Stroke Prevention In Atrial Fibrillation Research Articles

Stroke prevention in atrial fibrillation : The ARTESIA study in the light of current knowledge

Stroke prevention in atrial fibrillation : The ARTESIA study in the light of current knowledge

Safety of DOACs in patients with Child-Pugh Class C cirrhosis and trial fibrillation.

Anticoagulation (AC) is used for stroke prevention in atrial fibrillation (AF). Direct Oral Anticoagulants (DOACs) are safe in patients with AF without cirrhosis, they are hardly studied in patients with advanced cirrhosis. Our study evaluates the safety and outcomes of DOACs in patients with Child-Pugh class C cirrhosis (CPC). We queried TriNetX Database. Patients with CPC and AF were divided into three cohorts: patients on DOACs, no AC, and warfarin. Three study arms were created using a 1:1 propensity score matching system (PSM). Totally 16 029 patients met the inclusion criteria. Of those, 20.2% (n = 3235) were on DOACs, 47.1% (n = 7552) were not on AC, and 32.7% (n = 5242) were on warfarin. First arm comparing AC versus no AC, a statistically significant benefit was identified in 3-year mortality risk (47% vs 71%, P < 0.0001) and transplant status (17% vs 5%, p < 0.0001) with AC. However, no significant difference was identified regarding intracranial hemorrhage and GI bleeding risk. Second arm comparing patients on DOACs versus no AC, we identified mortality benefit (40% vs 72%, P < 0.0001) and a higher transplant rate (9% vs 3.2%, P < 0.0001) with DOACs. Intracranial hemorrhage rates (6% vs 4%, P = 0.03) were higher in patients on DOACs. Third arm comparing patients on DOACs versus Warfarin, a statistically significant lower risk of intracranial hemorrhage (6.6% vs 8.7%, P = 0.004) and GI bleed (2% vs 2.4%, P < 0.0001) were identified in patients on DOACs. Anticoagulation is safe in patients with CPC with AF and may provide a mortality benefit. DOACs are a safer alternative to warfarin.

Acute severe renal failure in a patient receiving apixaban: a case report

Because there is little clinical experience with apixaban in patients with severe renal impairment and non-valvular atrial fibrillation, the European Medicines Agency does not advise using it to prevent strokes in these patients. However, only a small number of pharmacokinetic and pharmacodynamic investigations showed how crucially different elimination pathways contribute to the clearance of apixaban. A 74-year-old male patient who was receiving apixaban treatment for stroke prevention in atrial fibrillation was referred to our hospital because of acute severe renal failure brought on by dehydration and abnormally elevated apixaban plasma levels. The patient was treated only with intravenous fluid therapy; serum creatinine recovered slowly over the course of six days, but plasma apixaban levels recovered quickly. No bleeding events have been recorded. Our experience demonstrates the safety profile of apixaban in cases of severe renal failure, but it also emphasizes the need for more research to confirm this evidence.

[Antithrombotic therapy in acute coronary syndrome].

Dual antiplatelet therapy (DAPT) is the cornerstone of maintenance medication following acute coronary syndromes (ST elevation myocardial infarction, non-ST elevation myocardial infarction, unstable angina). Over the last decade, P2Y12 inhibition in addition to low-dose acetylsalicylic acid has been intensively debated. In patients with acute coronary syndromes, balancing the reduction in cardiovascular events and increase in major bleeding during treatment with more potent P2Y12 inhibitors such as prasugrel and ticagrelor is still an issue. A special focus is on patients already treated with oral anticoagulants for stroke prevention in atrial fibrillation who require additional platelet inhibition following coronary stenting. This article summarizes the major recommendations given in the most recent Guideline for "Acute Coronary Syndromes" published by the European Society of Cardiology (ESC). The recommendations finally address strategies to reduce an increased bleeding risk based on clinical predictors.

Drug-Drug Interactions of FXI Inhibitors: Clinical Relevance.

Inhibitors of the factor FXI represent a new class of anticoagulant agents that are facing clinical approval for the treatment of acute coronary syndrome (ACS), venous thromboembolism (VTE), and stroke prevention of atrial fibrillation (AF). These new inhibitors include chemical small molecules (asundexian and milvexian), monoclonal antibodies (abelacimab, osocimab, and xisomab), and antisense oligonucleotides (IONIS-FXIRX and fesomersen), and thus, they have very peculiar and different pharmacokinetic and pharmacodynamic properties. Besides their clinical efficacy and safety, based on their pharmacological heterogeneity, the use of these drugs in patients with comorbidities may undergo drug-drug interactions (DDIs) with other concomitant therapies. Although only little clinical evidence is available, it is possible to predict clinically relevant DDI by taking into consideration their pharmacokinetic properties, such as the CYP450-dependent metabolism, the interaction with drug transporters, and/or the route of elimination. These characteristics may be useful to differentiate their use with the direct oral anticoagulant (DOAC) anti -FXa (rivaroxaban, apixaban, edoxaban) and thrombin (dabigatran), whose pharmacokinetics are strongly dependent from P-gp inhibitors/inducers. In the present review, we summarize the current clinical evidence on DDIs of new anti FXI with CYP450/P-gp inhibitors and inducers and indicate potential differences with DOAC anti FXa.

Stroke prevention in atrial fibrillation with chronic kidney disease: a delicate balance of efficacy and safety considerations

Stroke prevention in atrial fibrillation with chronic kidney disease: a delicate balance of efficacy and safety considerations

FactorXI Inhibitors: A New Horizon in Anticoagulation Therapy.

Anticoagulation therapy has undergone significant evolution, marked by the emergence of direct oral anticoagulants with distinct advantages. Despite these advancements, challenges persist in managing residual thrombotic and bleeding risks, particularly among vulnerable populations. The pursuit of alternative drugs has honed in on factorXI/XIa inhibitors. This comprehensive review delves into several key aspects regarding this new target: (i) the role of factorXI in the coagulation cascade; (ii) the genetic evidence and pathophysiologic rationale supporting factorXI inhibition as a therapeutic target; (iii) an exploration of the various types of factorXI/XIa inhibitors currently under investigation; (iv) potential applications of these medications, spanning thromboprophylaxis after orthopedic surgery, stroke prevention in atrial fibrillation, secondary prevention after acute coronary syndrome, non-cardioembolic stroke, thromboprophylaxis after foreign material implantation, end-stage renal disease, and patients with cancer; and (v) an overview of ongoing studies, recent findings, and the future trajectory of research into these drugs.

Edoxaban for stroke prevention in atrial fibrillation and factors associated with dosing: patient characteristics from the prospective observational ETNA-AF-China registry

Real-world data on effectiveness and safety of a single non-vitamin K antagonist oral anticoagulant in the Chinese population with atrial fibrillation (AF) are limited. This study reports characteristics of patients treated with edoxaban and factors associated with dosing patterns from routine care in China. ETNA-AF-China (NCT04747496) is a multicentre, prospective, observational study enrolling edoxaban-treated patients from four economic regions with a targeted 2-year follow-up. Of the 4930 patients with AF (mean age: 70.2 ± 9.5 years; male, 57.1%), the mean creatinine clearance (CrCl), CHA2DS2-VASc, and HAS-BLED scores were 71.2 mL/min, 2.9, and 1.6. Overall, 6.4% of patients were perceived as frail by investigators. Available label dose reduction criteria (N = 4232) revealed that 3278 (77.5%) patients received recommended doses and 954 (22.5%) non-recommended doses. Northeast (53.0%) and West (43.1%) regions had the highest prescriptions of 60 mg and 30 mg recommended doses, respectively. Non-recommended 30 mg doses were more frequently prescribed in patients with antiplatelet use and history of heart failure than recommended 60 mg. Multivariate analysis identified advanced age as the strongest associated factor with non-recommended doses. Frailty had the strongest association with 30 mg except for age, and history of TIA was the most relevant factor associated with 60 mg. In conclusion, patients in the ETNA-AF-China study were predominantly aged 65 years and older, had mild-to-moderate renal impairment and good label adherence. Advanced age was associated with non-recommended doses, with frailty most common for non-recommended 30 mg and a history of TIA for the non-recommended 60 mg dose.

Comparative safety and effectiveness of reduced doses of direct acting oral anticoagulants for stroke prevention in atrial fibrillation.

This Nordic observational cohort study aims to assess the effectiveness and safety of reduced-dose direct-acting oral anticoagulants (DOACs) dabigatran, rivaroxaban, and apixaban compared to standard warfarin for stroke prevention in non-valvular atrial fibrillation. The study, utilizing nationwide administrative databases from Denmark, Sweden, Norway, and Finland, spanned from January 1, 2011, to December 31, 2018 (2017 for Sweden). The cohort included 26,883 patients initiating reduced-dose DOACs and 108,014 comparable warfarin patients. Effectiveness was measured by the composite endpoint of ischemic stroke and systemic embolism, while safety was assessed through intracranial hemorrhage. The meta-analysis across countries revealed similar or lower incidences of ischemic stroke and systemic embolism in patients on reduced-dose DOACs compared to standard warfarin (rivaroxaban: HR 0.93, dabigatran: HR 0.88, apixaban: HR 0.79). Incidences within warfarin groups ranged from 2.16 to 3.71 per 100 person-years, comparable to DOAC recipients. Intracranial hemorrhage rates were generally low, ranging from 0.16 to 1.85 per 100 person-years. In comparison with warfarin patients, meta-analyses yielded HRs for rivaroxaban (1.41), dabigatran (0.35), and apixaban (0.72). In this study, atrial fibrillation patients initiating reduced-dose rivaroxaban and dabigatran exhibited incidences of ischemic stroke and systemic embolism similar to warfarin, and for apixaban, even lower. Rates of intracranial hemorrhage were comparable to or lower for patients on DOACs compared to warfarin.

Abstract 66: Optimal Delay Time to Initiate Anticoagulation After Ischemic Stroke in Atrial Fibrillation: Primary Results of the START Trial

Introduction: Clinical practice guidelines recommend initiation of anticoagulation within 2 weeks after stroke due to atrial fibrillation (AF). It is unknown whether there is an optimal day within that 14-day period that balances the risks of recurrent embolic vs serious hemorrhagic events. Methodology: The Lone Start Stroke START trial is a pragmatic, prospective, multi-center, response-adaptive randomized Phase 2 study of 200 patients prescribed a direct oral anticoagulant (DOAC) for secondary prevention of stroke due to AF. Patients were randomized into one of 4 Arms: Day 3-4 from stroke onset, Day 6, Day 10, or Day 14. The primary outcome was an ischemic (stroke or systemic embolus) or hemorrhagic (ICH or major systemic hemorrhage) event observed within 30 days from the index stroke time of onset. Posterior probabilities that each arm was the best were calculated at predefined intervals and randomization allocations were adjusted to favor the Arms with higher probabilities. Results: The median age was 75 (IQR 65-81), median NIHSS at presentation was 7 (IQR 4-14), median lesion diameter was 3.1 cm (IQR 2.0-4.4) at the time of randomization. The sample was 50% female, 17.5% non-white, and 16.5% Hispanic. Apixaban was the prescribed DOAC in 89% of the patients. No ischemic events were observed for Arm 1, and no hemorrhage events were observed for Arm 4. Arm 1 (3-4 days) had a posterior 41.1% probability of being the best among the four, with probabilities of 26.4%, 17.1%, and 15.4 % respectively, for the other arms. Response adapted randomization was feasible and favored the earlier two arms. Expected event rates for each arm are presented in the Table. The timing and severity of the outcome events will be presented at the conference. Conclusion: Although the START trial did not identify a clearly superior day to initiate DOAC for secondary stroke prevention in AF, the evidence suggests that initiating DOAC early is better than at later times within the first 2 weeks after stroke onset.

Consensus on Stroke Prevention in Atrial Fibrillation and Utilization of NOACs in the Real-World Setting in India

Atrial fibrillation (AF) is the most frequent cardiac arrhythmia. Prevention of stroke and systemic thromboembolism remainsthe cornerstone of the management of AF. Even today, there are unresolved knowledge gaps in AF pathophysiology, screeningand therapeutic strategies and stroke prevention. The modified DELPHI method was used to develop the best practicerecommendations for the management of AF in a real-world setting with the participation of 500 cardiologists across India.The experts concurred that the decision to initiate antithrombotic treatment in patients with transient AF could be based onthe duration of transient AF, the co-existence of the risk factor for stroke and echocardiographic abnormalities impact thedecision. The decision to initiate anticoagulant therapy in device-detected atrial high-rate episodes (AHRE) can be decidedbased on the duration of AHRE, the burden of AHRE and the individual’s risk of stroke and thromboembolism. The benefitof early anticoagulation should be balanced with the risk of intracerebral hemorrhage (ICH), especially in elderly patientsand in severe strokes. Apixaban is the preferred drug in patients with concomitant ischemic heart disease (IHD), patientswith a history of gastrointestinal (GI) bleeding, patients with underlying malignancy, elderly patients with AF, patients withcomorbid diseases and patients with hepatic disease or renal disease. Apixaban was considered to be an affordable noveloral anticoagulant (NOAC) for Indian patients for primary and secondary stroke prophylaxis in AF patients

Efficacy and Safety of Different Dosing Regimens of Rivaroxaban in Patients With Atrial Fibrillation for Stroke Prevention: A Systematic Review and Meta-Analysis.

Atrial fibrillation (AF) poses a substantial risk of stroke, necessitating effective anticoagulation therapy. This systematic review and meta-analysis (SRMA) evaluates the efficacy and safety of different dosing regimens of rivaroxaban in patients with AF. A comprehensive search of relevant databases, focusing on studies published from 2017 onward, was conducted. Inclusion criteria comprised randomized controlled trials (RCTs) and observational studies comparing standard and reduced dosing of rivaroxaban in AF. Data extraction and risk of bias (ROB) assessment were performed, and a meta-analysis was conducted for relevant outcomes. A total of 21 studies fulfilled the inclusion criteria. Standard dosing demonstrates a slightly lower risk of composite effectiveness outcomes and safety outcomes (HR: 0.79, 95% CI: 0.66-0.94, P=0.01) compared to reduced dosing (HR: 0.83, 95% CI: 0.71-0.97, P=0.02). Notable differences in major bleeding, gastrointestinal bleeding (GIB), and intracranial bleeding favored standard dosing. Hemorrhagic stroke and all-cause stroke rates differed significantly, with standard dosing showing a more favorable profile for ischemic stroke prevention. This study highlights the pivotal role of personalized anticoagulation therapy in AF. Standard dosing of rivaroxaban emerges as a preferred strategy for stroke prevention, balancing efficacy and safety. Clinical decision-making should consider individual patient characteristics and future research should delve into specific subpopulations and long-term outcomes to further refine treatment guidelines. The study bridges evidence from clinical trials to real-world practice, offering insights into the evolving landscape of AF management.

Stroke Prevention in Atrial Fibrillation: Our Current Failures and Required Research.

Nonvalvular atrial fibrillation is a common rhythm disorder of middle-aged to older adults that can cause ischemic strokes and systemic embolism. Lifelong use of oral anticoagulants reduces the risk of these ischemic events but increases the risk of major and clinically relevant hemorrhages. These medications also require strict compliance for efficacy, and they have nontrivial failure rates in higher-risk patients. Left atrial appendage closure is a nonpharmacological method to prevent ischemic strokes in atrial fibrillation without the need for lifelong anticoagulant use, but this procedure has the potential for complications and residual embolic events. This workshop of the Roundtable of Academia and Industry for Stroke Prevention discussed future research needed to further decrease the ischemic and hemorrhagic risks among patients with atrial fibrillation. A direct thrombin inhibitor, factor Xa inhibitors, and left atrial appendage closure are FDA-approved approaches whereas factor XIa inhibitors are currently being studied in phase 3 randomized controlled trials for stroke prevention. The benefits, risks, and shortcomings of these treatments and future research required in different high-risk patient populations are reviewed in this consensus statement.

Patients on vitamin K treatment: is switching to direct-acting oral anticoagulation cost-effective? A target trial on a prospective cohort

AimsDirect-acting oral anticoagulants (DOACs) have, to a substantial degree, replaced vitamin K antagonists (VKA) as treatments for stroke prevention in atrial fibrillation (AF) patients. However, evidence on the real-world causal...

Appropriate Use of Anticoagulants among Nonvalvular Atrial Fibrillation Patients at a University Hospital in Thailand

OBJECTIVE: Warfarin is primarily used for stroke prevention in atrial fibrillation (AF) patients in Thailand. Novel oral anticoagulants (NOACs) are used less commonly due to their high cost. This study aimed to evaluate the appropriate use of anticoagulants and clinical outcomes among nonvalvular AF (NVAF) patients. METHODS: This retrospective study collected data from the electronic medical records of patients who were diagnosed with NVAF between January 2014 and December 2019 at the Faculty of Medicine, Vajira Hospital. Baseline characteristics, prescribed indication, types and doses of anticoagulant, and ischemic and hemorrhagic outcomes were recorded and analyzed. RESULTS: We analyzed 783 patients with NVAF in this study. Of these, 539 (68.90%) were treated with oral anticoagulants (OAC), including 344 patients (43.90%) with warfarin therapy and 195 (24.90%) with NOACs. Meanwhile, 492 (73.10%) patients with CHA2DS2VASC score ≥ 2 received OAC therapy that was suitable for their indication. Of the 344 patients who received warfarin, 112 patients (32.60%) had an optimal time in therapeutic range (TTR) level of ≥ 65%. Of the 195 NOAC patients, only 98 (50.30%) received appropriate doses of NOACs. There was no statistically significant difference in the overall incidence rates of ischemic stroke/systemic embolism, bleeding, cardiovascular death, and all-cause death between the warfarin and NOACS groups. Appropriate TTR levels in the warfarin group was associated with significantly lower incidence rates of cardiovascular death (hazard ratio: 0.14; 95% CI: 0.02–0.79; p = 0.02) and all-cause death (hazard ratio: 0.36; 95% CI: 0.12–0.87; p = 0.01), than inappropriate TTR levels. CONCLUSION: Most NVAF patients received oral anticoagulants with the appropriate indication. Warfarin is the most prescribed oral anticoagulant for patients with NVAF. About half of the patients received inappropriate doses of oral anticoagulants that potentially adversely affected the study outcomes of cardiovascular and all-cause deaths.

Selection of Non-vitamin K Antagonist Oral Anticoagulant for Stroke Prevention in Atrial Fibrillation Based on Patient Profile: Perspectives from Vietnamese Experts. Part 1.

In Asia, especially Vietnam, AF is a common arrhythmia and is linked to a higher risk of stroke and systemic embolism. Anticoagulation therapy for stroke prevention in AF patients can result in bleeding complications. To effectively manage AF, adopting appropriate anticoagulation and addressing modifiable risk factors are crucial. Vietnamese clinicians are particularly interested in non-vitamin K antagonist oral anticoagulants (NOACs), a recent development in AF treatment. However, the lack of head-to-head trials comparing NOACs makes selecting a specific NOAC challenging. This review aims to provide a comprehensive overview of the available clinical evidence on NOACs for stroke prevention in AF to assist clinicians in making informed decisions and improving treatment outcomes in patients with AF. The first part of this review will present the current landscape of AF in Vietnam, focusing on AF prevalence and highlighting gaps in clinical practice. Furthermore, this part extensively discusses the anticoagulation strategy for both primary and secondary stroke prevention in AF.

Selection of Non-vitamin K Antagonist Oral Anticoagulant for Stroke Prevention in Atrial Fibrillation Based on Patient Profile: Perspectives from Vietnamese Experts. Part 2.

Part 1 of this review provided an overview of AF in Vietnam, with a particular focus on primary and secondary stroke prevention. Part 2 explores the management of AF in special, high-risk and clinically common patient populations, including those with renal impairment, diabetes, the elderly, and those with coronary artery disease. Furthermore, Part 2 addresses the challenges posed by patients with AF who have a bioprosthetic valve, a group situated in a grey area of consideration. Managing AF in these patient groups presents unique clinical challenges that require careful consideration. Physicians are tasked with addressing specific clinical questions to identify the optimal anticoagulation strategy for each individual. To inform these decisions, subgroup analyses from pivotal studies are presented alongside real-world data derived from clinical practice. By synthesising available information and considering the nuanced clinical context, the aim is to provide informed perspectives that align with current medical knowledge and contribute to the enhancement of patient care in these challenging scenarios.

Risk scores for major bleeding from direct oral anticoagulants: comparing predictive performance in patients with atrial fibrillation

BackgroundDespite direct oral anticoagulants (DOACs) being safer than warfarin for stroke prevention in atrial fibrillation (AF), major bleeding concerns persist. Most bleeding risk scores predate DOAC approval. ObjectivesThis study aimed to compare the Age, history of Bleeding, and non-bleeding related Hospitalisation [ABH] score’s performance—derived for DOAC-treated patients—with those of 5 other scores (Anticoagulation and Risk Factors in Atrial Fibrillation [ATRIA], Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly [>65 years], Drugs/alcohol concomitantly [HAS-BLED], Hepatic, Hepatic or Renal Disease, Ethanol Abuse, Malignancy, Older Age, Reduced Platelet Count or Function, Re-Bleeding, Hypertension, Anemia, Genetic Factors, Excessive Fall Risk and Stroke [HEMORR2HAGES], Outcomes Registry for Better Informed Treatment of Atrial Fibrillation [ORBIT-AF], and Congestive heart failure, Hypertension, Age ≥75 [doubled], Diabetes, Stroke [doubled]-Vascular disease, Age 65–74, Sex category [CHA2DS2-VASc]) in predicting DOAC-related major bleeding in patients with AF. MethodsIn this retrospective study of 2364 patients with nonvalvular AF on rivaroxaban or apixaban (median age, 68.3 years; 32.1% women), International Society on Thrombosis and Haemostasis–defined major bleeding (incidence, 4.1%; n = 97) was analyzed. C-statistics from time-dependent receiver operating characteristic (ROC) curves for continuous risk scores were the primary comparison metric, but other metrics, such as decision curves, were also compared. ResultsAt 100 days, C-statistics were highest for ORBIT-AF and ATRIA (0.62 and 0.61, respectively, with other scores having an area under the ROC curve of <0.60); some significant differences favored ORBIT-AF. At 1100 days, C-statistics remained highest for ORBIT-AF and ATRIA (0.62 and 0.61, respectively, with other scores having an area under the ROC curve of <0.60 again), and ORBIT-AF had significantly higher C-statistics than those for all other risk scores (P < .05), except for ATRIA. At 2100 days, all C-statistics were <0.60 with no significant differences. Decision curves showed the greatest net benefit for ORBIT-AF and ATRIA at 100 days and for ATRIA at 1100 days, with no discernible net benefit for any of the scores at 2100 days. ConclusionORBIT-AF and ATRIA provided the best bleeding risk prediction within the first 1100 days. None of the 6 bleeding risk scores provided predictive benefit over 2100 days of DOAC treatment.

Tolerability of Direct Oral Anticoagulants and Low Molecular Weight Heparin in Patients with Brain Tumors or CNS Metastases

Background: Despite the increase in the use of direct oral anticoagulants (DOACs) for cancer-associated thrombosis, limited data exists regarding the safety of DOACs in patients with brain metastases or primary brain tumors. The purpose of this retrospective cohort study is to describe overall tolerability of DOACs compared to low-molecular weight heparin (LMWH) for the treatment of venous thromboembolism (VTE) or for stroke prevention in atrial fibrillation (AF), in patients with brain tumors or CNS metastases. Methods: This is a single center, institutional review board approved retrospective cohort study at New York University Langone Health of patients with primary brain tumors or CNS metastasis that received therapeutic dosed anticoagulation with either a DOAC or LMWH (enoxaparin) between December 1, 2018 and August 19, 2022. Electronic medical records were reviewed for pertinent data. The primary outcome was tolerability of anticoagulation, which included continuation of initial anticoagulation therapy and absence of any switches in anticoagulation, dose adjustments or temporary interruptions. Reasons for discontinuations included bleeding events, intolerance/patient preference (such as the need for subcutaneous administration or cost of therapy), provider preference, or a change in clinical status such as transition to hospice or unable to determine based on chart review. Secondary outcomes included the incidence of anticoagulation discontinuations secondary to an intracerebral hemorrhage (ICH). Results: A total of 153 patients were included (DOAC n = 105, 69%; enoxaparin n = 48, 31%). The study population was predominantly White (74%), male (59%), with a median BMI≥30 kg/m2 in 40% of the cohort and age of 65 (IQR 56-73) years; however, the enoxaparin group was younger than the DOAC group at 59.5 years vs. 67 years (p &amp;lt;0.001), respectively at the time of anticoagulation initiation. Primary brain tumors were the most prevalent in the total cohort at 89%, with enoxaparin most commonly prescribed at 71% versus a DOAC at 47%, p = 0.005. Other primary malignancies included anaplastic astrocytoma, glioma, anaplastic oligodendroglioma, and tanycytic ependymoma. Non-small cell lung cancer was the most common malignancy that resulted in CNS metastasis (7.2%). The most common indication for anticoagulation was for the treatment of VTE at 70%, followed by stroke prevention in AF at 28%, with the remainder 2% as off-label. The primary outcome of remaining on initial anticoagulant chosen without any anticoagulant therapy changes occurred in only 52% of the cohort. There were more changes in therapy in the enoxaparin cohort at 29, 60% vs. 44, 42% for the DOAC cohort, p = 0.033, driven by provider preference in 48% of the cohort and patient intolerance in 29% of the cohort. More patients in the enoxaparin cohort were switched to a DOAC (n = 17) and more patients in the DOAC cohort had their initial anticoagulation discontinued for non- ICH reasons (n = 14). The median time to any anticoagulation switch was 2.12 months (IQR 0.35-4.27 months). Discontinuations in patients who were still alive was primarily driven by completion of therapy, deemed by the treatment team, intolerance or patient preference, and provider preference (Table 1). Though the reason for provider preference was not always clearly elucidated upon chart review, this trend supports the movement towards increasing DOAC use. The secondary outcome of the incidence of ICH was also lower in the DOAC cohort compared to enoxaparin at 3.8 vs 14.6% (p = 0.037). (Figure 1) Conclusions: Our study demonstrates real world prescribing practice of anticoagulants for the treatment of VTE or stroke prevention in AF in patients with primary brain tumors or metastases. Although initial anticoagulants chosen were either discontinued or switched to an alternative agent, we observed a shift towards a preference for DOACs, similar to the shift towards DOACs for cancer associated thrombosis. We also observed a lower incidence of ICH with DOACs compared to LMWH. However, these results should be confirmed in a randomized controlled trial to account for the inherent selection biases we could not account for, which may have favored the initial anticoagulant chosen, the reason for switch, and overall tolerability.

Apixaban Vs Vitamin K Antagonist As Anticoagulant Therapy in Patients with End-Stage Kidney Disease on Hemodialysis and with Atrial Fibrillation

BACKGROUND Evidence of net safety and benefit of anticoagulation for stroke prevention in patients with end-stage kidney disease (ESKD) on hemodialysis and with atrial fibrillation (AF) is lacking because patients with advanced CKD and those with end-stage kidney disease (ESKD) have been excluded from randomized clinical trials of stroke prevention in AF. In Europe, apixaban is not approved for the indication of prevention of stroke and systemic embolism in adult patients with ESKD on hemodialysis and AF. AIM To assess the effectiveness and safety according to Apixaban or VKA treatment. The effectiveness outcome was defined by ischemic stroke, all-cause death and myocardial infarction. The safety outcome was defined by a first event of major bleeding, clinically relevant nonmajor bleeding, or all-cause death. METHODS Unicenter, observational and retrospective study. Data was collected between January 2018 and July 2022. We included adult patients with ESKD on hemodialysis and AF and a CHA2DS2-VASc score ≥2 treated with low dose of Apixaban (2.5 mg twice daily) or VKA from the beginning of treatment. Patients in the VKA group received Acenocoumarol. Demographic, laboratory data and clinical presentation of AF were collected. Patients had a minimum follow-up (FU) of 6 months. Apixaban plasma drug concentrations were measured during the FU (week 1 and month 3). Blood samples were draw just before the next dose (Ctrough) and at 2-3 hours (Cpeak) after of drug intake using the Technoclone anti-Xa assay from Technoclone (Vienna-Austria). Bleeding events were classified according to ISTH criteria. RESULTS A total of 302 patients with NVAF and ESKD on hemodialysis were included. Among all patients, 192 (63.5%) were treated with Apixaban and 110 VKA. Mean FU was 14.8 and 12.5 months (DOAC vs VKA; p:0.53). Demographic characteristics are summarised in table 1. In Apixaban group, 100% of patients received reduce-dose, according to the care protocol established in our center and showed predictable pharmacokinetic, Ctrough (94.5- 180 μg/L) and Cmax (150-419 μg/L). In VKA group, Time in therapeutic range (international normalized ratio, 2.0-3.0) for Acenocumarol treated patients was 42% (interquartile range, 19%-60%). Stroke or systemic embolism occurred in three patients in the Apixaban group (1.04 %/year) and seven patients in the VKA group (7.2 %/year) [DOAC vs LMWH; p&amp;lt;0.05]. The apixaban group experienced fewer overall bleeding events than the VKA group (17.3% vs 39.7%; P = .01); this significant difference persisted in adjusted analysis (OR = 0.13; 95% CI = 0.04-0.42; P = .001). Major bleeding events were less frequent in the apixaban group compared with patients on VKA (4.7% vs 25%; P = .01). There were no significant differences regarding in all-cause mortality, 18.8% versus 21.5% respectively. CONCLUSIONS Compared to VKA, our findings suggest that low dose of apixaban is a safe and effective alternative in patients with AF and ESKD on hemodialysisis and low dose of apixaban showed predictable pharmacokinetic.