomised controlled trial involving 3944 ACS patients undergoing PCI from more than 40 tertiary hospitals in China (ClinicalTrials.gov NCT05638867). Patients with PARIS coronary thrombosis score ≥3 or D-dimer ≥0.28 µg/mL will be 1:1 randomised to the experimental group (rivaroxaban 2.5 mg two times per day for 3 months on the basis of 1 year standard DAPT) or the control group (1 year standard DAPT only). The primary endpoint of this study is major adverse cardiovascular and cerebrovascular events (MACCE), a composite of death, myocardial infarction, unplanned ischaemia-driven revascularisation and systemic embolic events. The safety endpoint is Bleeding Academic Research Consortium (BARC) type 3 and 5 bleeding events.

Institutional Review Board (IRB) approval by the Ethics Committee of Fuwai Hospital was obtained on 22 April 2023 (Approval No. 2023-1980). The investigators will have access to the final dataset. Trial results will be made public through publication in professional journals.

NCT05638867.

Bleeding complications are a significant concern in the management of acute coronary syndromes (ACS). The evidence from clinical trials demonstrates the need for balancing efficacy in reducing ischemic events with safety concerns, as bleeding events adversely affect prognosis and mortality. Pharmacological agents like aspirin, P2Y12 inhibitors (e.g., prasugrel, ticagrelor), glycoprotein IIb/IIIa inhibitors, and heparins are fundamental to ACS treatment but carry varying bleeding risks depending on individual patient profile. Recent advancements in risk stratification tools have enabled tailored approaches to dual antiplatelet therapy (DAPT), optimizing its duration based on bleeding and thrombotic risks. Further Emerging therapies, including shortened DAPT protocols and P2Y12 inhibitor monotherapy, have shown promise in minimizing bleeding while maintaining clinical efficacy. The findings underscore the importance of personalized antithrombotic regimens in ACS management, emphasizing precise risk assessment to enhance outcomes and mitigate adverse events. This review examines the mechanisms, risk factors, and strategies to mitigate bleeding associated with anticoagulant and antiplatelet therapies in ACS.

BackgroundPatients with atrial fibrillation often require anticoagulation therapy to prevent stroke and thromboembolism. However, anticoagulants can have serious side effects, such as bleeding, particularly when combined with antiplatelet therapy.ObjectiveThe aim of this study is to estimate the prevalence of major bleeding in patients receiving either dual or triple antithrombotic therapy.MethodThis study is a single-center retrospective chart review utilizing the hospital electronic health record. The prevalence and percentage of bleeding events were reported for each antithrombotic regimen.ResultsOf the 539 patients receiving oral anticoagulants, 202 were using oral anticoagulants in combination with either single or dual antiplatelet therapy. Out of 35 patients using triple antithrombotic therapy, four (11.4%) experienced major bleeding. Based on the analysis of 73 patients using anticoagulants in combined with clopidogrel, the results showed that one patient (1.3%) suffered bleeding. Among the 94 patients treated with anticoagulants plus aspirin, seven (7.4%) experienced major bleeding events.ConclusionThe combination of anticoagulants and antiplatelet agents is associated with an elevated bleeding risk. Patients receiving triple antithrombotic therapy experience high prevalence of bleeding. Nonetheless, the group receiving anticoagulant and clopidogrel alone exhibited low prevalence of bleeding risk.

Dual antiplatelet therapy with P2Y12 inhibitors (P2Y12i) and aspirin following acute myocardial infarction (AMI) prevents future ischaemic events. People with atrial fibrillation (AF) also require oral anticoagulants (OAC), increasing bleeding risk. Guidelines recommend post-discharge prescribing of direct OAC with clopidogrel and discontinuation of P2Y12i after 12 months, but little is known about use in clinical practice.

To describe post-discharge use of OACs and P2Y12i in people with AF and a history of OAC use hospitalized for AMI.

We identified 1330 people hospitalized for AMI with a diagnosis of AF and history of OAC use in New South Wales, Australia, July 2018-June 2020. We identified three aspects of post-discharge antithrombotic medicine use with possible safety implications: (1) not being dispensed OACs; (2) dispensing OAC and P2Y12i combinations associated with increased bleeding (involving warfarin, ticagrelor, or prasugrel); and (3) P2Y12i use longer than 12 months.After discharge, 74.3% of people were dispensed an OAC, 45.4% were dispensed a P2Y12i, and 35.8% were dispensed both. People with comorbid heart failure or cancer were less likely to receive OACs. Only 11.2% of people who dispensed both an OAC and P2Y12i received combinations associated with increased bleeding; this was more common among people with chronic kidney disease or prior warfarin or statin use. A total of 44.6% of people dispensed both medicines continued P2Y12i for over 12 months; this was more common in people who received a revascularization or lived in areas of social disadvantage.

We identified potential gaps in pharmacotherapy, including underuse of recommended therapies at discharge, use of combinations associated with increased bleeding, and P2Y12i use beyond 12 months. Prescribing vigilance across both hospital and community care is required.

In the past decades, percutaneous coronary intervention (PCI) has become the most common modality for myocardial revascularization in patients with coronary artery disease (CAD). Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is essential in all patients undergoing PCI to prevent thrombotic complications. A large proportion of patients undergoing PCI also have concomitant atrial fibrillation (AF), thus requiring an oral anticoagulant (OAC) to prevent ischemic stroke or systemic embolism. However, the association between OAC and DAPT further increases the risk of bleeding. Compared with a triple antithrombotic therapy (TAT), dual antithrombotic therapy (DAT) has shown to reduce bleeding events, but at the cost of higher risk of stent thrombosis. In this field, patients with AF undergoing PCI represent a special population with significant challenges, and several strategies are needed to reduce the risk for bleeding complications. In this review, we will discuss both the procedural and antithrombotic strategies to optimize ischemic and bleeding outcomes in patients with AF undergoing PCI.

The optimal antithrombotic therapy strategies for patients with atrial fibrillation (AF) and acute myocardial infarction (AMI) remain uncertain. We aimed to evaluate the efficacy and safety of oral anticoagulants (OAC) among patients with AF and AMI.

PubMed, Embase, and Web of Science were searched from inception till 5 February 2025. The primary outcome was any stroke.

Eleven studies with 83 549 patients were included. OAC therapy was associated with lower risks of any stroke (odds ratio [OR]: 0.68; 95% confidence interval [CI]: 0.60-0.77; P < .001), ischemic stroke (OR: 0.64; 95% CI: 0.57-0.73; P < .001), and all-cause mortality (OR: 0.81; 95% CI: 0.74-0.89; P < .001). Additionally, OAC therapy was associated with a higher risk of any bleeding (OR: 1.24; 95% CI: 1.06-1.46; P = .009), but not for major bleeding (OR: 1.28; 95% CI: 0.87-1.90; P = .21).

OAC therapy is effective for patients with AF and AMI, but should be administered cautiously in those at high bleeding risk.

The "2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes" incorporates new evidence since the "2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction" and the corresponding "2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes" and the "2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction." The "2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes" and the "2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization" retire and replace, respectively, the "2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease."

A comprehensive literature search was conducted from July 2023 to April 2024. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.

Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

Acute coronary syndrome (ACS) and stroke are interconnected conditions that often share risk factors such as atherosclerosis, thrombosis, and systemic inflammation. When these events occur simultaneously, they present unique diagnostic and therapeutic challenges. This review explores the pathophysiological mechanisms linking ACS and stroke, including common pathways like plaque instability, cardioembolism, and endothelial dysfunction, while highlighting the distinct features of ischemic and hemorrhagic strokes. The manuscript provides an overview of diagnostic strategies, emphasizing the role of biomarkers, advanced neuroimaging, and risk stratification tools in guiding acute management. Furthermore, the review delves into treatment approach, emphasizing the need to balance reperfusion therapies for ACS with thrombolysis or thrombectomy for ischemic stroke while carefully managing the challenges posed by anticoagulation in cases complicated by bleeding. Long-term strategies for secondary prevention are examined, including antithrombotic regimens tailored to the dual risk of thrombosis and bleeding, as well as lipid-lowering and blood pressure management. Future perspectives highlight the potential of novel pharmacological agents, neuroprotective therapies, and AI-driven tools to enhance patient outcomes. This review underscores the importance of integrated, multidisciplinary care and identifies key areas for future research to optimize the management of these high-risk patients.

Dual antiplatelet therapy (DAPT) is the cornerstone for patients with coronary atherosclerotic heart disease (CHD) undergoing percutaneous coronary intervention (PCI) while increasing the risk of bleeding, particularly when combined with gastrointestinal disease (GID). Rivaroxaban 10 mg once daily is widely used in Asia. This study compared the effects of low-dose rivaroxaban (10 mg daily) plus clopidogrel vs. DAPT in CHD patients with GID undergoing PCI.

In this prospective, single-center, randomized controlled trial, eligible CHD patients with GID undergoing PCI were randomized (1:1) to either the dual pathway inhibition (DPI) group (rivaroxaban 10 mg plus clopidogrel 75 mg daily) or the DAPT group (aspirin 100 mg plus clopidogrel 75 mg daily). The primary outcome was Bleeding Academic Research Consortium (BARC) type 2-5 bleeding. The secondary outcome was major adverse cardiovascular or cerebrovascular events (MACCE), which included cardiac death, nonfatal myocardial infarction, ischemia-driven target vessel revascularization, all-cause death, stent thrombosis, and stroke during the 6-month follow-up.

A total of 1042 patients were enrolled and analyzed (DPI, 522; DAPT, 520). Low-dose rivaroxaban (10 mg daily) plus clopidogrel was non-inferior to DAPT in BARC type 2-5 bleeding [8 (1.5%) vs. 6 (1.2%), absolute risk difference 0.38%, 95% confidence interval (CI) (- 1.02-1.78), p < 0.0001 for non-inferiority]. Abdominal pain was significantly lower in the DPI group (p = 0.009). Other abdominal discomforts, gastrointestinal bleeding, or MACCE were similar.

In CHD patients with GID undergoing PCI, low-dose rivaroxaban (10 mg daily) plus clopidogrel was non-inferior to DAPT.

Chinese Clinical Trial Registry ChiCTR2100044319. Registered on March 16, 2021.

The antithrombotic strategy for patients with atrial fibrillation (AF) and coronary artery disease following percutaneous coronary intervention is shifting towards less intensive. Nevertheless, for patients with AF and acute coronary syndrome (ACS), an optimal antithrombotic strategy is yet to be established.

We conducted a multi-center cohort study involving 146 Japanese centers that had prospectively registered 460 patients with AF and ACS followed for 2 years. Primary endpoint was the composite of thrombotic and bleeding events, and secondary endpoints included heart failure hospitalization. At the time of study registration, 86 % of participants had received direct oral anticoagulants (DOACs) and 75 % had received aspirin-based triple antithrombotic therapy (TAT) between March 2017 and August 2019. Apixaban was the most frequently used DOAC (29 %). While the proportion of anticoagulants did not change according to the time course, the intensity of antiplatelets significantly attenuated over time (dual antiplatelet at baseline: 75 %, and at 2-years: 7 %). The cumulative incidence of the primary outcome measure was similar in patients with warfarin and DOACs. However, the risk of heart failure hospitalization was significantly higher in those with warfarin compared to DOACs (Hazard ratio: 2.8, 95 % confidence interval: 1.1-5.8, p = 0.022).

The present findings suggest the appropriate optimization of antithrombotic medication balancing in patients with AF and ACS in Japan by reducing the intensity of antiplatelets during the study period.

The combination of antiplatelet and antithrombotic drugs increases the risk of bleeding in patients with atrial fibrillation after coronary drug-eluting stent (DES) implantation. However, the appropriateness of direct-acting oral anticoagulant (DOAC) monotherapy at the time of stent implantation remains uncertain. The objective of this study was to evaluate the safety and efficacy of DOAC monotherapy, specifically using factor Xa inhibitors such as edoxaban, in a low-density lipoprotein receptor knockout (LDL-R-/-) miniature pig model of human-like unstable coronary plaques compared to conventional dual-antiplatelet therapy (DAPT).

We evaluated the safety and efficacy of edoxaban monotherapy in the LDL-R-/- pig model with human-like unstable coronary plaques induced by a high-cholesterol, high-fat diet. Animals underwent DES implantation, followed by four weeks of treatment with either edoxaban monotherapy (3 mg/kg/day) or the DAPT regimen (aspirin 100 mg/day and clopidogrel 75 mg/day). Outcomes were assessed by optical coherence tomography (OCT), virtual histology intravascular ultrasound (iMap-IVUS), and histology. Key endpoints included in-stent thrombus formation, neointimal thickness, and coronary plaque composition.

Edoxaban monotherapy demonstrated a significantly thinner neointimal layer (120.0 [92.5-160.0] μm vs. 210.0 [180.0-240.0] μm, p < 0.001) and smaller neointimal area (1.06 [0.82-1.46] mm2 vs. 1.84 [1.61-2.24] mm2, p < 0.001) compared to DAPT. Neointimal coverage, fibrin deposition, and inflammatory cell infiltration were comparable between groups. No in-stent thrombi were observed in either group. iMap-IVUS findings indicated that edoxaban monotherapy significantly suppressed the increase in lipidic and necrotic plaque area while promoting fibrotic area expansion.

Edoxaban monotherapy demonstrated superior efficacy in suppressing neointimal hyperplasia and stabilizing coronary plaques compared to DAPT with equivalent safety in preventing in-stent thrombus formation. These results provide important preclinical evidence supporting the potential of DOAC monotherapy as an antithrombotic strategy after DES implantation and warrant further investigation in clinical trials.

Guidelines for managing left ventricular thrombus remain limited, particularly when incorporating oral anticoagulants into dual antiplatelet therapy for acute myocardial infarction. This study aims to assess the safety and efficacy of direct oral anticoagulants (DOACs) vs vitamin K antagonists (VKAs) in managing left ventricular thrombus among patients with and without recent myocardial infarction.

This retrospective observational study used data from the TriNetX research network. Patients with left ventricular thrombus treated with either DOACs or VKAs between December 1, 2013 and December 1, 2023, were included. Subgroup analyses were conducted for patients with or without recent acute coronary syndrome (<1 month). Risk and Kaplan-Meier survival analysis were conducted at 90 days after the indexed event.

A total of 39,770 patients were included. DOACs treatment had lower rates of stroke (11.8% vs 13.7%; relative risk [RR] 0.859; 95% confidence interval [CI], 0.816-0.905; P < .001), major bleeding (4.8% vs 5.3%; RR 0.902; 95% CI, 0.829-0.982; P = .018), and systemic embolism (3.5% vs 4.2%; RR 0.841; 95% CI, 0.762-0.928; P = .001) compared with VKAs in overall cohort. Within the acute coronary syndrome group (n = 14,302), DOACs had lower stroke (12.3% vs 14.4%, RR 0.860; 95% CI, 0.791-0.935; P < .0001) and systemic embolism (3.1% vs 4%; RR 0.774; 95% CI, 0.651-0.919; P = .003) risks. For non-acute coronary syndrome group (n = 24,162), DOACs had lower stroke (11.4% vs 13.1%; RR 0.868; 95% CI, 0.811-0.929; P < .001) and major bleeding (4.8% vs 5.5%; RR 0.877; 95% CI, 0.787-0.977; P = .017) risks. No significant differences in all-cause mortality were observed across groups.

DOACs demonstrated better safety and efficacy outcomes when compared with VKAs in left ventricular thrombus treatment, with or without recent acute coronary syndrome.

The "2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes" incorporates new evidence since the "2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction" and the corresponding "2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes" and the "2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction." The "2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes" and the "2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization" retire and replace, respectively, the "2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease."

A comprehensive literature search was conducted from July 2023 to April 2024. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.

Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

Pharmacodynamic drug-drug interactions (PD DDIs) may influence the safety of non-vitamin K antagonist oral anticoagulants (NOACs), but the extent to which PD DDIs increase bleeding risks, remains unclear. Therefore, the impact of PD DDIs on bleeding outcomes in NOAC-treated patients with atrial fibrillation (AF) was investigated.

Using Belgian nationwide data, NOAC-treated AF patients were included between 2013-2019. Concomitant use of PD interacting drugs when initiating NOAC treatment was identified.

Among 193,072 patients, PD DDIs were identified in 114,122 (59.1%) subjects. After multivariable adjustment, concomitant use of PD interacting drugs was associated with significantly higher risks of major or clinically-relevant non-major bleeding (adjusted hazard ratio (aHR) 1.19, 95% confidence interval (CI) (1.13-1.24)), gastrointestinal (aHR 1.12, 95%CI (1.03-1.22)), urogenital (aHR 1.21, 95%CI (1.09-1.35)) and other bleeding (aHR 1.28, 95%CI (1.20-1.36)), compared to NOAC-treated AF patients without PD interacting drug use. Increased bleeding risks were most pronounced with P2Y12 inhibitors (aHR 1.62, 95%CI (1.48-1.77)) and corticosteroids (aHR 1.53, 95%CI (1.42-1.66)), followed by selective serotonin or serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI, aHR 1.26, 95%CI (1.17-1.35)), low-dose aspirin (aHR 1.14, 95%CI (1.08-1.20)) and non-steroidal anti-inflammatory drugs (NSAID, aHR 1.10, 95%CI (1.01-1.21)). Significantly higher intracranial bleeding risks in NOAC users were observed with SSRI/SNRIs (aHR 1.50, 95%CI (1.25-1.81)) and corticosteroids (aHR 1.49, 95%CI (1.21-1.84)).

Concomitant use of PD interacting drugs, especially P2Y12 inhibitors and corticosteroids, was associated with higher major, gastrointestinal, urogenital, and other bleeding risks in NOAC-treated AF patients. Remarkably, higher intracranial bleeding risks were observed with SSRI/SNRIs and corticosteroids.

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.

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.

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.

Percutaneous coronary interventions (PCI) are the mainstay of treating obstructive coronary artery disease. However, procedural planning and individualization of the procedure is necessary for different patient phenotypes to optimize outcomes. Specifically, post-PCI pharmacotherapy with antiplatelets complicates the management of patients at high bleeding risk due to comorbidities, such as atrial fibrillation. Aiming to limit post-procedural adverse events and reduce the procedure-related bleeding risk, several novel technologies and hypotheses have been tested in clinical practice. Such frontiers include limiting the duration of dual antiplatelet therapy or even prescribing single regimens, using drug-coated balloons for performing the intervention and the effect of imaging-guided PCI in optimizing stent expansion. Furthermore, specific instruction in different patient phenotypes, such as atrial fibrillation and chronic kidney disease, are emerging, as despite both pathologies being considered at high bleeding risk, one size does not fit all. Thus, our review will provide all the recent updates on the field as well as algorithms and expert opinions on how to manage this, particularly common, phenotype of patient.

In the US, approximately 10.55 million adults have atrial fibrillation (AF). AF is associated with significantly increased risk of stroke, heart failure, myocardial infarction, dementia, chronic kidney disease, and mortality.

Symptoms of AF include palpitations, dyspnea, chest pain, presyncope, exertional intolerance, and fatigue, although approximately 10% to 40% of people with AF are asymptomatic. AF can be detected incidentally during clinical encounters, with wearable devices, or through interrogation of cardiac implanted electronic devices. In patients presenting with ischemic stroke without diagnosed AF, an implantable loop recorder (ie, subcutaneous telemetry device) can evaluate patients for intermittent AF. The 2023 American College of Cardiology (ACC)/American Heart Association (AHA)/American College of Clinical Pharmacy (ACCP)/Heart Rhythm Society (HRS) Guideline writing group proposed 4 stages of AF evolution: stage 1, at risk, defined as patients with AF-associated risk factors (eg, obesity, hypertension); stage 2, pre-AF, signs of atrial pathology on electrocardiogram or imaging without AF; stage 3, the presence of paroxysmal (recurrent AF episodes lasting ≤7 days) or persistent (continuous AF episode lasting >7 days) AF subtypes; and stage 4, permanent AF. Lifestyle and risk factor modification, including weight loss and exercise, to prevent AF onset, recurrence, and complications are recommended for all stages. In patients with estimated risk of stroke and thromboembolic events of 2% or greater per year, anticoagulation with a vitamin K antagonist or direct oral anticoagulant reduces stroke risk by 60% to 80% compared with placebo. In most patients, a direct oral anticoagulant, such as apixaban, rivaroxaban, or edoxaban, is recommended over warfarin because of lower bleeding risks. Compared with anticoagulation, aspirin is associated with poorer efficacy and is not recommended for stroke prevention. Early rhythm control with antiarrhythmic drugs or catheter ablation to restore and maintain sinus rhythm is recommended by the 2023 ACC/AHA/ACCP/HRS Guideline for some patients with AF. Catheter ablation is first-line therapy in patients with symptomatic paroxysmal AF to improve symptoms and slow progression to persistent AF. Catheter ablation is also recommended for patients with AF who have heart failure with reduced ejection fraction (HFrEF) to improve quality of life, left ventricular systolic function, and cardiovascular outcomes, such as rates of mortality and heart failure hospitalization.

AF is associated with increased rates of stroke, heart failure, and mortality. Lifestyle and risk factor modification are recommended to prevent AF onset, recurrence, and complications, and oral anticoagulants are recommended for those with an estimated risk of stroke or thromboembolic events of 2% or greater per year. Early rhythm control using antiarrhythmic drugs or catheter ablation is recommended in select patients with AF experiencing symptomatic paroxysmal AF or HFrEF.

Underdoses of direct oral anticoagulants (DOAC) are sometimes prescribed due to bleeding risk concerns in patients with atrial fibrillation (AF). We investigated the prevalence of DOAC underdosing and its impact on clinical outcomes in AF patients undergoing percutaneous coronary intervention (PCI).

This multicenter observational cohort study enrolled patients with AF on DOAC undergoing PCI between January 2015 and March 2021 at 15 institutions across Japan. Clinical outcomes within 1 year, including major adverse cardiovascular events (MACE), all-cause mortality, ischemic stroke, and major bleeding events, were evaluated. Of 623 patients enrolled, 167 (26.8%) received underdoses, 224 (36.0%) received appropriate low doses, 210 (33.7%) received appropriate standard doses, and 22 (3.5%) received overdoses. Clinical outcomes were compared between patients with underdoses (n=167) and appropriate doses (n=434). Although the incidence of MACE, all-cause mortality, and major bleeding events did not differ significantly between the 2 groups (log-rank P=0.850, P=0.163, and P=0.711, respectively), ischemic stroke occurred more frequently in the underdose than appropriate-dose group (log-rank P=0.011). After propensity score matching, the same result was observed for the frequency of ischemic stroke (log-rank P=0.026).

Compared with appropriate doses of DOAC, DOAC underdosing was associated with a higher incidence of ischemic stroke, despite no significant difference in MACE, all-cause mortality, and major bleeding events in AF patients undergoing PCI.

Patients with comorbid coronary artery disease and valvular heart disease usually undergo coronary artery bypass grafting alongside valve replacement or ring repair surgeries. Following these procedures, they typically receive a combination of anticoagulation and antiplatelet therapy, which notably heightens their bleeding risk. However, Current scoring systems provide limited predictive capability.

A total of 500 adult patients treated with anticoagulation plus antiplatelet therapy after cardiac surgery were randomly divided into the training set and the validation set at a ratio of 7:3. Predictive factors were identified using univariate logistic regression, LASSO regression and multivariable analysis. Various models were developed, validated and evaluated by using methods including ROC curves, calibration curves, the Hosmer-Lemeshow test, net reclassification improvement (NRI), integrated discrimination improvement (IDI) index, decision curve analysis (DCA) and clinical impact curves (CIC).

Mod2 showed the best performance (AUC of validation set = 0.863) which consists of 8 independent predictive factors (gender, age > 65 years, diabetes, anemia, atrial fibrillation, cardiopulmonary bypass time, intraoperative bleeding and postoperative drainage), with a significantly higher AUC compared to Mod1 (only preoperative factors) and Mod3 (the HAS-BLED scoring model). NRI and IDI analyses further confirmed the superior predictive ability of Mod2 (NRI < 0.05, IDI < 0.05). Both DCA and CIC indicated that Mod2 exhibited good clinical applicability.

This research established and validated a nomogram model incorporating eight predictive factors to evaluate the bleeding risk in patients who receive anticoagulation combined with antiplatelet therapy following cardiac surgery. The model holds significant potential for clinical applications in bleeding risk assessment, decision-making and personalized treatment strategies.

Utilization of cangrelor following coronary artery stent placement as a bridge to cardiac surgery has been previously described in the literature. However, the use of cangrelor as bridge therapy to cardiac surgery for endovascular revascularization is lacking. We describe a case involving a 47-year-old female who developed a left lower extremity tibioperoneal trunk non-obstructing arterial dissection following extracorporeal membrane oxygenation decannulation, requiring repair with a Viabahn endoprosthesis. To maintain stent patency, as well as treat the patient's multi-vessel coronary disease and left ventricular thrombus, triple therapy with cangrelor, aspirin, and bivalirudin was utilized as the patient was optimized for a coronary artery bypass procedure. Our case describes a unique antiplatelet and anticoagulation strategy in a complex patient involving a multi-disciplinary team.

Despite consistent recommendations from clinical guidelines, data from randomized trials on a long-term antithrombotic treatment strategy for patients with atrial fibrillation and stable coronary artery disease are still lacking.

We conducted a multicenter, open-label, adjudicator-masked, randomized trial comparing edoxaban monotherapy with dual antithrombotic therapy (edoxaban plus a single antiplatelet agent) in patients with atrial fibrillation and stable coronary artery disease (defined as coronary artery disease previously treated with revascularization or managed medically). The risk of stroke was assessed on the basis of the CHA2DS2-VASc score (scores range from 0 to 9, with higher scores indicating a greater risk of stroke). The primary outcome was a composite of death from any cause, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, and major bleeding or clinically relevant nonmajor bleeding at 12 months. Secondary outcomes included a composite of major ischemic events and the safety outcome of major bleeding or clinically relevant nonmajor bleeding.

We assigned 524 patients to the edoxaban monotherapy group and 516 patients to the dual antithrombotic therapy group at 18 sites in South Korea. The mean age of the patients was 72.1 years, 22.9% were women, and the mean CHA2DS2-VASc score was 4.3. At 12 months, a primary-outcome event had occurred in 34 patients (Kaplan-Meier estimate, 6.8%) assigned to edoxaban monotherapy and in 79 patients (16.2%) assigned to dual antithrombotic therapy (hazard ratio, 0.44; 95% confidence interval [CI], 0.30 to 0.65; P<0.001). The cumulative incidence of major ischemic events at 12 months appeared to be similar in the trial groups. Major bleeding or clinically relevant nonmajor bleeding occurred in 23 patients (Kaplan-Meier estimate, 4.7%) in the edoxaban monotherapy group and in 70 patients (14.2%) in the dual antithrombotic therapy group (hazard ratio, 0.34; 95% CI, 0.22 to 0.53).

In patients with atrial fibrillation and stable coronary artery disease, edoxaban monotherapy led to a lower risk of a composite of death from any cause, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, or major bleeding or clinically relevant nonmajor bleeding at 12 months than dual antithrombotic therapy. (Funded by the CardioVascular Research Foundation and others; EPIC-CAD ClinicalTrials.gov number, NCT03718559.).

Atrial fibrillation (AF) and coronary artery disease are frequently associated and, when so, lead to a grim prognosis. Recent studies suggest the presence of interconnected pathophysiological pathways between the 2 conditions that can promote and aggravate each other, igniting a vicious cycle. Notwithstanding, in contrast with the attention dedicated to the management of antithrombotic treatment, research on other aspects of coronary artery disease in AF is only recently gaining traction. The clinical impact of correct assessment of coronary artery stenosis in AF is especially high, due to the antithrombotic therapy imposed by both AF and coronary stenting. Until recently, an in-depth characterization of coronary microcirculation in AF was lacking. However, contemporary studies indicate that coronary microvascular dysfunction is a frequent encounter in AF, possibly explaining the ischemic symptoms even in the absence of obstructive coronary artery disease and interfering with the use of pressure-based indices to evaluate the hemodynamic significance of coronary artery stenosis. This comprehensive review addresses our current knowledge on coronary physiology in AF and its repercussion on the invasive management of coronary artery disease in this setting.

Antithrombotic treatment in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) poses a dilemma. We compared outcomes of dual antithrombotic therapy (DAT) (direct oral anticoagulants (DOACs)/warfarin + antiplatelets) vs triple antithrombotic therapy (TAT) (DOACs/warfarin, aspirin, and P2Y12 inhibitor) in this population. Multiple databases were searched from inception to December 17, 2023 to identify randomized controlled trials (RCTs) comparing DAT vs TAT in patients with AF and ACS. Outcomes included major adverse cardiac events (MACE), bleeding events, stroke, stent thrombosis, and myocardial infarction (MI). Relative risk and 95% confidence intervals were estimated with a random-effects model using the inverse-variance technique. We assigned I2 > 50% as an indicator of statistical heterogeneity. p-Value <0.05 was considered significant. Ten RCTs comprising 6186 patients on TAT (female 26%, mean age 71 ± 9 years) and 6800 patients on DAT (female 27%, mean age 71 ± 9 years) were included. Patients receiving DAT experienced lower rates of bleeding events compared to those receiving TAT, with relative risks of 0.69 [0.55-0.87] (p < 0.001), 0.65 [0.40-1.06] (p = 0.09), and 0.62 [0.46-0.84] (p < 0.001) for TAT durations of 3, 6, and 12 months, respectively. No difference was seen in the occurrence of MACE, MI, stroke, or stent thrombosis between DAT and TAT across all three durations of TAT. This is the largest pooled analysis comparing TAT to DAT stratified by the duration of antithrombotic therapy. Our results revealed that DAT was associated with reduced bleeding risk despite no difference in other outcomes.

Many countries have published clinical practice guidelines for appropriate clinical decisions, optimal treatment, and improved clinical outcomes in patients with acute coronary syndrome. Developing guidelines that are specifically tailored to the Korean environment is crucial, considering the treatment system, available medications and medical devices, racial differences, and level of language communication. In 2017, the Korean Society of Myocardial Infarction established a guideline development committee. However, at that time, it was not feasible to develop guidelines, owing to the lack of knowledge and experience in guideline development and the absence of methodology experts. In 2022, the National Evidence-Based Healthcare Collaborating Agency collaborated with a relevant academic association to develop internationally reliable guidelines, with strict adherence to the methodology for evidence-based guideline development. The first Korean acute coronary syndrome guideline starts from the 9 key questions for pharmacotherapy.

Obesity and underweight are a growing health problem worldwide and a challenge for clinicians concerning antithrombotic therapy, due to the associated risks of thrombosis and/or bleeding. This clinical consensus statement updates a previous one published in 2018, by reviewing the most recent evidence on antithrombotic drugs based on body size categories according to the World Health Organization classification. The document focuses mostly on individuals at the extremes of body weight, i.e. underweight and moderate-to-morbid obesity, who require antithrombotic drugs, according to current guidelines, for the treatment or prevention of cardiovascular diseases or venous thromboembolism. Managing antithrombotic therapy or thromboprophylaxis in these individuals is challenging, due to profound changes in body composition, metabolism and organ function, and altered drug pharmacokinetics and pharmacodynamics, as well as weak or no evidence from clinical trials. The document also includes artificial intelligence simulations derived from in silico pharmacokinetic/pharmacodynamic models, which can mimic the pharmacokinetic changes and help identify optimal regimens of antithrombotic drugs for severely underweight or severely obese individuals. Further, bariatric surgery in morbidly obese subjects is frequently performed worldwide. Bariatric surgery causes specific and additional changes in metabolism and gastrointestinal anatomy, depending on the type of the procedure, which can also impact the pharmacokinetics of antithrombotic drugs and their management. Based on existing literature, the document provides consensus statements on optimizing antithrombotic drug management for underweight and all classes of obese patients, while highlighting the current gaps in knowledge in these complex clinical settings, which require personalized medicine and precision pharmacology.

Antithrombotic medications include both antiplatelet and anticoagulants and are used for a wide variety of cardiovascular conditions. A common complication of antithrombotic use is gastrointestinal bleeding. As a result, gastrointestinal prophylaxis is a common consideration for patients on a single or combination antithrombotic regimen. Prophylaxis is typically achieved through use of either proton pump inhibitors or histamine 2 receptor antagonists. Current recommendations for use of gastrointestinal prophylaxis with concomitant use of antithrombotic medications are scarce. In this systematic review, we explore the current evidence and recommendations regarding gastrointestinal prophylaxis for patients on antiplatelet or anticoagulant therapy as well as combination regimens.

To summarize the recent evidence and guideline recommendations on aspirin or P2Y12 inhibitor monotherapy in patients with stable ischemic heart disease and provide insights into future directions on this topic, which involves transition to a personalized assessment of bleeding and thrombotic risks.

It has been questioned whether the evidence for aspirin as the foundational component of secondary prevention in patients with coronary artery disease aligns with contemporary pharmaco-invasive strategies. The recent HOST-EXAM study randomized patients who had received dual antiplatelet therapy for 6 to 18 months without ischemic or major bleeding events to either clopidogrel or aspirin for a further 24 months, and demonstrated that the patients in the clopidogrel arm had significantly lower rates of both thrombotic and bleeding complications compared to those in the aspirin arm. The patient-level PANTHER meta-analysis showed that in patients with established coronary artery disease, P2Y12 inhibitor monotherapy was associated with lower rates of myocardial infarction, stent thrombosis as well as gastrointestinal bleeding and hemorrhagic stroke compared to aspirin monotherapy, albeit with similar rates of all-cause mortality, cardiovascular mortality and major bleeding. Long-term low-dose aspirin is recommended for secondary prevention in patients with stable ischemic heart disease, with clopidogrel monotherapy being acknowledged as a feasible alternative. Dual antiplatelet therapy for six months after percutaneous coronary intervention remains the standard recommendation for patients with stable ischemic heart disease. However, the duration of dual antiplatelet therapy may be shortened and followed by P2Y12 inhibitor monotherapy or prolonged based on individualized evaluation of the patient's risk profile.

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Key pharmacotherapeutic modalities and considerations for the patient with ST-elevation myocardial infarction (STEMI) across the later phases of inpatient care are reviewed.

Published descriptions and validation of clinical pharmacist roles specific to the acute management of STEMI are limited. This high-risk period from presentation through revascularization, stabilization, and hospital discharge involves complex pharmacotherapeutic decision points, many operational medication needs, and multiple layers of quality oversight. A companion article reviewed STEMI pharmacotherapy from emergency department presentation through revascularization. Herein we complete the pharmacotherapy review for the STEMI patient across the inpatient phases of care, including the management of peri-infarction complications with vasoactive and antiarrhythmic agents, considerations for postrevascularization antithrombotics, and assessments of supportive therapies and secondary prevention. Key guideline recommendations and literature developments are summarized from the clinical pharmacist's perspective alongside suggested pharmacist roles and responsibilities. Considerations for successful hospital discharge after STEMI and pharmacist involvement in associated institutional quality improvement efforts are also provided. We aim to support inpatient pharmacy departments in advancing clinical services for this critical patient population and call for further research delineating pharmacists' impact on patient and institutional STEMI outcomes.

Background: Management of oral anticoagulation (OAC) can be challenging, such as in complex cases of nonvalvular atrial fibrillation (NVAF).Materials & methods: A Delphi study comprising two rounds was used for gathering expert opinion through an online questionnaire (83 items grouped in 8 dimensions) on OAC management in specific clinical settings.Results: Consensus was reached for 79 items (95%) in round 1. Experts recommended direct-acting oral anticoagulants (DOACs) for pericardioversion, uninterrupted OAC for catheter ablation, and dual therapy with a DOAC and clopidogrel after percutaneous coronary intervention. They also recommended restarting OAC with a DOAC after an intracranial haemorrhage.Conclusion: The expert-based recommendations obtained may contribute to standardizing and guiding the management of OAC in complex clinical situations in cardiology.