Left atrial appendage closure (LAAC) has become a recommended addition to oral anticoagulation for patients with atrial fibrillation, who undergo cardiac surgery. The procedure significantly reduces the risk of stroke and systemic arterial embolism, potentially making oral anticoagulation (OAC) unnecessary or even harmful, when considering the associated increased risk of bleeding. This publication describes the rationale and design of a randomized trial, testing the hypothesis that stopping OAC is noninferior to continuing OAC after surgical LAAC in terms of the primary endpoint.

The ATLAAC trial is a multicenter, randomized, controlled trial, aiming to enroll 1,220 patients with atrial fibrillation, who have undergone surgical LAAC and remain on OAC. A cardiac CT scan is performed to confirm success of the LAAC. Patients with successful closure are randomized to stop or continue OAC. The primary endpoint is the first occurrence of ischemic stroke, systemic arterial embolism, or major bleeding over an expected mean follow-up of 4 years. Secondary endpoints include all-cause mortality, cardiovascular mortality, any bleeding leading to hospitalization, blood transfusion, venous thromboembolism, myocardial infarction, and quality of life measures.

Enrollment for the ATLAAC trial began in March 2024. As of January 18th, 2025, 554 patients have been enrolled in the study and 319 patients have been randomized. Recruitment is expected to continue for approximately 12 months. Follow-up will be stopped once 128 primary endpoints have occurred.

The ATLAAC trial will evaluate the safety of stopping OAC after surgical LAAC.

EU-CT: 2022-502986-92-00, clinicaltrials.gov ID: NCT06401616.

Transcatheter aortic valve replacement (TAVR) recipients frequently have an indication for long-term oral anticoagulation, including atrial fibrillation or systemic thromboembolic disease. It remains unclear if there are differences in safety and effectiveness between direct oral anticoagulants (DOAC) and warfarin in this patient population.

Clinical outcomes were compared between TAVR recipients receiving DOACs or warfarin using data from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (TVT) registry linked with Centers for Medicare & Medicaid Services claims data. The analysis included patients from the TVT registry who underwent successful TAVR and were discharged on either a DOAC or warfarin between January 2013 and May 2018. The primary outcome was any bleeding requiring hospitalization from discharge to 1 year. Secondary outcomes included all-cause mortality and stroke from discharge to 1 year. Multivariable Cox proportional hazards regression models were used to compare these outcomes between the 2 groups.

A total of 29,142 patients underwent TAVR and were discharged on oral anticoagulation, among whom 10,973 (37.7%) were discharged on a DOAC. The use of DOACs increased throughout the study period and exceed the use of warfarin by the final year (2018). The cumulative incidence of bleeding requiring hospitalization at 1 year (11.8% vs 15.2%, P < .001) and all-cause mortality (15.5% vs 17.5%, P < .001) was significantly lower in DOAC group while stroke (2.47% vs 2.39%, P = .64) was not statistically different between groups. In an adjusted model, the use of a DOAC as opposed to warfarin was associated with a significantly lower risk of bleeding requiring hospitalization (adjusted hazard ratio 0.49, 95% confidence interval 0.43-0.56), all-cause mortality (adjusted hazard ratio 0.61, 95% confidence interval 0.57-0.66), and stroke (adjusted hazard ratio 0.86, 95% confidence interval 0.81-0.92) (all P < .001).

In this analysis of TAVR recipients discharged on oral anticoagulation in a large U.S. registry, the use of a DOAC rather than warfarin was associated with a lower risk of bleeding requiring hospitalization, all-cause mortality, and stroke from discharge to 1 year. Future randomized studies will be necessary to establish the optimal choice of anticoagulant in TAVR patients.

Atrial fibrillation (AF) is a common arrhythmia that disrupts blood circulation in the left atrium (LA), causing stasis in the left atrial appendage (LAA) and increasing thromboembolic risk. In patients at sufficiently high risk, anticoagulation is indicated. This benefit may be counterbalanced by an increased risk of bleeding. Novel anticoagulants under development, such as factor XI/XII inhibitors, may be associated with a lower bleeding risk. However, their efficacy in preventing thrombosis is not fully understood. We hypothesized that patient-specific flow patterns in the LA and LAA not only influence the risk of thrombosis but also the effectiveness of anticoagulation agents.

To test our hypothesis, we simulated blood flow and the intrinsic coagulation pathway in patient-specific LA anatomies with and without factor XI/XII inhibition. We included a heterogeneous cohort of thirteen patients, some in sinus rhythm and others in AF, four of whom had an LAA thrombus or a history of transient ischemic attacks. We used computational fluid dynamics based on 4D CT imaging and a detailed 32-coagulation factor system to run 247 simulations. We analyzed baseline LA flow patterns and evaluated various factor XI/XII inhibition levels. Implementing a novel multi-fidelity coagulation modeling approach accelerated computations by two orders of magnitude, enabling many simulations to be performed.

The simulations provided spatiotemporally resolved maps of thrombin concentration throughout the LA, showing that it peaks inside the LAA. Coagulation metrics based on peak LAA thrombin dynamics suggested patients could be classified as having no, moderate or high thromboembolic risk. High-risk patients had slower flows and higher residence times in the LAA than those with moderate thromboembolic risk, and they required stronger factor XI/XII inhibition to prevent thrombin growth. These data suggest that the anticoagulation effect was also related to the LAA hemodynamics.

The methodology outlined in this study has the potential to enable personalized assessments of coagulation risk and to tailor anticoagulation therapy by analyzing flow dynamics in patient-derived LA models, representing a significant step towards advancing the application of digital twins in cardiovascular medicine.

We compared the effectiveness of direct oral anticoagulants (DOACs) and warfarin for resolving left atrial appendage (LAA) thrombus in patients with acute stroke with non-valvular atrial fibrillation (NVAF).

Among consecutive patients with acute stroke admitted to five major comprehensive stroke centers in Japan between January 2017 and December 2022, those with NVAF and LAA thrombus detected by transesophageal echocardiography (TEE) and underwent follow-up TEE were included. All patients received DOAC or warfarin treatment. We compared the clinical characteristics, changes in LAA thrombus size, resolution, recurrent stroke, and bleeding complications within 3 months of stroke onset.

This study included 63 patients (DOAC group, 22; warfarin group, 41). Sex, age, and National Institutes of Health Stroke Scale scores on admission did not significantly differ between the groups. The initial LAA thrombus size was 0.83 cm2 and 0.88 cm2 in the DOAC and warfarin groups, respectively. On follow-up evaluation 10 days after initial TEE, LAA thrombus was completely resolved in 59 % and 34 % of patients in the DOAC and warfarin groups, respectively (P = 0.02). Multivariable analysis revealed DOAC treatment as an independent factor for LAA thrombus resolution (odds ratio, 3.21; 95 % confidence interval: 1.07-10.23, P = 0.04). Recurrent stroke occurred in one and three patients in the DOAC and warfarin groups, respectively. No intracerebral hemorrhage cases were observed in either group within 3 months of stroke onset.

In patients with acute stroke with NVAF and LAA thrombus detected by TEE, DOACs may be more effective than warfarin in resolving LAA thrombus.

Direct oral anticoagulant (DOAC) agents are established as the anticoagulation strategy of choice for a variety of clinical risks. Despite this, uncertainty still exists with regard to their efficacy and safety for the prevention of stroke and systemic embolism in some patient populations; most notably those with low body weight (LBW) (<60 kg or body mass index [BMI] <18 kg/m2). Currently, there is a paucity of trial and non-trial data to support a prescriptive recommendation for their use in these patient cohorts. We have carried out a pooled systematic review of the most up to date published data of patients stabilized on various DOAC analogs with the view to ascertaining the exact matrices of their efficacy and safety in these cohorts of patients.

We initially carried out a comprehensive search of databases from inception to June 2023 for eligible studies exploring the efficacy and safety of various analogs of direct oral anticoagulants in patients with atrial fibrillation who had low body weight. Databases accessed include PubMed, EMBASE, the Science Citation Index, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effectiveness. We carried out a weighted comparison of derived pooled odd ratios (with their corresponding confidence intervals) of mortality outcomes between various DOACs using the random effects model.

Thirteen studies (n = 165,205 patients) were included in our meta-analysis. DOAC analogs were associated with increased stroke-related events, composite outcome, and mortality in low body weight patients compared to non-low body weight patients (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.17-1.92), (OR 1.55, 95% CI 1.29-1.86), (OR 2.92, 95% CI 1.87-4.58), respectively. There was no significant difference in the safety outcome (major bleeding events) between the DOAC analogs (OR 1.19, 95% CI 0.93-1.52).

In this meta-analytical review comprising both real-world and randomized controlled studies, the use of DOAC analogs in low body weight patients (body weight of <60 kg or BMI<18 kg/m2) with atrial fibrillation was associated with increased risks of stroke-related events, composite outcomes, and mortality compared to non-low body weight cohorts patients. At the same time, there was no significant difference in terms of major bleeding events. This finding has provided the first resolution of pervading uncertainty surrounding the use of DOAC analogs in these patient cohorts and suggests the need for follow-up confirmatory systematic studies in this group of patients.

Some reports suggest that older patients with traumatic brain injury (TBI) are more likely to experience acute intracranial hemorrhage, resulting in poor outcomes. However, the association between precise chronological age and use of antithrombotic agents with acute intracranial hemorrhage in these patients remains unknown. The aim of this study was to determine factors associated with acute intracranial hemorrhage and poor outcomes in patients with TBI, including chronological age and use of antithrombotic agents.

Patients hospitalized for TBI between January 2006 and December 2021 were included. Patients were categorized by age groups of <65 years, 65 to 74 years, 75 to 84 years, and ≥85 years. Associations between each age group and acute intracranial hemorrhage, a poor outcome at discharge, and in-hospital mortality were evaluated.

The cohort included 1086 patients, with 713 (65.7%) in the ≥65 age group. Although chronological age was associated with acute intracranial hemorrhage in patients aged <65 years (odds ratio [OR] 1.02; 95% CI 1.01-1.03), it was not associated with patients aged ≥65 years. None of the antithrombotic agents investigated were associated with acute intracranial hemorrhage in the group aged ≥65 years. Although chronological age was associated with a poor outcome in patients aged <65 years (OR 1.03; 95% CI 1.01-1.07), it was not associated in those aged ≥65 years. The ≥85 year age group (OR 2.30; 95% CI 1.18-4.51) compared with <65 years were significantly associated with a poor outcome. None of the antithrombotic agents investigated were associated with a poor outcome in the group aged ≥65 years.

Our findings confirmed the lack of an association of chronological age and antithrombotic agents with acute intracranial hemorrhage in the group of older adults with TBI. Our findings suggest that antithrombotic agents may be safely used, even in older adults.

Intravenous thrombolysis (IVT) is contraindicated for acute ischemic stroke (AIS) patients taking direct oral anticoagulants (DOACs) within 48 hours before index stroke. Limited data exist on off-label use of IVT for these patients. We compared the safety and outcomes of IVT in AIS patients with DOAC treatment and patients with no OAC before index stroke.

We analyzed data from the Safe Implementations of Treatments in Stroke (SITS) International Stroke Thrombolysis Registry during 2013-2024. Outcomes were symptomatic intracerebral hemorrhage (SICH) by the SITS Monitoring Study and European Cooperative Acute Stroke Study II definitions, functional independency (modified Rankin Scale score 0-2), and death by 3 months. Propensity score matching with a nearest neighbor matching algorithm with a ratio of 1:2 was used for relevant clinical variables. We also analyzed the time from last DOAC dose to IVT treatment.

A total of 1,311 DOAC and 129,384 no OAC patients were included. We matched 894 patients with DOAC to 1,788 with no OAC. The mean age was 75 years versus 76 years, and the median National Institutes of Health Stroke Scale score 11 versus 12, respectively. Patients with DOAC had a similar proportion of outcomes compared with patients with no OAC: SICH per SITS Monitoring Study (1.1 vs 1.5%, p = 0.50), SICH per European Cooperative Acute Stroke Study II (4.0 vs 4.3%, p = 0.82), any parenchymal hematoma (6.3 vs 7.8, p = 0.22), and functional independency (47.9 vs 46.4%, p = 0.59) and death (25.1 vs 24.0%, p = 0.65) at 3-month follow-up. The time from last DOAC dose to IVT did not affect outcomes.

In this observational study, we did not find any difference in outcomes after IVT therapy in AIS patients with DOAC compared with no OAC treatment before index stroke. ANN NEUROL 2025;97:1205-1214.

Atrial fibrillation (AF) disproportionately affects elderly populations, raising concerns about balancing efficacy and safety in anticoagulation therapy.

To assess the efficacy and safety of various anticoagulants in elderly AF patients through a systematic review and network meta-analysis.

We systematically searched PubMed, MEDLINE, Embase, and Web of Science for randomized controlled trials (RCTs) up to September 10, 2024, involving AF patients aged 75 years and older. Outcomes included stroke, major and non-major bleeding, all-cause mortality, and cardiovascular mortality. Statistical analysis was performed using a Bayesian random-effects network meta-analysis model to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Surface under the cumulative ranking curve (SUCRA) was used to rank treatments.

Fourteen RCTs involving 16,261 participants were included, with 13 RCTs analyzing stroke (14675 patients), 14 RCTs major bleeding (16261 patients), 6 RCTs non-major bleeding (1074 patients), 7 RCTs all-cause mortality (10128 patients), and 4 RCTs cardiovascular mortality (7704 patients). Edoxaban 15 mg once daily significantly reduced stroke incidence compared to warfarin (OR = 0.30, 95% CI: 0.12-0.71) and placebo (OR = 0.29, 95% CI: 0.20-0.42), ranking highest in stroke prevention (SUCRA = 90.6%). Dabigatran 110 mg twice daily reduced the risk of major bleeding (OR = 0.18, 95% CI: 0.04-0.76) compared to rivaroxaban 15 mg. Rivaroxaban 10 mg (OR = 0.35, 95% CI: 0.13-0.94) and edoxaban 15 mg (OR = 0.67, 95% CI: 0.46-0.99) demonstrated significant reductions in adverse events compared to placebo. No significant differences were observed across treatments for all-cause or cardiovascular mortality.

Edoxaban 15 mg and Rivaroxaban 10 mg provide an optimal balance between efficacy and safety in elderly AF patients. These findings support the need for personalized anticoagulant selection to maximize therapeutic benefit in this high-risk population.

Anticoagulation therapy reduces stroke risk in patients with atrial fibrillation (AF), but it is often underused in older populations due to concerns about bleeding. This study aimed to compare the safety and effectiveness of anticoagulation during periods of exposure and non-exposure and across different anticoagulants in people with AF aged ≥75 years.

Using UK primary care data from the Clinical Practice Research Datalink (2013-2017), a retrospective cohort study was conducted on patients newly prescribed oral anticoagulants (warfarin or direct oral anticoagulants). Exposure to anticoagulation was mapped using prescription data. Cox regression models were used to estimate adjusted HRs for stroke, bleeding, myocardial infarction, and death during periods of exposure and non-exposure and for different anticoagulants.

Among 20 167 patients (median age 81 years), non-exposure to anticoagulation was associated with higher risks of stroke (HR 3.07, 95% CI 2.39 to 3.93), myocardial infarction (HR 1.85, 95% CI 1.34 to 2.56) and death (HR 2.87, 95% CI 2.63 to 3.12) compared with exposure. Compared with warfarin, apixaban was associated with lower risks of non-major bleeding (HR 0.73, 95% CI 0.64 to 0.85), whereas rivaroxaban was associated with higher risks of major (HR 1.33, 95% CI 1.15 to 1.55) and non-major (HR 1.29, 95% CI 1.16 to 1.44) bleeding.

Non-exposure to anticoagulation increases the risks of stroke, myocardial infarction and death in older patients with AF. Clinicians should carefully weigh the risks of discontinuing anticoagulation and provide shared decision-making support to patients, especially when considering deprescription.

Some East Asian (EA) guidelines recommend lower doses of direct oral anticoagulants (DOACs) for atrial fibrillation (AF) than in North America and Europe.

Investigate the association of immigration from EA with DOAC dosing and outcomes in AF.

Population-based cohort study using administrative databases of Ontario immigrants with AF aged ≥66 years who were dispensed DOAC prescriptions from 2012-2019. Birth country was classified as EA or not. We used multivariable logistic regression to assess the association of EA birth with DOAC dose and cause-specific hazards regression for the association of EA birth and DOAC dose with stroke/bleeding/death. Interaction between EA birth and DOAC dosing was studied for each outcome.

Among 14,421 immigrants, 3958 (27.4%) were born in EA. EA immigrants had lower odds of receiving full-dose DOACs versus non-EA immigrants (OR 0.64, 95%CI 0.58-0.69, p<0.001). EA birth was not associated with a composite of hospitalization for stroke/bleeding (HR 0.97, 95%CI 0.84-1.12, p= 0.67) nor hospitalization for stroke (HR 0.86, 95%CI 0.71-1.04, p= 0.13), but was associated with higher bleeding hazard (HR 1.15, 95%CI 1.02-1.30, p= 0.02) and lower mortality (HR 0.91, 95%CI 0.84-0.99, p= 0.04). There was no significant interaction between EA birth and DOAC dosing for stroke (p=0.41), bleeding (p=0.27), or death (p=0.33).

EA immigrants were less likely to receive full-dose DOACs and had a higher bleeding hazard, similar stroke hazard, and lower mortality risk than non-EA immigrants. There was no evidence that DOAC dosing had a differential treatment effect in EA immigrants.

Atrial fibrillation (AF) is a leading cause of stroke, and oral anticoagulants (OAC) reduce this risk. However, there are limited data on the residual risk of recurrent stroke in patients with AF.

To determine the recurrent stroke risk in patients with AF by performing a systematic review and meta-analysis.

Eligible studies were identified by searching Ovid MEDLINE and Embase from inception (Ovid: January 1946; Embase: January 1970) until January 2025.

Eligible studies enrolled patients with prior ischemic stroke and AF, reported information on incidence of recurrent stroke, and had follow-up data for 1 or more years. Three reviewers independently screened abstracts and performed full-text reviews.

Data extraction was performed by 2 reviewers and independently verified by a third. Incidence rates were pooled using random-effects meta-analysis. Analysis was repeated in patients whose qualifying event occurred despite OAC. Study quality was assessed using the Quality In Prognosis Studies tool.

The primary outcome was recurrent ischemic stroke. The secondary outcomes were any recurrent stroke (ischemic stroke or intra-cerebral hemorrhage [ICH]) and ICH during follow-up.

A total of 23 studies were identified, which included 78 733 patients and 140 307 years of follow-up. The median proportion of OAC use across studies was 92%. The pooled incidence of recurrent ischemic stroke was 3.75% per year (95% CI, 3.17%-4.33%). The risk was higher in noninterventional observational cohorts (4.20% per year; 95% CI, 3.41%-4.99%) compared with randomized clinical trials (2.26% per year; 95% CI, 1.96%-2.57%) (P value for interaction <.001). The risk of any recurrent stroke was 4.88% per year (95% CI, 3.87%-5.90%), and the risk of ICH was 0.58% per year (95% CI, 0.43%-0.73%). In patients with stroke despite OAC, the risk was 7.20% per year (95% CI, 5.05%-9.34%) for ischemic stroke, 8.96% per year (95% CI, 8.25%-9.67%) for any stroke, and 1.40% per year (95% CI, 0.40%-2.40%) for ICH.

In this systematic review and meta-analysis, even with modern prevention therapy, the residual recurrence risk after AF-related stroke is high, with an estimated 1 in 6 patients experiencing a recurrent ischemic stroke at 5 years. These data demonstrate an urgent need to improve our understanding of the biological processes responsible for recurrence, improve risk stratification, and develop new secondary prevention strategies after AF-related stroke.

Aim: Direct oral anticoagulant (DOAC) switching often occurs in patients with nonvalvular atrial fibrillation (NVAF) for medical and nonmedical reasons. Limited data describe the economic consequences of DOAC switching in patients with NVAF. This study evaluates the cost-effectiveness and budget impact of initiating apixaban and switching to rivaroxaban versus initiating and continuing apixaban for patients with NVAF, from a German payer perspective. Materials & methods: Built on an existing model, a cohort-level lifetime Markov model was developed, including dynamic pricing assumptions to account for anticipated generic entry of DOACs. The modeled population (n = 1000) included German patients with NVAF, eligible for oral anticoagulation, who initiated on apixaban. The primary model outcome was the incremental cost-effectiveness ratio, assessed using cost per quality-adjusted life year (QALY) gained and a willingness-to-pay threshold of €48,750/QALY. A secondary model outcome was a 5-year budget impact analysis. Results: Switching patients from apixaban to rivaroxaban led to 285 additional events per 1000 patient years, resulting in 0.079 fewer QALYs and higher total costs per patient (€21,357 vs €16,390 for apixaban continuers). In the base case analysis (with generic pricing assumptions), switching from apixaban to rivaroxaban was dominated (i.e., less effective and more costly) by continuing apixaban. In the budget impact analysis (with generic pricing assumptions), switching from apixaban to rivaroxaban led to additional cumulative costs of €490 per patient over 5 years. Conclusion: Despite the introduction of generic discounting, switching patients with NVAF from apixaban to rivaroxaban led to higher total costs and fewer QALYs under base case assumptions, meaning apixaban switchers were dominated by apixaban continuers from a German payer perspective. Switching patients from apixaban to rivaroxaban also led to greater budget impact over 5 years.

Non-vitamin K oral anticoagulants are recommended over vitamin K antagonists in patients with nonvalvular atrial fibrillation (AF). However, the risk of gastrointestinal bleeding may be higher with non-vitamin K oral anticoagulants versus vitamin K antagonists. Patients after successful transcatheter aortic valve replacement (TAVR) who are elderly and frail have worse outcomes with major gastrointestinal bleeding (MGIB), including death. This study evaluated incidence, predictors, and impact of MGIB among patients with AF after successful TAVR.

This on-treatment analysis of ENVISAGE-TAVI AF (Edoxaban Compared to Standard Care After Heart Valve Replacement Using a Catheter in Patients With Atrial Fibrillation) included patients who received ≥1 dose of the study drug. Demographic, clinical, and procedural characteristics were compared between patients with versus without an MGIB event. Cox multivariable regression analysis identified predictors of MGIB.

Of 1377 patients in this analysis, 83 (6.0%) experienced MGIB, with 56 (67.5%) of these patients receiving edoxaban. Patients with versus without MGIB were more likely to have undergone percutaneous coronary intervention ≤30 days before TAVR (9.6% versus 4.2%; P=0.03), a higher ejection fraction (mean±SD, 58.0±10.4 versus 55.3±11.5; P=0.04), and carotid artery disease (13.3% versus 6.6%; P=0.04). Edoxaban without dose adjustment versus vitamin K antagonist use (P=0.003), smoking (P=0.01), low hemoglobin levels (P<0.0001), and percutaneous coronary intervention ≤30 days before TAVR (P=0.01) emerged as predictors of MGIB.

In this ENVISAGE-TAVI AF subanalysis, MGIB occurred in 6.0% of patients with prevalent or incident AF undergoing TAVR, and those receiving edoxaban versus vitamin K antagonists had a higher risk of MGIB. A priori identification of risk factors for MGIB may help optimize outcomes for patients with AF undergoing TAVR.

URL: https://www.clinicaltrials.gov; unique identifier: NCT02943785.

Atrial fibrillation significantly increases the risk of ischemic stroke, with thrombi primarily originating in the left atrial appendage (LAA). While direct oral anticoagulants (DOACs) are the standard for stroke prevention, LAA occlusion (LAAO) has emerged as a nonpharmacologic alternative, particularly for patients at high bleeding risk. A systematic review and meta-analysis included 15 studies (1 randomized control trial and 14 observational studies) encompassing 22,420 patients (10,704 LAAO, 11,716 DOAC). LAAO and DOACs demonstrated comparable thromboembolic event rates. LAAO was associated with significantly lower risks of stroke/transient ischemic attack (risk ratio: 0.86, P = 0.0004), major bleeding [hazard ratio (HR): 0.74, P = 0.03], cardiovascular mortality (HR: 0.57, P < 0.00001), and all-cause mortality (risk ratio 0.66, P = 0.006). The composite outcome significantly favored LAAO (HR: 0.67, P = 0.0008). No significant difference was found in intracranial bleeding rates.

The prevalence of Alzheimer's Disease (AD) is increasing worldwide, with more emergency providers and neurologists expecting to encounter these patients. The paradigm of management of AD is expected to change given the recent approval of anti-amyloid therapies (AATs). The most concerning complication of these therapies is amyloid-related imaging abnormalities (ARIA), which can lead to an increased risk of cerebrovascular complications. Given a growing population of patients with AD and growing use of AATs, providers must be prepared to manage patients at risk of cerebrovascular disease and those presenting with neurologic deficits. This subpopulation warrants a unique approach given the risk of ischemic stroke and the associated risk of hemorrhage present in the use of AATs. In this narrative review, we present and propose management considerations in the acute stroke setting and patients at risk of cerebrovascular disease, including patients with indications for anticoagulation, to most appropriately manage this special population. Future cross-disciplinary collaboration and use of registry data will be essential to narrow management approaches and develop safety data.

Risk scores have been used to assess stroke risk in atrial fibrillation (AF) for reducing ischemic stroke and bleeding risk. Information gain ratio (IGR) is an entropy-based parameter that shows which clinical score is more informative for prediction of the clinical endpoint.

Herein, we aimed to generate and validate a stroke risk score based on the TuRkish Atrial Fibrillation (TRAF) data.

We used a split-sample approach to develop and internally validate the new stroke risk score. Based on multivariate logistic regression analysis, we generated CHADS-F in the anticoagulation naïve TRAF cohort (274,631 patients). CHADS-F stands for Cardiac failure (1 point), hypertension (1 point), age (≥ 65-69 = 1 point, ≥ 70-74 = 2 points ≥ 75 = 3 points), diabetes (1 point), stroke (2 points), and older female (1 point) (≥ 65). External validation was performed in the "Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF)" Registry. Informative capacity and accuracy of the CHADS-F score was compared with CHADS2 and CHA2DS2-VASc scores.

In anticoagulation naïve cohort, CHADS-F (IGR for all cohort: 0.7526) outperforms both the CHADS2 (IGR for all cohort: 0.6340) and CHA2DS2-VASc (IGR for all cohort: 0.6969) in terms of the IGR for ischemic stroke and systemic embolism. Receiver operating characteristic curves revealed highest accuracy for the CHADS-F score [area under curve for CHADS-F: 0.743, CHADS2: 0.722, and CHA2DS2-VASc: 0.722]. CHADS-F had good discriminative abilities at predicting clinical endpoints in the GARFIELD-AF registry.

The CHADS-F score had higher informative capacity and accuracy than the current CHADS2 and CHA2DS2-VASc scores for predicting stroke and systemic embolism.

Direct oral anticoagulants (DOACs) are the standard treatment for stroke prevention in AF. However, high-quality head-to-head comparisons of DOACs are lacking. This study compared oral anticoagulants in patients with AF.

Data were retrieved from eligible randomised controlled trials (RCTs). Interventions were ranked using the surface under the cumulative ranking curve (SUCRA) and the frequentist random effects model was applied. Efficacy outcomes included stroke, systemic embolism, MI, and all-cause mortality; the safety outcome was major bleeding. A composite outcome of efficacy and net clinical benefit was also evaluated.

From 23,152 records, 11 eligible RCTs were identified and included in the study. Rivaroxaban was superior to vitamin K antagonists (VKA) in net clinical benefit (RR 0.75; 95% CI [0.59-0.94]; p=0.0133), but there were no significant differences between other DOACs and VKA or among the DOACs themselves. Rivaroxaban reduced the risk of the composite outcome of efficacy compared with dabigatran (RR 0.85; 95% CI [0.75-0.98]; p=0.02) and edoxaban (RR 0.84; 95% CI [0.75-0.95]; p=0.0051), but not apixaban (RR 0.89; 95% CI [0.89-1.02]; p=0.087). All DOACs showed superiority over VKA in efficacy, without an increased risk of major bleeding. Based on the SUCRA, rivaroxaban showed a favourable risk-benefit profile compared with the other anticoagulants.

This study showed that DOACs are superior to VKA in efficacy without increasing major bleeding risk, with rivaroxaban demonstrating the most balanced risk-benefit profile. Well-designed RCTs are needed to validate these findings.

Objectives: To assess the association between apixaban use and the risk of stroke/systemic embolism (SE) and major bleeding (MB) compared with other anticoagulants (OACs) across demographic and socio-economic subgroups in the treatment of nonvalvular atrial fibrillation (NVAF). Methods: The study included adult NVAF patients initiating OAC treatment between 2013 and 2019 in the Medicare database. Inverse probability treatment weighted Cox proportional hazard models were used to assess stroke/SE and MB outcomes across various subgroups. Results: Overall, the adjusted risks of stroke/SE and MB were lower for apixaban compared with warfarin (stroke/SE: HR, 0.69, [95% confidence interval (CI): 0.65-0.74], MB: 0.59 [95% CI: 0.57-0.60]), rivaroxaban (stroke/SE: 0.88 [95% CI: 0.84-0.92], MB: 0.60 [95% CI: 0.58-0.61]) and dabigatran (stroke/SE: 0.88 [95% CI: 0.80-0.95], MB: 0.76 [95% CI: 0.72-0.80]). Among the low socio-economic status (SES) group, apixaban was associated with lower risk vs. warfarin (stroke/SE: 0.73 [95% CI: 0.69-0.77], MB: 0.60 [95% CI: 0.57-0.62]) and rivaroxaban (stroke/SE: 0.88 [95% CI: 0.83-0.94], MB: 0.61 [95% CI: 0.59-0.63]). Among medium SES patients, apixaban was associated with lower risk vs. warfarin (stroke/SE: 0.67 [95% CI: 0.63-0.71] MB: 0.60 [95% CI: 0.58-0.63]), rivaroxaban (stroke/SE: 0.85 [95% CI: 0.79-0.91], MB: 0.59 [95% CI: 0.56-0.61]) and dabigatran (stroke/SE: 0.85 [95% CI: 0.73-0.99], MB: 0.77 [95% CI: 0.70-0.84]). Apixaban was also associated with lower risks of stroke/SE and MB compared with other OACs among most other demographic, socio-economic subgroups. Conclusions: Apixaban was associated with lower risk of stroke/SE and MB than warfarin, rivaroxaban, dabigatran across most demographic, socio-economic subgroups.

This study aimed to identify patterns of direct oral anticoagulant (DOAC) and vitamin K antagonist (VKA) use in hospitalized patients and to examine their association with in-hospital haemorrhagic complications and mortality.

An observational cross-sectional study was conducted among hospitalized patients ≥18 years from 2018 to 2022. Data on hospital discharges were obtained from the minimum data set and were matched with pharmacy records to identify patients treated with DOACs or VKAs. In-hospital haemorrhagic complications and mortality rates were calculated for study groups. Multivariate logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95%CIs), adjusting for age, sex and comorbidities. Analyses were stratified by medical and surgical profiles. Statistical significance was set at .05.

The study included 74 190 patients, with 4774 receiving DOACs and 1768 VKAs. During the study period, DOAC use increased by 45.11%. DOAC-treated patients had lower complication rates than those treated with VKAs (1.9 vs. 2.8%, respectively; P = .032). DOAC use was linked to a lower risk of haemorrhagic complications in surgical patients (OR = 0.65; 95%CI: 0.35-0.91), while in medical patients, the reduction in risk was not statistically significant (OR = 0.59; 95%CI: 0.33-1.10). No effect on mortality risk was observed among medical and surgical patients.

The increased use of DOACs among hospitalized patients showed a protective effect against haemorrhagic complications in surgical patients, supporting their increasing use in hospital settings.

Non-vitamin K oral anticoagulants prevent stroke and systemic embolism in patients with nonvalvular atrial fibrillation. However, potential drug interactions with concomitant medications may compromise their efficacy and escalate the risk of adverse effects.

We conducted a territory-wide retrospective cohort study in Hong Kong, focusing on nonvalvular atrial fibrillation prescribed non-vitamin K oral anticoagulants. The objective was to investigate the associated risk of gastrointestinal bleeding, intracranial hemorrhage, hospitalization for major bleeding, and all-cause mortality in relation to various concomitant medications. Our analysis included 22 568 patients with nonvalvular atrial fibrillation (aged 75.7 ± 10.8 years; 51.2% men) taking non-vitamin K oral anticoagulants from January 1, 2017, to December 31, 2020, totaling 40 317 patient-years. It was found that amiodarone (hazard ratio [HR], 1.53), digoxin (HR, 1.30), diltiazem (HR, 1.18), clarithromycin (HR, 4.98), and fluconazole (HR, 2.38) were associated with increased gastrointestinal bleeding, whereas amiodarone (HR, 2.20) and digoxin (HR, 1.61) were associated with increased intracranial hemorrhage. Furthermore, amiodarone (HR, 1.64), digoxin (HR, 1.35), clarithromycin (HR, 4.18), and fluconazole (HR, 2.40) were associated with increased hospitalization for major bleeding. Additionally, amiodarone (HR, 2.65), digoxin (HR, 1.85), diltiazem (HR, 1.44), verapamil (HR, 1.80), antidepressants (HR, 1.31), and fluconazole (HR, 3.27) were associated with increased all-cause mortality. Conversely, dronedarone (HR, 0.56) and atorvastatin (HR, 0.86) were associated with a significant reduction in all-cause mortality.

For patients with nonvalvular atrial fibrillation taking non-vitamin K oral anticoagulants, several concurrent medications were associated with increased risks of intracranial hemorrhage, major bleeding hospitalizations, and overall mortality.

Although the management of atrial fibrillation (AF) has improved over the years, suboptimal adherence to direct oral anticoagulants (DOACs) is a major health concern. Adherence and long-term persistence to DOACs decline over time resulting in increased risks of stroke, major bleeding, and death.

This study aimed to evaluate the association between adherence to DOACs and composite or bleeding events using marginal structural models (MSMs).

A retrospective study was conducted using the Medicare Advantage Plan from January 2016 to December 2020. Patients with AF prescribed any DOACs were identified. Adherence was calculated using the proportion of days covered (PDC). Patients with PDC ≥ 0.80 were considered adherent. Composite (stroke, systemic embolism, acute coronary syndrome) and bleeding (major and minor) events were calculated for each of the 4 time periods. An MSM was conducted to estimate the association between adherence and composite efficacy or bleeding events by controlling for time-dependent covariates and time-dependent exposure affected by the previous exposure.

A total of 1969 patients with AF were included in the study. Adherence was suboptimal during all the 5 time periods, and it ranged from 39.8% to 53.12%. This study did not find any significant association between adherence to DOACs and composite efficacy or bleeding events. The safety and efficacy outcomes were comparable among apixaban, rivaroxaban, and dabigatran.

This study revealed that adherence declined over time among old patients with AF. Future studies should explore the association between adherence to DOACs and health outcomes for a longer duration of follow-up using MSM.

The role of anticoagulation for stroke prevention in patients with device-detected atrial high-rate episodes, also known as subclinical atrial fibrillation (AF), is a subject of equipoise.

To assess the net benefit of nonvitamin K antagonist oral anticoagulants (NOACs) in patients with device-detected subclinical AF.

Decision analytical model run with 10 000 patients with anticoagulation and 10 000 patients without anticoagulation in a clinical scenario of deciding whether to start NOACs for stroke prevention in patients with subclinical AF. A Markov decision model was conducted on October 1, 2024, to estimate net outcomes of NOACs. The patients had stroke risk and bleeding risks similar to those of patients in randomized trials of anticoagulation in subclinical AF.

Anticoagulation was modeled to decrease the risk of ischemic stroke by 32% and increase the risk of major bleeding by 62%. In probabilistic sensitivity analyses, the 95% CIs for treatment effect sizes were also considered.

The main outcome measure for overall net benefit was the cumulative quality-adjusted life-years (QALYs) during the simulation. The model considered the number and severity of ischemic strokes, hemorrhagic strokes, other intracranial bleeds, and extracranial bleeds, as well as the number of deaths during a 10-year simulation.

When comparing the 2 cohorts of 10 000 patients (mean age, 77 years; 3700 [37%] women), those receiving NOAC therapy had 233 fewer ischemic strokes (21.7%), 55 fewer deaths (1.1%), and 453 more major bleeding events (37.3%) over a 10-year simulation period. Per patient, these differences translated to approximately 1 additional quality-adjusted week of life (0.024 QALYs) with NOAC treatment during the 10-year simulation. When the 95% CIs of treatment effect sizes were considered in probabilistic sensitivity analysis, there was a 65.8% probability that NOAC treatment leads to more QALYs than withholding treatment.

In this analytical model study, initiating NOACs in patients with device-detected subclinical AF was associated with a minimal increase in QALYs. However, the benefits were uncertain, and the effect size of the overall net benefit does not appear to be clinically meaningful.

Left atrial appendage occlusion (LAAO) is an alternative to chronic oral anticoagulation (OAT) for stroke prevention in nonvalvular atrial fibrillation (NVAF) patients with contraindications to OAT. Postprocedure antithrombotic therapy (ATT) is essential to reduce the risk of device-related thrombosis (DRT), but the optimal regimen remains uncertain.

This study aims to compare the safety and efficacy of low-dose direct oral anticoagulants (DOACs) versus dual antiplatelet therapy (DAPT) following LAAO.

A comprehensive search of PubMed, Scopus, Cochrane, and Web of Science was conducted in August 2024. Studies comparing low-dose DOACs and DAPT post-LAAO were included. The primary outcomes were a composite efficacy endpoint (DRT, strokes, and systemic embolism [SE]) and major bleeding events as the safety endpoint. Secondary outcomes included all bleeding events, all-cause mortality, and a composite of efficacy and safety endpoints.

Four studies with 727 patients were included. Low-dose DOACs were associated with lower rates of the primary composite efficacy endpoint compared to DAPT (OR = 0.36; 95% CI [0.16, 0.85], p = 0.01). No significant difference in major bleeding events was observed (OR = 0.36; 95% CI [0.11, 1.18]; p = 0.091; I² = 0%). Compared to DAPT, low-dose DOACs were also associated with lower rates of DRT events (OR = 0.36; 95% CI [0.16, 0.79], p = 0.011).

Low-dose DOACs effectively reduce thromboembolic events post-LAAO without increasing bleeding risk. These findings support their use as a viable ATT option, but larger trials are needed to confirm optimal regimens.

Atrial fibrillation (AF) is a relatively prevalent arrhythmia in patients with kidney failure requiring dialysis who face a high risk of stroke and bleeding and for whom anticoagulation is a challenging decision. Although direct oral anticoagulants (DOACs) may offer advantages over vitamin K antagonists (VKAs), their use in this patient profile remains unclear.

We conducted a systematic review and meta-analysis to compare DOACs and VKAs in patients with AF undergoing dialysis.

PubMed, Embase, and Cochrane Central databases were analyzed. The outcomes analyzed were total stroke (a composite of ischemic and hemorrhagic stroke), ischemic stroke, all-cause death, cardiovascular death, myocardial infarction, major bleeding, clinically relevant nonmajor bleeding and gastrointestinal bleeding. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random effects model. R software version 4.3.2 R Studio for Statistical Computing, Vienna, Austria) was used for statistical analyses. Heterogeneity was assessed with I2 statistics.

The final analysis included 486 patients from 4 randomized controlled trial studies. The median follow-up ranged from 5.8 to 18 months. Although a reduction in total stroke was observed in the group receiving DOACs (RR 0.40; 95% CI 0.17-0.92; P = .031; I2 = 0%), no significant difference was found between the groups for ischemic stroke (RR 0.42; 95% CI 0.17-1.04; P = .062; I2 = 0%). In addition, a statistically significant reduction in major bleeding was noted in the DOAC group (RR 0.64; 95% CI 0.41-0.98; P = .044; I2 = 0%). However, no significant differences were observed among the groups for all-cause death (RR 0.88; 95% CI 0.57-1.35; P = .567; I2 = 47%), cardiovascular death (RR 1.13; 95% CI 0.60-2.10; P = .700; I2 = 0%), or clinically relevant nonmajor bleeding (RR 1.11; 95% CI 0.67-1.84; P = .669; I2 = 0%).

In this meta-analysis, DOACs were associated with a lower risk of total stroke and major bleeding. However, DOACs and VKA groups exhibited similar rates of ischemic stroke, all-cause and cardiovascular death, clinically relevant nonmajor bleeding, and gastrointestinal bleeding.

The Thai Food and Drug Administration (TFDA) has approved direct oral anticoagulant (DOAC) dosing based on estimated creatinine clearance, eCrCl (Cockcroft-Gault equation). However, other renal function equations are often used in practice for patients with kidney disease, leading to potential discrepancies in DOAC dosing recommendations. The actual DOAC dosing patterns in resource-limited countries remain underreported. This cross-sectional study included patients with renal impairment who were treated at the outpatient department of Siriraj Hospital, Mahidol University, Thailand. Patients received their first DOAC for atrial fibrillation from January 2019 to December 2022. The primary objective was to evaluate the percentage of DOAC prescriptions compliant with TFDA guidelines using eCrCl. We also examined dosing agreement when substituting estimated glomerular filtration rate, eGFR (CKD-EPI) for eCrCl. Patient factors and the incidence of stroke and bleeding over a one-year follow-up were also assessed. A total of 326 patients and 1587 DOAC prescriptions were analyzed. The mean patient age was 79.1 ± 9.2 years, with a mean eGFR of 45.6 ± 9.9 mL/min/1.73 m2. TFDA-compliant dosing was observed in 68.2% of prescriptions. Dose disagreement between eGFR and eCrCl was 45%, with a trend toward overdosing using eGFR. An eGFR of less than 45 mL/min/1.73 m2 was associated with dose discrepancies. Stroke and bleeding incidences were low, with no differences across DOAC types. While most Thai patients received appropriate DOAC dosing, one-third did not comply with TFDA guidelines. Using eGFR instead of eCrCl may result in dosing differences, particularly in moderate to severe renal impairment.

Direct oral anticoagulants (DOACs) at reduced dosage regimens are the first choice of ischaemic stroke (IS) prevention for patients with atrial fibrillation (AF) and elevated bleeding risk or renal insufficiency. We compared the outcomes of reduced dose DOACs and warfarin.

We included all new-onset patients with AF in Finland from 2011 to 2018. Adjusted hazard ratios (HRs) for IS, intracranial haemorrhage (ICH), bleeding, and mortality were calculated for dabigatran (n = 2 672), rivaroxaban (n = 1 866), apixaban (n = 3 936), and warfarin (n = 43 548). Patients on warfarin were grouped into quartiles by their individual time-in-therapeutic range (TTR), with the second best TTR quartile as a reference group for comparisons. Risk of IS was highest in the low TTR quartiles of warfarin, lowest in the best TTR quartile (0.65 95% confidence interval, 0.51-0.83), and did not differ for dabigatran, rivaroxaban, and apixaban compared with the second best TTR quartile. Risk of ICH was highest in low TTR quartiles of warfarin (HRs 7.20, 5.48-9.46 and 1.91, 1.44-2.55), and was not different in patients on dabigatran, rivaroxaban, and apixaban. Risk of all-cause death and bleeding were lowest in the two best TTR quartiles, and highest in the poorest TTR group. Mortality was higher for dabigatran, rivaroxaban, and apixaban, compared with the second best TTR quartile of warfarin.

DOACs with reduced doses are efficient and safe stroke prevention therapy in high-risk patients with AF when compared with warfarin therapy of sufficient TTR. In this comparison, warfarin therapy of excellent TTR-quality was associated with the lowest risk of bleeding and mortality.

Among very older patients with atrial fibrillation (AF), the frequency of inappropriate direct oral anticoagulant (DOAC) dosing, associated factors, and temporal trends in practice are unknown.This retrospective study included consecutive inpatients aged 80 years or older with a discharge diagnosis of atrial fibrillation who were prescribed DOACs at discharge from Beijing Hospital between January 2018 and August 2023. Patients were stratified into underdosed, overdosed, or recommended dosing groups. Logistic regression analysis was performed to identify risk factors associated with inappropriate dosing, and temporal trends were evaluated using the Cochran-Mantel-Haenszel test.Among 676 inpatients aged ≥ 80 years with AF (mean age 84.4 ± 3.5 years; 53.1% female) who were prescribed a DOAC at hospital discharge (22.9% dabigatran, 62.3% rivaroxaban, 14.8% edoxaban), recommended dosing was observed in 338 patients (50.6%), underdosing in 308 (45.6%), and overdosing in 30 (4.4%). The overall rate of inappropriate dosing was 49.4%. Factors independently associated with underdosing included advanced age (OR = 1.98, 95% CI: 1.52-2.60, p < 0.001), lower creatinine clearance (OR = 0.98, 95% CI: 0.97-0.99, p = 0.01), and discharge from non-internal medicine wards (OR = 2.15, 95% CI: 1.33-3.45, p = 0.002). Overdosing was associated with younger age (OR = 0.38, 95% CI: 0.19-0.75, p = 0.005). Although the proportion of recommended dosing increased over the study period, and inappropriate dosing showed a declining trend, these changes did not reach statistical significance.Inappropriate DOAC dosing, especially underdosing, remains common in very older AF inpatients. This issue persists despite years passing, emphasizing the need for patient-focused, collaborative AF management and thorough prognostic studies.

Treatment with a low-dose non-vitamin K antagonist oral anticoagulant (NOAC) is common among hospitalized patients, and a model to predict the need for such treatment would support individualized interventions. This study evaluated the prevalence of low-dose edoxaban treatment and developed and evaluated a model to predict low-dose administration of edoxaban among hospitalized patients.

This study included 1208 inpatients with non-valvular atrial fibrillation (NVAF) or venous thromboembolism (VTE) who were treated with edoxaban. Univariate and multivariate analyses identified variables significantly associated with low-dose edoxaban therapy. Least absolute shrinkage and selection operator (LASSO) regression was used for data dimension reduction and selection of the best variables. A nomogram was built based on the predictive variables for easy visualization. Model performance was evaluated, and the model was further validated internally with 1000 bootstrap resamples.

The prevalence of low-dosing edoxaban treatment was 65.98% (797/1208). The predictors of edoxaban included in the final nomogram were age, weight, surgery or operation, anticoagulation indication, the use of antiarrhythmic drugs, anemia, and bleeding history. The model showed good discrimination with an area under the curve value of 0.792. The Hosmer‒Lemeshow test showed that the model had satisfactory goodness of fit (χ2 = 10.757, P = 0.2158). The calibration curve showed good agreement between predicted and actual probabilities.

The developed predictive model for low-dose edoxaban use among hospitalized patients was built using seven readily available variables and showed good performance. This study provides an empirical basis for early detection and intervention using a low-dose NOAC.

Patients with atrial fibrillation and a history of intracranial hemorrhage (ICH) face a dilemma when resuming anticoagulation therapy due to the risk of ICH recurrence versus the need for Ischemic stroke (IS) prevention. This study aims to evaluate the safety and efficacy of direct oral anticoagulants (DOAC) compared to no therapy or antiplatelets in these patients.

We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines. Electronic searches were performed in multiple databases (Cochrane, PubMed, Web of Science, Embase, Google Scholar, Scopus) up to March 1, 2024. We included randomized controlled trials (RCTs) and controlled clinical trials (CCTs) involving patients with atrial fibrillation and prior ICH. Studies compared the group with no therapy or antiplatelets (no-DOAC group). Outcomes assessed included mortality, IS, ICH recurrence, and major bleeding events.

Fifteen studies (8,318 patients) met the inclusion criteria, including 2,226 patients in the DOAC group and 5,936 in the no-OAC group. The major cardiovascular ischemic event was significantly lower in the DOAC group [OR = 0.11; CI 95% (0.03, 0.45); p = 0.002]. Ischemic stroke was lower in the DOAC group [OR = 0.53, 95% CI (0.39-0.72), p < 0.001]. There was no difference in ICH recurrence [OR = 1.25, 95% CI (0.28-5.71), p = 0.77] or major bleeding [OR = 0.63, 95% CI (0.23-1.72), p = 0.36]. Mortality rates were similar between groups [OR = 0.75, 95% CI (0.50-1.11), p = 0.15], while Heterogeneity was low for most outcomes.

DOACs appear to reduce the risk of IS without increasing mortality or major bleeding in patients with atrial fibrillation and prior ICH. However, the risk of ICH recurrence remains uncertain. These findings suggest a potential role for DOACs in this high-risk population, but further RCTs are needed to confirm these results.

Identifier CRD42024587511.

Direct oral anticoagulants (DOACs) have emerged as a preferred alternative to vitamin K antagonists (VKAs) for the prevention and treatment of thromboembolic disorders, offering improved safety, predictable pharmacokinetics, and ease of administration. Despite these advantages, their use in complex clinical scenarios presents significant challenges that necessitate individualized therapeutic strategies. This comprehensive review explores the efficacy, safety, and limitations of DOAC therapy in special populations, including patients with renal or hepatic impairment, obesity, cancer-associated thrombosis, and antiphospholipid syndrome. Additionally, we examine their role in uncommon thrombotic conditions such as superficial venous thrombosis, embolic stroke of undetermined source, upper extremity vein thrombosis, inferior vena cava thrombosis, pelvic vein thrombosis, and cerebral vein thrombosis. The pharmacokinetic variability of DOACs in renal and hepatic dysfunction requires caution to balance the bleeding and thrombotic risks. In obesity, altered drug distribution and metabolism raise concerns regarding appropriate dosing and therapeutic efficacy. Cancer-associated thrombosis presents a complex interplay of prothrombotic mechanisms, necessitating careful selection of anticoagulant therapy. Furthermore, the use of DOACs in antiphospholipid syndrome remains controversial due to concerns about recurrent thrombotic events. Finally, in some unusual scenarios like inferior vena cava, pelvic vein, and cerebral vein thrombosis, the use of DOACs has scarce evidence. This review aims to guide clinicians in optimizing anticoagulation management in challenging patient populations by synthesizing current evidence and providing practical recommendations.

Rivaroxaban, a Non-vitamin K oral anticoagulant (NOAC), is extensively employed for patients at heightened risk of thrombosis, including those with non-valvular atrial fibrillation (NVAF) and venous thromboembolism (VTE). However, to date, there is a lack of robust clinical data to explore the efficacy and safety of rivaroxaban in thromboprophylaxis during the early postoperative period (<6 months) in patients following surgical bioprosthetic valve (BPV).

The REVERSE trial is a prospective, multicenter, non-inferior, randomized controlled trial enrolling a planned 250 patients in China. Patients are randomly assigned 1:1 to receive rivaroxaban (20 mg once daily) or dose-adjusted warfarin (target international normalized ratio 2.0-3.0) for 6 months. The primary outcome is defined as the composite of all-cause death, major cardiovascular events, or major bleeding. The safety outcome is all bleeding events defined by the International Society on Thrombosis and Haemostasis (ISTH).

The REVERSE trial stands as the inaugural multicenter study dedicated to evaluating the efficacy and safety of rivaroxaban for early postoperative anticoagulation in BPV surgery patients. Its findings are anticipated to contribute pivotal evidence regarding the clinical advantages of NOACs.

URL: https://www.

gov; Unique identifier: NCT06476301.

Atrial fibrillation (AF), the most common cardiac arrhythmia globally, contributes significantly to morbidity and mortality. With advancements in implantable devices like pacemakers, defibrillators, and loop recorders, incidental detection of AF as device-detected AF (DDAF) or subclinical AF (SCAF) has become common. This asymptomatic AF presents unique management challenges, particularly in anticoagulation decisions for stroke prevention. Evidence from recent trials, notably NOAH-AFNET 6 and ARTESiA, indicates a complex risk-benefit profile for anticoagulation in DDAF. In ARTESiA, anticoagulation modestly reduced stroke and systemic embolism rates, though this effect did not reach statistical significance. The NOAH-AFNET 6 trial found no significant reduction in a composite of cardiovascular death, stroke, or systemic embolism with anticoagulation compared to placebo. Both trials revealed an increased bleeding risk, underscoring the need to carefully weigh stroke prevention against bleeding risks in DDAF. The 2024 European Society of Cardiology guidelines reflect this nuanced approach by advocating a tailored, risk-based strategy. Emerging evidence also shows that AF burden impacts heart failure (HF) outcomes, with a five-fold increase in HF hospitalizations associated with higher AF burden. This highlights the importance of rhythm or rate control to reduce HF progression, particularly in patients with both AF and HF, where reducing AF burden is associated with better prognosis and fewer hospitalizations. Future research should focus on refining anticoagulation strategies, especially for patients with low AF burden, and exploring novel approaches like intermittent anticoagulation and advanced monitoring to support personalized DDAF management.

Pregabalin, gabapentin, and carbamazepine, a potent inducer of cytochrome P450 (CYP) 3A4 and P-glycoprotein, are frequently used antiepileptic drugs that are often administered together with factor Xa inhibitors (FXaI). We aimed to investigate whether potentially clinically relevant drug-drug interactions occur with these combinations.

In an open-label fixed-sequence trial in 36 healthy volunteers, we evaluated the pharmacokinetics of 60 mg edoxaban and of a microdosed FXaI cocktail (25 µg apixaban, 50 µg edoxaban, and 25 µg rivaroxaban) before and during treatment with carbamazepine (12 evaluable volunteers, individually dosed to therapeutic concentrations), gabapentin (11 volunteers, titrated to 3 × 400 mg/d), and pregabalin (12 volunteers, titrated to 2 × 300 mg/d). The antiepileptics were dosed to steady-state and the CYP3A activity was evaluated by assessing the pharmacokinetics of microdosed midazolam (30 µg).

Carbamazepine reduced the area under the plasma concentration-time curve (AUC ∞ ) of 60 mg edoxaban by a factor of 0.48 (geometric mean ratio (GMR) with 90% CI (0.41-0.56); p < 0.0001) and Cmax by a factor of 0.47 (0.34-0.66) and reduced the exposure of the edoxaban metabolite M-4 to a similar extent. Carbamazepine also decreased the exposure (AUC ∞ ) of microdosed apixaban, edoxaban, and rivaroxaban by a factor of 0.66, 0.59, and 0.56, respectively. Gabapentin and pregabalin did neither affect the exposure of 60 mg edoxaban nor the exposure of any microdosed FXaI.

Carbamazepine decreased FXaI exposure to a clinically relevant extent and dose adjustment may be required to maintain an adequate anticoagulant effect, whereas gabapentin and pregabalin do not require dose adjustment of FXaI.

Direct oral anticoagulants (DOACs) are commonly used to prevent and treat thromboembolic diseases. This study aimed to assess and compare dementia related adverse events (AEs) associated with DOACs.

AEs related to DOACs from January 2014 to June 2023 were extracted from the FDA Adverse Event Reporting System (FAERS) database. Disproportionality analysis methods, including reporting odds ratio (ROR), proportional reporting ratio, Bayesian Confidence Propagation Neural Network, and Multi-Item Gamma Poisson Shrinker, were used to evaluate the association between DOACs and dementia-related AEs.

There were 12,692,968 AEs reported in FAERS after deduplication. Among these, 165, 206, 1574, and 12 dementia-related AEs that were attributed to dabigatran, rivaroxaban, apixaban, and edoxaban, respectively. Apixaban showed the strongest association with dementia-related AEs (ROR 7.66, 95% confidence interval (CI) 7.27-8.06), while rivaroxaban had the lowest ROR (0.95, 95%CI 0.83-1.09). Women exhibited higher RORs for all DOACs, with apixaban showing the most significant correlation. Subgroup analysis indicated a significant link between apixaban and dementia, dementia Alzheimer's type and senile dementia.

Apixaban appears most associated with dementia-related AEs among DOACs, whereas rivaroxaban poses a lower risk. Further research is needed to validate these findings through large-scale prospective studies.