Risk of spontaneous intracerebral hemorrhage associated with NOACs compared with aspirin and warfarin: A long-term single hospital follow-up study.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) are currently the mainstay treatment for preventing thrombosis-induced ischemic stroke in patients with atrial fibrillation (AF), deep vein thrombosis (DVT), or previous infarction. However, such management may potentially induce antithrombotic-associated intracranial hemorrhage, leading to significantly adverse clinical outcomes. To investigate the risk of spontaneous intracranial hemorrhage (sICH) in patients under therapeutic anticoagulation. METHODS: This retrospective cohort study used a database established by Kaohsiung Veterans General Hospital to estimate the risk of first onset sICH in patients with AF, DVT or previous stroke who were 18 years old or older, and who had been on at least three months continuous long-term treatment with the oral anticoagulants aspirin, warfarin, or NOACs. In addition, we used propensity-score matching to minimize bias and Cox proportional hazards ratio to compare the risk of sICH among patients prescribed these anticoagulants. RESULTS: We analyzed the data of 546 patients (182 aspirin users, 182 warfarin users, and 182 NOAC users). 180 (20 taking aspirin, 74 warfarin, and 86 NOACs) developed new onset sICH before seven years. No new onset cases were found after 7 years. Importantly, those taking NOACs were found to be at a higher risk of early onset hemorrhage (47.80 %) compared to the groups taking aspirin (11.10 %) and warfarin (47.80 %) with a median time-to-occurrence being 2.50, 4.00, and 4.40 years, respectively. CONCLUSIONS: Though NOACs prevented ischemic stroke, they were used with a higher risk of early onset spontaneous ICH at our large medical center.

Challenges, Recommendations, and Epidemiology of Pulmonary Embolism in India: A Narrative Review.

An embolized clot that travels to the lungs from the legs or, less commonly, other parts of the body (known as deep vein thrombosis or DVT) causes pulmonary embolism (PE), which is characterized by obstruction of blood flow to the pulmonary artery. As PE has the propensity to masquerade as various illnesses affecting both the cardiovascular (CV) and the respiratory system, it is crucial to identify PE at the earliest. Appropriate diagnosis of PE may lead to earlier treatment and improved patient outcomes. While pulmonary angiography remains the established gold standard for diagnosing PE, the contemporary standard of care for this condition is the computed tomography pulmonary angiogram (CTPA). Anticoagulation therapy is the fundamental strategy for managing PE, with the forefront of treatment being the use of novel and upcoming oral anticoagulants known as non-vitamin K antagonist oral anticoagulants (NOACs). The NOACs provide a practical single-drug treatment strategy, which does not hinder the patient's lifestyle and domestic responsibilities. Although PE may be fatal, early detection may lead to effective management. Despite that, mortality and morbidity associated with PE are very high in India. The awareness among Indian healthcare professionals about PE should be improved, and unified pan-country diagnostic and management guidelines should be formulated to tackle the country's PE burden.

The use of non-vitamin K antagonist oral anticoagulants in chronic thromboembolic pulmonary hypertension: an updated meta-analysis.

Studies have demonstrated the beneficial effects of non-vitamin K antagonist oral anticoagulants (NOACs) for the treatment of atrial fibrillation and venous thromboembolism (VTE). The impact of NOACs on chronic thromboembolic pulmonary hypertension (CTEPH) remains controversial. This meta-analysis was conducted to investigate the effectiveness and safety of NOACs compared with vitamin K antagonists (VKAs) in patients with CTEPH. A comprehensive search of PubMed, Embase, and Cochrane Library was conducted for relevant studies, encompassing data from inception until November 2023. The data were pooled using a fixed-effects model if the I2 value was less than 50%; otherwise, a random-effects model was employed. Overall, two randomized controlled trials (RCTs) and eight observational studies involving 4556 patients with CTEPH were included. Patients receiving NOACs exhibited a significantly lower incidence of all-cause mortality (odds ratio [OR] = 0.52, 95% confidence interval [CI]: 0.36-0.76) and major bleeding (OR = 0.58, 95% CI: 0.36-0.92) compared to those with VKAs. There were no significant differences in the rate of VTE recurrence (OR = 1.07, 95% CI: 0.72-1.59), total bleeding (OR = 0.78, 95% CI: 0.60-1.01), and minor bleeding (OR = 1.11, 95% CI: 0.73-1.69) between the two studied groups. Similar results were found in the subgroup analysis and sensitivity analysis.This meta-analysis provided evidence that NOACs could be superior to VKAs for the treatment of CTEPH. NOACs might be safe and a convenient alternative to VKAs for thromboprophylaxis in patients with CTEPH.

Non-vitamin K versus vitamin K antagonist oral anticoagulants in surgical mitral valve repair or bioprosthetic valve replacement in the first three months after surgery.

INTRODUCTION AND OBJECTIVES: Oral anticoagulation (OAC) with non-vitamin K antagonist oral anticoagulants (NOACs) after surgical mitral valve repair (MVR) or bioprosthetic valve replacement (BVR) in mitral position remains a controversial topic among the cardiovascular community, in particular in the early postoperative period. This study aimed to evaluate the efficacy and safety of NOACs in the first three months after MVR or mitral BVR compared to vitamin K antagonists (VKAs). METHODS: This was a single-center retrospective study with prospectively collected peri-intervention outcomes between 2020 and 2021. Records were retrieved and all participants were contacted by telephone. Patients were divided into groups according to OAC strategy. The primary outcome was a composite of death, rehospitalization, myocardial infarction, stroke or transient ischemic attack, systemic embolism, mitral thrombosis, or bleeding during the first three months after surgery. RESULTS: A total of 148 patients were enrolled, with a mean age of 65.5±12.2 years, 56.8% male. On discharge, 98 (66.2%) patients were on VKAs and 50 (33.8%) were on DOACs for at least three months. The primary outcome occurred in 22 (22.4%) patients in the VKA group and in three (6%) in the NOAC group (p=0.012), mainly driven by more bleeding events in the former. Independent predictors of the primary outcome were smoking (p=0.028) and OAC with VKAs at discharge, the latter predicting three times more events (p=0.046, OR 3.72, 95% CI 1.02-13.5). CONCLUSIONS: NOACs were associated with fewer events, supporting their efficacy and safety during the first three months after surgical MVR or mitral BVR.

Safety and efficacy of concomitant treatment with non-vitamin K antagonist oral anticoagulants and antiseizure medications: A propensity score matching cohort study.

Research on cerebrovascular events in atrial fibrillation (AF) patients taking non-vitamin K antagonist oral anticoagulants (NOACs) with antiseizure medications (ASMs) is limited, highlighting a significant gap in literature. We assessed thrombotic and hemorrhagic risks in patients on NOACs and ASMs versus those on NOACs or ASMs alone. We analyzed a retrospective cohort from five centers, including AF and epilepsy patients on both medications (n = 188), AF patients on NOACs (n = 298), and epilepsy patients on ASMs (n = 50), with a 3-year follow-up. Propensity score matching adjusted for cardiovascular risk differences. The primary outcomes were ischemic stroke, transient ischemic attack, and major bleeding. Results showed the ASM+NOAC group had a higher risk of primary outcomes compared to the NOAC-only group (5.68% vs. 1.18%, hazard ratio = 5.72, 95% confidence interval = 2.22-14.73), with no events in the ASM-only group. This suggests an increased risk for patients on combined NOAC and ASM therapy, underlining the need for careful drug interaction consideration.

Utility of TTR-INR guided warfarin adjustment protocol to improve time in therapeutic range in patients with atrial fibrillation receiving warfarin.

Warfarin remains the most prescribed oral anticoagulant of choice in atrial fibrillation (AF) patient in resource-limited settings. Despite evidence linking Time in Therapeutic Range (TTR) to patient outcomes, its use in clinical practice is not widespread. This prospective study explores the impact of a TTR-INR guided Warfarin adjustment protocol on TTR in AF patients. Conducted at the Warfarin clinic of King Chulalongkorn Memorial Hospital. TTR was calculated using the Rosendaal linear interpolation method at baseline, and then at 6 and 12 months post-protocol implementation. The primary outcome was the improvement in TTR following the protocol's implementation. The study analyzed 57 patients, with a mean age of 72 years and an even gender distribution. At baseline, 53% of patients had a TTR of less than 65%. However, TTR significantly improved from 65% at baseline to 80% after 12 months of protocol implementation (p < 0.001). Furthermore, there was a significant increase in the proportion of patients with a TTR of 65% or more, from 47 to 88% (p < 0.001). During the follow-up period in the first 12 months, three patients died, but no ischemic or major bleeding events occurred. The significant improvement in TTR after 12 months of protocol implementation suggests that this strategy could provide additional value in improving TTR and outcomes in AF patients receiving Warfarin.

Oral anticoagulants and cognitive impairment in patients with atrial fibrillation: A systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: This systematic review assesses the likelihood of developing dementia and cognitive impairment in patients with atrial fibrillation (AF) receiving non-vitamin K antagonist oral anticoagulants (NOACs) as opposed to vitamin K antagonists (VKAs). METHODS: We performed a systematic review with meta-analysis and trial sequential analysis (TSA), which encompassed both randomized controlled trials (RCTs) and observational studies. The objective was to assess the impact of NOACs and VKAs on the incidence of dementia in individuals diagnosed with AF. RESULTS: Out of 1914 studies that were screened, 31 studies were included in the final analysis, which consisted of nine RCTs or their subsequent post-hoc analyses, in addition to 22 observational studies. The meta-analysis shows that NOACs were associated with a decreased probability of developing dementia of any cause [Rate Ratio (RR): 0.88; 95 % confidence interval (95 % CI): 0.82-0.94], especially in patients below the age of 75 (RR: 0.78; 95 % CI: 0.73-0.84). Consistent patterns were observed across all forms of dementia and cognitive function decline. The overall evidence indicates notable variability in the outcome with a moderate-to-low degree of certainty. The TSA suggests that the total sample size of the included trials (155,647 patients) was significantly smaller than the required information size of 784,692 patients to discern the true effect of NOAC versus VKA in terms of reducing dementia risk. CONCLUSION: NOACs may reduce the likelihood of developing dementia in patients with AF, particularly in those under the age of 75. This review highlights the urgent necessity for thorough research to determine the efficacy of NOACs in safeguarding cognitive health.

Ex Vivo Antiplatelet Effects of Oral Anticoagulants.

BACKGROUND: The impact of non-vitamin K antagonist oral anticoagulants (NOACs) on platelet function is still unclear. We conducted a comprehensive ex vivo study aimed at assessing the effect of the four currently marketed NOACs on platelet function. METHODS: We incubated blood samples from healthy donors with concentrations of NOACs (50, 150 and 250 ng/mL), in the range of those achieved in the plasma of patients during therapy. We evaluated generation of thrombin; light transmittance platelet aggregation (LTA) in response to adenosine diphosphate (ADP), thrombin receptor-activating peptide (TRAP), human γ-thrombin (THR) and tissue factor (TF); generation of thromboxane (TX)B2; and expression of protease-activated receptor (PAR)-1 and P-selectin on the platelet surface. RESULTS: All NOACs concentration-dependently reduced thrombin generation compared with control. THR-induced LTA was suppressed by the addition of dabigatran at any concentration, while TF-induced LTA was reduced by factor-Xa inhibitors. ADP- and TRAP-induced LTA was not modified by NOACs. TXB2 generation was reduced by all NOACs, particularly at the highest concentrations. We found a concentration-dependent increase in PAR-1 expression after incubation with dabigatran, mainly at the highest concentrations, but not with FXa inhibitors; P-selectin expression was not changed by any drugs. CONCLUSIONS: Treatment with the NOACs is associated with measurable ex vivo changes in platelet function, arguing for antiplatelet effects beyond the well-known anticoagulant activities of these drugs. There are differences, however, among the NOACs, especially between dabigatran and the FXa inhibitors.

Acute Kidney Injury in Different Anticoagulation Strategies: A Large-Scale Pharmacoepidemiologic Study Using Real-World Data.

PURPOSE: Acute kidney injury (AKI) following anticoagulant application has received growing attention as a significant emerging complication of anticoagulation. Nevertheless, there remains a lack of real-world studies to compare the incidence, clinical features, and prognosis of AKI across different anticoagulant regimens. METHODS: Disproportionality analysis and Bayesian analysis were used to identify suspected AKI cases after different anticoagulant use within the Food and Drug Administration's Adverse Event Reporting System from January 2004 to March 2023. The time to onset, fatality, and hospitalization rates of anticoagulant-associated AKI were also investigated. RESULTS: We identified 9313 anticoagulant-associated AKIs, which appeared to influence mostly patients over 65 years old (65.37%). Lepirudin displayed a stronger AKI association than others, based on the highest reporting odds ratio (ROR = 6.66, 95% CI = 3.97-11.18), proportional reporting ratio (PRR = 6.08, χ2 = 69.12), and empirical Bayes geometric mean (EBGM = 6.08, the lower 90% one-sided CI = 3.95). Warfarin showed the slightest association with AKI in oral anticoagulants, lower than any direct oral anticoagulants excluding apixaban. Edoxaban exhibited the highest potential renal risk among direct oral anticoagulants, with an ROR of 3.32 (95% CI = 2.95-3.72). The median time to AKI onset was 36 (IQR 7-205) days following the initiation of anticoagulation therapy, and most AKI cases occurred within the first month. CONCLUSION: Particular attention should be directed toward monitoring renal function in individuals receiving anticoagulants, including warfarin and direct oral anticoagulants, as well as other anticoagulant agents. This diligence is particularly imperative within the first month after anticoagulant administration for individuals with a tendency for AKI.

The use of andexanet alpha in the Polish setting: An interdisciplinary protocol. Expert consensus statement of the Polish Cardiac Society.

Andexanet alfa (AA) is a recombinant inactive analog of human activated factor X (FXa), effectively reversing the effects of its inhibitors - rivaroxaban and apixaban, which are available in Poland. The drug was approved for clinical use registration after the publication of the results of the ANNEXA-4 trial (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXa Inhibitors 4), in which its efficacy in restoring hemostasis in life-threatening hemorrhages in patients receiving using the aforementioned anticoagulants was demonstrated. Hence, AA is now recommended for patients on apixaban or rivaroxaban therapy with massive and uncontrollable hemorrhages, including hemorrhagic strokes (HS) and gastrointestinal bleeding. Drug-specific chromogenic anti-Xa assays are generally best suited for estimating rivaroxaban and apixaban plasma levels, aside from direct assessment of their concentrations. The absence of anti-Xa activity, determined using these assays, allows us to rule out the presence of clinically relevant plasma concentrations of any FXa inhibitor. On the other hand, the dose of AA should not be modified based on the results of coagulation tests, as it depends solely on the time that elapsed since the last dose of FXa inhibitor and oon the dose and type of FXa inhibitor. AA is administered as an intravenous (i.v.) bolus, followed by an i.v. infusion of the drug. The maximum reversal of anti-Xa activity occurs within two minutes of the end of the bolus treatment, with the continuation of the continuous i.v. infusion allowing the effect to be maintained for up to two hours afterwards. Because anticoagulant activity can reappear after the infusion is completed, it is currently unclear at what point after AA administration FXa inhibitors or heparin should be re-administered. In Poland AA is starting to become available and its urgent need to administer it to patients with severe bleeding on apixaban or rivaroxaban.

Prescribing patterns in patients with chronic obstructive pulmonary disease and atrial fibrillation.

Patients with chronic obstructive pulmonary disease (COPD) had higher risk of atrial fibrillation (AF). The treatment of AF includes medicines to control heart rate and reduce the risk of stroke, and procedures such as cardioversion to restore normal heart rhythm. To reduce the stroke, patients with AF may prescribe some type of antithrombotic medication (such as warfarin, one of the new non-vitamin K antagonist oral anticoagulants [NOACs] - dabigitran, apixaban, rivoraxaban, or edoxaban) or maybe aspirin. The aim of our study was to exam the prescription pattern in patients with COPD and AF. We selected COPD population in Taiwan older than 40 years and less than 90 years old with an COPD diagnosis at least two outpatient claims or at least one inpatient claim coded and also need at least one prescription of bronchodilators. We followed this COPD cohort until they have AF and their prescription pattern. We included 267,740 patients with COPD who meet the inclusion and exclusion criteria and 6,582 patients concomitant with COPD and AF. The mean age was 75 years, and about 77% of the patients were older than 70 years. Three-fourths of patients with COPD were male. The common comorbidities were hypertension (17.58%), diabetes (7.47%), ischemic heart disease (4.66%), and dyslipidemia (3.68%). we found that most patients received aspirin which accounting for 31%, followed by coumadin (8.22%) and clopidogrel. Prescribing NOAC within 30 days after AF diagnosis was low in patients with COPD and the percentage of NOAC usage was also lower than warfarin.

Managing older people with atrial fibrillation and preventing stroke: a review of anticoagulation approaches.

INTRODUCTION: Oral anticoagulants (OACs) are the cornerstone of stroke prevention in atrial fibrillation (AF), but prescribing decisions in older people are complicated. Clinicians must assess the net clinical benefit of OAC in the context of multiple chronic conditions, polypharmacy, frailty and life expectancy. The under-representation of high-risk, older adult sub-populations in clinical trials presents the challenge of choosing the right OAC, where a 'one-size-fits-all' approach cannot be taken. AREAS COVERED: This review discusses OAC approaches for stroke prevention in older people with AF and presents a prescribing aid to support clinicians' decision-making. High-risk older adults with multiple chronic conditions, specifically chronic kidney disease, dementia/cognitive impairment, previous stroke/transient ischemic attack or intracranial hemorrhage, polypharmacy, frailty, low body weight, high falls risk, and those aged ≥75 years are considered. EXPERT OPINION: Non-vitamin K antagonist OACs are the preferred first-line OAC in older adults with AF, including high-risk subpopulations, after individual assessment of stroke and bleeding risk, except those with mechanical heart valves and moderate-to-severe mitral stenosis. Head-to-head comparisons of NOACs are not available, therefore the choice of drug (and dose) should be based on an individual's risk (stroke and bleeding) and incorporate their treatment preferences. Treatment decisions must be person-centered and principles of shared decision-making applied.

A cross-sectional study of appropriateness evaluation of anticoagulation therapy for inpatients with nonvalvular atrial fibrillation.

Background: Oral anticoagulants (OACs) are essential for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). However, the appropriateness of anticoagulation treatment in locally practice remains unclear. This study evaluated compliance with anticoagulation therapy concerning the guidelines and drug labels in patients with NVAF. Methods: Hospitalized patients diagnosed with NVAF between 1 November 2020, and 31 December 2021, were retrospectively enrolled. The appropriateness of anticoagulation regimens at discharge was evaluated based on a flowchart designed according to atrial fibrillation (AF) guidelines and medication labels. Furthermore, we explored factors potentially influencing the "no-use of OACs" using binary logistic regression and verified anticoagulation-related issues through a physician questionnaire. Results: A total of 536 patients were enrolled in this study, including 254 patients (47.4%) with inappropriate anticoagulation regimens. 112 patients (20.9%) were categorized as "underdosing-use of OACs," 134 (25%) who needed anticoagulation therapy were "no-use of OACs" and eight (1.5%) were "over-use of OACs." The results of a binary logistic regression analysis showed that paroxysmal AF (odds ratio [OR], 7.74; 95% confidence interval [CI], 4.57-13.10), increased blood creatinine levels (OR, 1.88; 95% CI, 1.11-3.16), hospitalized pacemaker implantation (OR, 6.76; 95% CI, 2.67-17.11), percutaneous coronary intervention (OR, 3.35; 95% CI, 1.44-7.80), and an increased HAS-BLED score (OR, 1.62; 95% CI, 1.11-2.35) were associated with "no-use of OACs" in patients with NVAF who had indications for anticoagulation therapy. Conclusion: For patients with NVAF with severe renal dysfunction and paroxysmal AF, anticoagulation therapy was inadequate. The underdosing-use of OACs in patients with NVAF was frequently observed. We recommend an anticoagulation management team to tailor anticoagulation regimens to suit each patient's needs.

Comparative safety and effectiveness of non-vitamin K oral anticoagulants versus warfarin in patients with non-valvular atrial fibrillation: A network meta-analysis.

BACKGROUND: The introduction of non-vitamin K antagonist oral anticoagulants (NOACs), with a non-inferior or superior clinical efficacy profile compared to vitamin K antagonists (VKAs), has significantly improved the safety profile and treatment adherence of patients with non-valvular atrial fibrillation (AF). However, few studies have compared the effectiveness and safety of NOACs. Therefore, we conducted this systematic review and network meta-analysis to compare the safety and clinical effectiveness of NOACs and VKAs in patients with non-valvular AF. METHODS: An online bibliographic search was conducted to retrieve real-world evidence studies published between January 2019 and June 2022. RESULTS: Dabigatran was associated with lower risks of major bleeding, ischemic stroke, and intracranial hemorrhage than warfarin. Among the NOACs, only dabigatran had a lower risk of all-cause mortality than warfarin. Dabigatran was also associated with lower risks of major bleeding and intracranial hemorrhage than rivaroxaban. CONCLUSION: Our meta-analysis confirms that dabigatran's real-world safety and clinical effectiveness align with the results of pivotal clinical trials.

A novel shared decision-making (SDM) tool for anticoagulation management in atrial fibrillation: protocol for a prospective, cluster randomized controlled trial.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia that requires anticoagulation therapy to prevent stroke. However, there is still a significant under-/over-treatment in stroke prevention for patients with AF. The adherence and the risk of bleeding associated with oral anticoagulation therapy (OACs) are major concerns. Shared decision-making (SDM) is an approach that involves patients and healthcare providers in making decisions about treatment options. This study aims to assess the effectiveness of a novel SDM tool for anticoagulation management in AF. METHODS: The study will be a prospective, cluster randomized controlled trial involving 440 patients with AF in 8 community health service centers (clusters) in Shanghai, China. The SDM group will receive anticoagulation management through the novel SDM tool, while the control group will receive standard care. The follow-up period will be at least 2 years. The primary outcome will be any bleeding event, while secondary outcomes include the accordance of stroke prophylaxis for AF according to the current guidelines, time in therapeutic range (TTR), the occurrences of major bleeding and thrombosis events, and patient knowledge, adherence, and satisfaction. DISCUSSION: This study will provide evidence of the effectiveness of shared decision-making in improving the appropriateness of OAC use in Chinese AF patients. The findings may inform the development of guidelines and policies for the management of AF and anticoagulation therapy in China and other countries. TRIAL REGISTRATION: ChiCTR ChiCTR2200062123. Registered on 23 July 2022.

Reducing bleeding risk in patients on oral anticoagulation therapy.

INTRODUCTION: Oral anticoagulation (OAC) significantly mitigates thromboembolism risks in atrial fibrillation (AF) and venous thromboembolism (VTE) patients yet concern about major bleeding events persist. In fact, clinically relevant hemorrhages can be life-threatening. Bleeding risk is dynamic and influenced by factors such as age, new comorbidities, and drug therapies, and should not be assessed solely based on static baseline factors. AREAS COVERED: We comprehensively review the bleeding risk associated with OAC therapy. Emphasizing the importance of assessing both thromboembolic and bleeding risks, we present clinical tools for estimating stroke and systemic embolism (SSE) and bleeding risk in AF and VTE patients. We also address overlapping risk factors and the dynamic nature of bleeding risk. EXPERT OPINION: The OAC management is undergoing constant transformation, motivated by the primary objective of mitigating thromboembolism and bleeding hazards, thereby amplifying patient safety throughout the course of treatment. The future of OAC embraces personalized approaches and innovative therapies, driven by advanced pathophysiological insights and technological progress. This holds promise for improving patient outcomes and revolutionizing anticoagulation practices.

Edoxaban treatment in atrial fibrillation in routine clinical care: One-year outcomes of the prospective observational ETNA-AF study in South Korean patients.

Background: The real-world outcomes of edoxaban treatment in patients with atrial fibrillation (AF) were analyzed in the ETNA-AF (Edoxaban Treatment in Routine Clinical Practice) study involving data from multiple regional registries. This report addresses effectiveness and safety of edoxaban in the Korean ETNA-AF population. Methods: One-year data from 1887 Korean ETNA-AF participants were analyzed according to edoxaban dose and patient age and compared with results of other ETNA-AF registries. Results: Approximately 70% of patients received the recommended doses of edoxaban (60 mg/30 mg); non-recommended 60 mg and 30 mg doses were prescribed to 9.6% and 19.8% of the patients, respectively. The proportions of reference age (<65 years), youngest-old (65-74 years) and middle-old/oldest-old (≥75 years) groups were 21.4%, 40.2%, and 38.4%, respectively. Incidence of major or clinically relevant nonmajor bleeding was similar within dose (0.57%-1.71%) and age subgroups (1.26%-1.63%). Incidence of net clinical outcome, a composite of stroke, systemic embolic event, major bleeding, and all-cause mortality, was also comparable among dose subgroups (1.14%-3.10%) and age subgroups (2.28%-2.78%). The percentage of Korean patients receiving non-recommended 30 mg (19.8%) was over twice that of the European population (8.4%). However, the clinical outcomes were generally similar among different populations included in the ETNA-AF study. Conclusions: The outcomes in the Korean ETNA-AF population are like those in the global ETNA-AF population, with overall low event rates of stroke, major bleeding and all-cause mortality across age and dose subgroups. Edoxaban can be used effectively and safely in specific populations of Korean AF patients, including the elderly.

Anticoagulant Treatment in Patients with AF and Very High Thromboembolic Risk in the Era before and after the Introduction of NOAC: Observation at a Polish Reference Centre.

Atrial fibrillation (AF) is associated with an increased risk of stroke. Therefore, patients with AF require appropriate management and anticoagulant therapy. To balance therapy risks and benefits, oral anticoagulants (OAC) treatment should be 'tailored' in patients at a high risk of stroke and bleeding. However, some studies have demonstrated that certain groups of patients do not receive anticoagulants despite the high risk of stroke or thromboembolism. The study aimed to analyse therapeutic methods of stroke prevention in very high-risk patients (CHA2DS2-VASc score of ≥5 in men and ≥6 in women), identify factors predisposing against the use of OACs and assess the administration of anticoagulants before the introduction of non-vitamin K antagonist OAC (NOAC) in 2004-2011 and beyond (years 2012-2019). The analysis covered 2441 patients with AF at a very high thromboembolic risk who were hospitalised in a reference cardiological centre from 2004 to 2019. Data concerning patients' sex, age, comorbidities, type of AF, renal and echocardiographic parameters, reasons for hospitalisation and applied treatment were collected from medical records. HAS-BLED, CHADS2, and CHA2DS2-VASc scores were calculated for all patients. The treatment with oral anticoagulants was compared in the entire population over 2004-2011 and 2012-2019. In this study, a fifth of patients were not treated with OAC. Most patients hospitalised in the years 2012-2019 were treated with OAC. The predictors of not using OAC turned out to be: age of >74 years, heart failure, cancer, paroxysmal AF, and acute coronary syndrome (ACS) or elective coronary angiography/percutaneous coronary intervention (PCI) as a reason for hospitalisation. The introduction of NOAC was associated with a decline in the use of VKA (from 62% to 19.1%) and APT (from 29.1% to 1.3%). This study outlines reasons to initiate OAC treatment in very high-risk patients in clinical practice.

Efficacy and Safety of Oral Anticoagulants in Older Adult Patients With Atrial Fibrillation: Pairwise and Network Meta-Analyses.

OBJECTIVE: To evaluate the efficacy and safety of oral anticoagulants for older adult patients with atrial fibrillation (AF). DESIGN: Pairwise and network meta-analyses. SETTING AND PARTICIPANTS: Patients with AF aged ≥75 years. METHODS: PubMed, Embase, and the Cochrane library were searched for published randomized controlled trials and adjusted observational studies evaluating the use of a non-vitamin K antagonist oral anticoagulants (NOACs), vitamin K antagonist, or antiplatelet drug for the prevention of stroke. The primary efficacy and safety outcomes were the composite of stroke and systemic embolism (SSE) and major bleedings. RESULTS: This study included 38 studies enrolling 1,022,908 older adult patients with AF. Results from pairwise meta-analyses showed that NOACs were superior to warfarin for all outcomes, except that dabigatran increased the risk of gastrointestinal (GI) bleedings. Aspirin was associated with a higher risk of SSE and ischemic stroke than warfarin or NOACs. Results of network meta-analyses indicated that apixaban significantly reduced the risk of SSE, major bleedings, and GI bleedings than warfarin, rivaroxaban, and dabigatran. Apixaban, edoxaban, rivaroxaban, and dabigatran reduced the risk of ischemic stroke and intracranial bleeding compared to warfarin. Dabigatran showed lower risk of all-cause mortality than warfarin and of intracranial bleeding than rivaroxaban. CONCLUSIONS AND IMPLICATIONS: NOACs are of at least equal efficacy, or even superior to warfarin. The safety profile of individual NOAC agents was significantly different, as apixaban performs better than the other oral anticoagulants in reducing major bleeding and GI bleeding, whereas dabigatran increased the risk of GI bleeding.

Characteristics, Thrombus Resolution, and Long-Term Outcomes in Patients with Nonvalvular Atrial Fibrillation and Atrial Thrombus.

To assess the prevalence and management of atrial thrombus in patients with nonvalvular atrial fibrillation (NVAF) and identify the risk factors of the nonresolution of atrial thrombus. This single-center retrospective observational study consecutively enrolled patients with NVAF and atrial thrombus detected using transesophageal echocardiography (TEE) or cardiac computed tomography angiography (CTA) from January 2012 to December 2020. Patients with prior left atrial appendage (LAA) intervention were excluded. The primary endpoint was the presence of atrial thrombus, while the secondary endpoint was the complete resolution of atrial thrombus. The prevalence of atrial thrombus in patients with NVAF was 1.4%. Ninety patients with atrial thrombus (mean age 62.8 ± 11.9 years and 61.1% men) were finally analyzed. Atrial thrombus was in the LAA in 82 (91.1%) patients. During follow up, 60% of the patients showed complete resolution of atrial thrombus. Congestive heart failure (odds ratio [OR]: 8.94; 95% confidence interval [CI]: 1.67-47.80) and a history of ischemic stroke (OR: 8.28; 95% CI: 1.48-46.42) were independently associated with the risk of the nonresolution of atrial thrombus. The presence of atrial thrombus in patients with NVAF who received anticoagulation therapy is non-negligible. Even in anticoagulated patients, TEE or cardiac CTA might still be needed. Congestive heart failure and a history of ischemic stroke are risk factors of the nonresolution of atrial thrombus.