Atrial Fibrillation, Thromboembolic Risk, and Anticoagulation in Cardiac Amyloidosis: A Review.

Cardiac amyloidosis (CA) is caused by extracellular myocardial deposition of amyloid fibrils that are primary derived either from misfolding of transthyretin (ATTR) or light-chain (AL) proteins. CA is associated with atrial fibrillation, potentiated by electromechanical changes as a result of amyloid infiltration in the myocardium. CA also predisposes to thromboembolism and could potentially simultaneously elevate bleeding risk. In this review, we aim to explore and compare the prevalence and pathophysiological mechanisms of atrial fibrillation and thromboembolism in ATTR and AL, examine bleeding risk and factors that promote bleeding, and compare anticoagulation strategies in CA. Finally, we highlight knowledge gaps in the field of thromboembolism in CA to guide future research.

Blood Markers of Inflammation, Neurodegeneration, and Cardiovascular Risk in Early Parkinson's Disease.

BACKGROUND: Recent studies point toward a significant impact of cardiovascular processes and inflammation on Parkinson's disease (PD) progression. OBJECTIVE: The aim of this study was to assess established markers of neuronal function, inflammation, and cardiovascular risk by high-throughput sandwich immune multiplex panels in deeply phenotyped PD. METHODS: Proximity Extension Assay technology on 273 markers was applied in plasma of 109 drug-naive at baseline (BL) patients with PD (BL, 2-, 4-, and 6-year follow-up [FU]) and 96 healthy control patients (HCs; 2- and 4-year FU) from the de novo Parkinson's cohort. BL plasma from 74 individuals (37 patients with PD, 37 healthy control patients) on the same platform from the Parkinson Progression Marker Initiative was used for independent validation. Correlation analysis of the identified markers and 6 years of clinical FU, including motor and cognitive progression, was evaluated. RESULTS: At BL, 35 plasma markers were differentially expressed in PD, showing downregulation of atherosclerotic risk markers, eg, E-selectin and ß2 -integrin. In contrast, we found a reduction of markers of the plasminogen activation system, eg, urokinase plasminogen activator. Neurospecific markers indicated increased levels of peripheral proteins of neurodegeneration and inflammation, such as fibroblast growth factor 21 and peptidase inhibitor 3. Several markers, including interleukin-6 and cystatin B, correlated with cognitive decline and progression of motor symptoms during FU. These findings were independently validated in the Parkinson Progression Marker Initiative. CONCLUSIONS: We identified and validated possible PD plasma biomarker candidates for state, fate, and disease progression, elucidating new molecular processes with reduced endothelial/atherosclerotic processes, increased thromboembolic risk, and neuroinflammation. Further investigations and validation in independent and larger longitudinal cohorts are needed. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Gaps in guideline-recommended anticoagulation in patients with atrial fibrillation and elevated thromboembolic risk within an integrated healthcare delivery system.

BACKGROUND: Atrial Fibrillation (AF) is the leading cause of stroke, which can be reduced by 70% with appropriate oral anticoagulation (OAC) therapy. Nationally, appropriate anticoagulation rates for patients with AF with elevated thromboembolic risk are as low as 50% even across the highest stroke risk cohorts. This study aims to evaluate the variability of appropriate anticoagulation rates among patients by sex, ethnicity, and socioeconomic status within the Kaiser Permanente Mid-Atlantic States (KPMAS). METHODS: This retrospective study investigated 9513 patients in KPMAS's AF registry with CHADS2 score ≥ 2 over a 6-month period in 2021. RESULTS: Appropriately anticoagulated patients had higher rates of diabetes, prior stroke, and congestive heart failure than patients who were not appropriately anticoagulated. There were no significant differences in anticoagulation rates between males and females (71.8% vs. 71.6%%, [OR] 1.01; 95% CI, 0.93-1.11; P = .76) nor by SES-SVI quartiles. There was a statistically significant difference between Black and White patients (70.8% vs. 73.1%, P = .03) and Asian and White patients (68.3% vs. 71.6%, P = .005). After adjusting for CHADS2, this difference persisted for Black and White participants with CHADS2 scores of ≤3 (62.6% vs. 70.6%, P < .001) and for Asian and White participants with CHADS2 scores > 5 (68.0% vs. 79.3%, P < .001). CONCLUSIONS: Black and Asian patients may have differing rates of appropriate anticoagulation when compared with White patients. Characterizing such disparities is the first step towards addressing treatment gaps in AF.

The use of prothrombin complex concentrate in chronic liver disease: A review of the literature.

Patients with chronic liver disease (CLD) and cirrhosis present a rebalanced hemostatic system in the three phases of haemostasis. This balance is however unstable and can easily tip towards bleeding or thrombosis. Management of both spontaneous bleeding and bleeding during invasive procedures remains a challenge in this patient population. Transfusion of blood products can result in circulatory overload and thereby worsen portal hypertension. As an alternative to fresh frozen plasma (FFP), prothrombin complex concentrates (PCC) may have merit in patients with liver disease because of their low volume. The impact of PCC in in-vitro spiking experiments of cirrhotic plasma is promising, but also warrants cautious use in light of thromboembolic risk. The majority of existing studies carried-out in CLD patients are retrospective or do not have an adequate control arm. A prospective study (the PROTON trial) was set up in 2013 to investigate the utility of PCC in patients undergoing liver transplantation. However, the study has never recruited the planned number of patients. Robust data on PCC safety in CLD is also required. The limited existing evidence does not seem to indicate an excessive thromboembolic risk. Currently, the utilisation of PCC in CLD cannot be routinely recommended but can provide an option for carefully selected cases in which other measures were not sufficient to control bleeding and after delicately weighing risks and benefits.

Investigation of Stroke Risk Factors and Prognostic Indicators in NVAF Patients with Low CHA2DS2-VASc Scores.

The prognosis of patients with nonvalvular atrial fibrillation (NVAF) with a low CHA2DS2-VASc score (0-1) following a stroke is not well studied. In this investigation, stroke risk factors and prognostic markers in low-risk NVAF patients who are nonetheless at risk for stroke were examined.From January 2012 to January 2022, we retrospectively assessed atrial fibrillation (AF) patients at Xiamen University's Zhongshan Hospital for ischemic stroke. Along with a control group of patients with CHA2DS2-VASc scores of 0-1 who weren't suffering from a stroke, patients with CHA2DS2-VASc scores of 0-1 at the time of stroke were included in the study. Using multivariate logistic regression, independent risk factors were identified. To assess the cumulative occurrences of in-hospital mortality in patients with NVAF-related stroke, the Kaplan-Meier method was used.The study included 156 out of 3.237 inpatients with AF-related stroke who had CHA2DS2-VASc ratings of 0-1. Left atrial diameter (LAD) (odds ratio [OR]: 1.858, 95% confidence interval (CI) 1.136-3.036, P = 0.013), D-dimer (OR: 2.569, 95% CI 1.274-5.179, P = 0.008), and NT-proBNP (OR: 4.558, 95% CI 2.060-10.087, P = 0.000) were found to be independent risk factors for stroke in NVAF patients with a low CHA2DS2-VASc score. During hospitalization, nine patients with NVAF-related stroke died. In patients with NVAF-related stroke, NT-proBNP (hazard ratio: 3.504, 95% CI 1.079-11.379, P = 0.037) was an indicator of mortality risk.Patients with NVAF and CHA2DS2-VASc scores of 0-1 had independent risk factors for stroke in the form of LAD, D-dimer, and NT-proBNP. Notably, in low-risk NVAF patients with stroke, NT-proBNP was discovered to be a potent predictor of in-hospital death.

Recommendations for risk minimization when using Janus kinase inhibitors for the treatment of chronic inflammatory skin diseases.

In accordance with article 20 of Regulation (EC) No 726/2004, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) has re-evaluated the safety of Janus kinase inhibitors for the treatment of inflammatory diseases and formulated safety information deviating from the previous indications in the respective summary of product characteristics of the products concerned. These refer to the consideration of a possibly increased risk of venous thromboembolic or severe cardiovascular events, an increased infection rate and an increase in the prevalence of skin cancer across drugs and indications. Therefore, in patients with independent risk factors (age 65 years and older, smokers or former smokers, patients with oral contraception or hormone replacement therapy and other risk factors), it is recommended to use Janus kinase inhibitors therapeutically only if there are no suitable treatment alternatives. To facilitate a pragmatic and thorough detection of high-risk patients in everyday clinical practice, an interdisciplinary checklist was developed that is suitable as a working tool from the perspective of the dermatologist.

Gender Differences in Atrial Fibrillation: From the Thromboembolic Risk to the Anticoagulant Treatment Response.

Atrial fibrillation (AF) is the most common cardiac arrhythmia associated with an increased thromboembolic risk. The impact of the female sex as an independent risk factor for thromboembolic events in AF is still debated. Background and Objectives: The aim of this review is to evaluate the gender-related differences in cardioembolic risk and response to anticoagulants among AF patients. Materials and Methods: The PubMed database is used to review the reports about gender differences and thromboembolic risk in atrial fibrillation. Results: Non-vitamin K oral anticoagulants (NOACs) represent the gold standard for thromboembolic risk prevention in patients with non-valvular atrial fibrillation (NVAF). Despite a similar rate of stroke and systemic embolism (SE) among men and women in NOACs or vitamin K antagonists (VKAs) treatment, the use of NOACs in AF women is associated with a lower risk of intracranial bleeding, major bleeding, and all-cause mortality than in men. Conclusions: The female sex can be defined as a stroke risk modifier rather than a stroke risk factor since it mainly increases the thromboembolic risk in the presence of other risk factors. Further studies about the efficacy and safety profile of NOACs according to sex are needed to support clinicians in performing the most appropriate and tailored anticoagulant therapy, either in male or female AF patients.

Elevated plasma Ninjurin-1 levels in atrial fibrillation is associated with atrial remodeling and thromboembolic risk.

BACKGROUND: Nerve injury-induced protein 1 (Ninj1) is elevated in various inflammatory diseases. The soluble form of Ninj1 yield by matrix metalloproteinase cleavage is a secreted protein and inhibits cell adhesion and inflammation. However, the role of plasma Ninj1 in atrial fibrillation (AF) has not been reported. The present study aimed to investigate the correlation between plasma Ninj1 levels and AF. METHODS: A total of 96 AF patients [age 66.00 (60.00, 72.00) years, male 56 (58.33%)] and 51 controls without AF [age 65.00 (55.00, 68.00) years, male 21 (41.18%)] were enrolled in this study. Plasma Ninj1 concentrations were detected using enzyme-linked immunosorbent assay. Also, the clinical characteristics, left atrial volume index (LAVI), CHA2DS2-VASc score, and HAS-BLED score were evaluated. RESULTS: Plasma Ninj1 levels were significantly higher in patients with AF than in controls (P < 0.001). Plasma Ninj1 levels were positively correlated with LAVI (P = 0.019) and CHA2DS2-VASc score (P = 0.024). Logistic regression analysis confirmed that the Ninj1 plasma levels were associated with AF (P = 0.009). The receiver operating characteristic analysis showed that plasma Ninj1 had a predictive value for AF (P < 0.001). CONCLUSIONS: Plasma Ninj1 levels were elevated in patients with AF, associated with left atrial enlargement and thromboembolic risk in AF.

Retroperitoneal hematoma in COVID-19 patients - case series.

COVID-19 patients, particularly those with severe pulmonary involvement, are at an increased thromboembolic risk related, among various causes, to the cytokine storm and excessive activation of the coagulation cascade and platelets. Different intensity of anticoagulation for them is proposed, mainly with low molecular weight heparins (LMWHs); in a confirmed pulmonary embolism (PE) the therapeutic dose of LMWH is routinely used. Some authors suggest that hemorrhagic complications in COVID-19 patients are rare. At the same time, one can find reports on internal bleeding, including retroperitoneal hematoma (RPH) and other abdominal hematomas. CASE REPORTS: The authors describe 5 cases (3 of those aged more than 80 years) with giant RPHs and with moderate/severe COVID-19 pneumonia, treated before RPH diagnosis with different enoxaparin doses. The therapeutic dose was given to the male with verified PE limited to the segmental/subsegmental pulmonary arteries and initially to the female in whom echocardiography was strongly suggestive of PE, yet this diagnosis was excluded on CT angiography. In one patient, the enoxaparin dose was escalated from 40 mg bd to 60 mg bd after the D-dimer increase. Two patients had bleeding complications despite the enoxaparin dose restricted to 40 mg/daily or bd. Two males had a coexistent psoas hematoma while in only one female there was a coexistent femoral hematoma. RPHs occurred between day 4 and 14 of hospitalization and all were treated conservatively. Three patients who died were particularly charged, so their deaths were not merely directly associated with RPH, which was closely analyzed in one autopsy performed. The authors underline that the choice of anticoagulation intensity in patients with COVID-19 pneumonia without venous thromboembolism seems sometimes difficult but recent publications indicate the low prophylactic enoxaparin dose as an optimal option. Anticoagulation dose escalation based only on the D-dimer level may not be appropriate for certain patients; moreover, the D-dimer increase is commonly observed during internal bleeding.

Acute femoral artery occlusion in a male with Duhring disease and COVID-19 pneumonia treated with baricitinib.

Arterial thromboembolic events (ATE) in COVID-19, similarly as venous thromboembolism (VTE), are observed mainly in severely ill patients. ATE include brain, heart, aortic, and peripheral ischemic complications which usually aggravate a course of the disease leading to lifethreatening conditions. A CASE REPORT: The authors describe a case of a 53-year-old male with Duhring disease in the remission period admitted due to severe COVID-19 pneumonia. The patient was treated with ceftriaxone (2000 mg once daily), dexamethasone (8 mg once daily), enoxaparin (60 mg twice daily), baricitinib (4 mg once daily), and remdesivir (200 mg on the first day, followed by 100 mg within 4 consecutive days); he required high flow oxygen therapy. On day 5 of hospitalization, he began to suffer from pain of the right lower extremity; in physical examination the limb was cold with absent femoral, popliteal, and pedal pulses. Urgent computed tomography angiography revealed total occlusion of the right superficial femoral artery (SFA) in the absence of any atherosclerotic plaques in the aorta. The patient was intubated and transferred to department of vascular surgery, where a giant clot was removed from SFA. Unfortunately, the patient outcome was unfavorable due to respiratory failure progression. The authors underline that ATE may occur even in anticoagulated patients and that association of some therapeutic options of COVID-19, like janus kinase (JAK) inhibitors use with an increased risk of ATE, should not be excluded.

[Tranexamic acid for bleeding prophylaxis in orthopedic surgery and trauma-standard or customized therapy?] / Tranexamsäure zur Blutungsprophylaxe bei Trauma und orthopädischen Eingriffen ­ Standard oder individualisierte Anwendung?

The use of tranexamic acid (TXA) is established in the treatment of bleeding, especially of bleeding due to hyperfibrinolysis. In recent years the prophylactic use of TXA in trauma and orthopedic surgery has increased leading to open questions regarding potentially associated risks and a possible classification as off label use. The available literature provides a sound basis for the recommendation that TXA can be used in these indications provided that an individual risk assessment is done in patients with increased risks for thromboembolic complications. Although the prophylactic use of TXA in orthopedic surgery and trauma is not explicitly listed in the product characteristics, it should not be regarded as an off label use.

Obesity and hormonal contraception: an overview and a clinician's practical guide.

BACKGROUND: The growing prevalence of obesity among the fertile female population poses a considerable problem to contraceptive providers. Obese women, who are more at risk for venous thromboembolism and cardiovascular events due to their condition, might be at an even higher risk of developing thromboembolic events when on medical contraception. Combined hormonal contraceptives might be less effective in obese women and may lead to unacceptable metabolic side effects for this population. In addition, the lack of safety data for weight loss drugs and the higher risk for complications during and after pregnancy require a close surveillance of the fertility status of obese patients. OBJECTIVE: The aim of this narrative review is to summarize the available medical contraceptive options and to give the readers a practical guidance for a wise contraceptive choice with regards to obesity. METHODS: A general literature review of peer-reviewed publications on the topic "obesity and contraception" was performed using the PubMed database. RESULTS: Nowadays, there are many useful tools that help clinicians in choosing among the wide range of therapeutic possibilities, such as the World Health Organization (WHO) Medical Eligibility Criteria for contraceptive use. Furthermore, the great diversity of hormonal contraceptive formulations (combined hormonal formulations; progestin-only methods) and active substances (different estrogens and progestins) allow physicians to tailor therapies to patients' clinical peculiarities. CONCLUSION: Long-acting reversible contraceptives [progestin-only implants, levonorgestrel-intra-uterine devices (IUDs) and copper IUDs] and progestin-only methods in general are excellent options for many categories of patients, including obese ones. LEVEL OF EVIDENCE: V, narrative review.

Combined use of antifibrinolytics and activated prothrombin complex concentrate (aPCC) is not related to thromboembolic events in patients with acquired haemophilia A: data from FAIR Registry.

Antifibrinolytics combined with aPCC are not routinely administered to patients with acquired hemophilia A due to increased thrombotic risk. This association normalizes clot stability, and improves the efficacy of therapy, but can increase the risk of severe side effects. Due to these premises it has always raised doubts and perplexities in the clinics. We now report the data of the "FEIBA® on acquired haemophilia A Italian Registry (FAIR Registry)", a retrospective-prospective study that included 56 patients. This is the first study that assessed the clinical response of the combination of aPCC and antifibrinolytic agents in patients with acquired haemophilia A. A total of 101 acute bleeds were treated with aPCC. Antifibrinolytic agents were used in the treatment of 39.6% of total bleeds, based on both, a clinical assessment and an evaluation of bleeding. Twenty-five of the 30 patients (57.1%) treated with antifibrinolytic drugs showed serious co-morbidity. Among them, 40% presented severe cardiovascular diseases. All bleeds treated with combined therapy had a shorter duration of treatment (mean reduction 16.3%). All the treated patients presented a good tolerability and no arterial or venous thromboembolic events were reported. In our retrospective registry the combination of antifibrinolytics and aPCC appears safe and effective in the treatment of patients with AHA, especially in the case of severe and life-threatening bleeding, but this hypothesis needs to be confirmed in adequate, larger clinical trials.

Atrial flutter and embolic risk: The relationship between atrial flutter cycle length and left atrial appendage function.

BACKGROUND: The potential for thromboembolism in atrial flutter (AFL) is different from atrial fibrillation. AFL cycle length (AFL-CL) may be related to reduced left atrial appendage (LAA) function. Very rapid AFL-CL can lead to mechanical and electrophysiological disorders that contribute to lower LAA emptying velocity (LAEV). The aim of this study is to relate atrial flutter cycle length with LAEV and its role in thrombogenesis. METHODS: Cross-sectional study of patients with atrial flutter AFL who underwent transoesophageal echocardiography (TEE) before catheter ablation or electric cardioversion. AFL-CL in milliseconds was measured with a 12-lead EKG or in intracardiac records. RESULTS: We included 123 patients. There was correlation between AFL-CL and LAEV (r = 0.34; p = 0.003) in typical AFL. Cycle length, LA size and atypical flutter were predictors of low LAEV on multivariate analysis. An index multiplying atrial rate (bpm) during the arrhythmia versus left atrial size(mm) >11,728 was associated with spontaneous echogenic contrast and/or left atrial thrombus on TEE (C-statistic = 0.71; CI95%0.60-0.81). CONCLUSIONS: There was a significant relationship between the AFL-CL and LAEV. The LAEV was affected by the LA size, the type of atrial flutter and the AFL-CL. A new index, relating the atrial rate with the left atrial size, was able to identify a higher occurrence of spontaneous echogenic contrast and/or left atrial thrombus.

Clinical Impact of Oral Anticoagulation in Patients with Atrial High-rate Episodes.

BACKGROUND: Atrial high-rate episodes (AHREs) are common in pacemaker patients. Our aims were to compare patients with AHREs to those without them and to assess if, in those with AHREs, the initiation of oral anticoagulation (OAC) has any clinical impact on the occurrence of ischemic and hemorrhagic events. METHODS: From 2014-2017 we selected patients with pacemaker in whom AHREs were detected. AHREs were defined as episodes lasting more than 6 minutes if the electrogram was available or more than 6 hours if not. We used an age- and gender-matched population with pacemaker but no AHRE as a control group (observational study). Those with AHRE were referred to their assistant physician to decide OAC initiation, based on individual circumstances (interventional study). In interventional study, the primary outcome was a composite of systemic thromboembolism or major bleeding. Secondary outcomes were clinical relevant nonmajor bleeding, major and nonmajor bleeding, CV death, and death from all causes. RESULTS: AHREs were detected in 86 patients: 69 patients initiated OAC and the remaining 17 patients did not. When comparing patients with and without AHRE, baseline characteristics were not different between the groups, except for indexed left atrium volume-40 mL (IQR: 34-50) in AHRE group versus 35 mL (IQR: 34-40) in control group (P = .014). AHREs were associated with future development of atrial fibrillation (AF) and the risk was higher if AHRE duration was superior to 6 hours. Death and cardiovascular (CV) death were not significantly different between the groups with and without AHRE. Primary outcome occurred in 4.9 per 100 person-year in OAC group versus 3.4 per 100 person-year in non-OAC group (HR 1.4, 95% CI .2-11.3, P = .78). Secondary outcomes were not significantly different in the groups. CONCLUSIONS: In this group of patients with pacemakers, the presence of AHREs was useful for predicting the future development of AF and the risk of AF was higher in those with a longer duration of AHRE. In the AHRE group, OAC therapy was not associated with a significant difference in the risk of thromboembolism or major bleeding.

Fewer thromboembolic events after implementation of a venous thromboembolism risk stratification tool.

BACKGROUND: Deep venous thrombosis and pulmonary embolus are leading preventable causes of death after surgery. Venous thromboembolism (VTE) prophylaxis management guidelines, with evidenced-based recommendations, are available in the literature. However, over 40% of "at-risk" surgical patients fail to receive appropriate VTE prophylaxis. Decision support-based interventions to reduce venous thromboembolic events were explored. METHODS: A venous thromboembolic risk stratification tool embedded in the electronic medical record, Epic, linking risk category to venous thromboembolic prophylaxis order sets was created, implemented, and analyzed for general surgery patients. Logistic regression analysis was used to compare rates of venous thromboembolic events before and after the intervention, controlling for age, gender, race, body mass index, inpatient status, transfer status, elective/emergent case status, American Society of Anesthesiologists classification, and wound classification. RESULTS: Venous thromboembolic events in the preintervention and postintervention periods were 55 (1.25%) and 12 (0.64%), respectively (P = 0.033). All-cause mortality events decreased after intervention from 49 (1.12%) to 14 (0.75%; P = 0.187). Multivariable analyses show that the risk of a venous thromboembolic event after intervention was half (odds ratio = 0.532; 95% confidence interval, 0.284-0.997; P = 0.049) as likely compared to that in the preintervention period. From 2012 to 2015, our institution moved from the ninth decile (poor) to the first decile (best) for the incidence of venous thromboembolic events among 760 National Surgical Quality Improvement Program hospitals across the nation. CONCLUSIONS: Postoperative thromboembolic events decreased after implementation of a VTE risk stratification tool, linking risk category to venous thromboembolic prophylaxis order sets, embedded in the electronic medical record, Epic.

DAPT plus anticoagulant therapy: The difficult coexistence post-ACS in older patients with atrial fibrillation.

Atrial fibrillation (AF) and coronary artery disease requiring percutaneous coronary intervention (PCI) and stenting often coexist in older patients. This poses the difficult problem of concurrent anticoagulant and double antiplatelet therapy (triple therapy). Current treatment guidelines do recommend triple therapy, especially in the course of acute coronary syndrome (ACS), with limitations due to an excessive risk of bleeding associated with this therapeutic regimen. This review summarizes randomized clinical trials and observational studies that compared triple therapy with a variety of different therapeutic options. Although the available evidence is not completely satisfactory and other studies are urgently needed, alternative regimens to triple therapy in AF patients undergoing PCI and stenting are promising, at least in terms of safety.

Atrial high-rate episodes and stroke prevention.

While the benefit of oral anticoagulants (OACs) for stroke prevention in patients with atrial fibrillation (AF) is well established, it is not known whether oral anticoagulation is indicated in patients with atrial high-rate episodes (AHRE) recorded on a cardiac implantable electronic device, sometimes also called subclinical AF, and lasting for at least 6 min in the absence of clinically diagnosed AF. Clinical evidence has shown that short episodes of rapid atrial tachycarrhythmias are often detected in patients presenting with stroke and transient ischaemic attack. Patients with AHRE have a higher likelihood of suffering from subsequent strokes, but their stroke rate seems lower than in patients with diagnosed AF, and not all AHRE episodes correspond to AF. The prognostic and pathological significance of AHRE is not yet fully understood. Clinical trials of OAC therapy are being conducted to determine whether therapeutic intervention would be beneficial to patients experiencing AHRE in terms of reducing the risk of stroke.