[Assessing the Impact of in-Hospital Formulary Policies on the Prescription Patterns of Direct Oral Anticoagulants (DOACs)].

Prescribing direct oral anticoagulants (DOACs) with off-label dosage and administration is discouraged due to concerns about their effectiveness and safety. Consequently, our hospital pharmacist established a formulary with physicians for oral anticoagulants. Our study aimed to assess the adherence to this formulary by investigating the rate of appropriate DOAC prescribing. We included patients who were newly prescribed or continued on DOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) at our hospital. We calculated the percentage of patients prescribed the correct dosage and administration according to the package insert and compared this across three time periods: pre-intervention (period A; April-September 2019), post-intervention phase 1 (period B; August 2021-January 2022), and post-intervention phase 2 (period C; November 2022-April 2023). We also examined the number of inquiries and consultation requests made by hospital pharmacists regarding DOAC dosage and administration. A total of 782 patients were surveyed (191 in period A, 263 in period B, and 328 in period C). The appropriate prescribing rates for DOACs were 79.1% in period A, 84.4% in period B, and 86.6% in period C. The proportion of cases where hospital pharmacists questioned or consulted doctors about DOAC dosage and administration was 3.7% in period A, 6.1% in period B, and 10.1% in period C. These findings indicate that active intervention by hospital pharmacists using the formulary regarding oral anticoagulant formularies may promote appropriate DOAC use.

Direct Oral Anticoagulants for Rheumatic Heart Disease-Associated Atrial Fibrillation Post-Bioprosthetic Mitral Valve Replacement.

BACKGROUND: The efficacy of direct oral anticoagulants (DOACs) in preventing ischemic and thromboembolic events may be suboptimal in atrial fibrillation (AF) patients with rheumatic mitral stenosis. However, their safety and effectiveness after mitral valve replacement (MVR) using bioprosthetic valves is unclear. OBJECTIVES: This study sought to evaluate the safety and effectiveness of DOACs vs warfarin among patients with rheumatic heart disease (RHD)-associated AF after bioprosthetic MVR. METHODS: We performed an observational analysis identifying patients with RHD and AF who underwent bioprosthetic MVR. Primary effectiveness and safety outcomes were ischemic events and major bleeding, respectively. Secondary outcomes included all-cause mortality, cardiac thrombosis, myocardial infarction, and all-cause hospitalization. Propensity score matching was performed to account for the differences in baseline characteristics and comorbidities. RESULTS: A total of 3,950 patients were identified; 76% were on warfarin and 24% on DOAC post-MVR. The DOAC group had a higher burden of baseline comorbidities and prior cardiovascular procedures compared with the warfarin group. The propensity score matching balanced baseline characteristics in 1,832 patients (916 in each group), with a mean age of 69 years. At the 5-year follow-up, DOACs were associated with a lower incidence of major bleeding compared with warfarin (HR: 0.76; 95% CI: 0.62-0.94), with no significant difference in ischemic events, mortality, cardiac thrombosis, myocardial infarction, or hospitalization. CONCLUSIONS: Among patients with RHD-associated AF patients post-bioprosthetic MVR, DOACs are associated with lower major bleeding and comparable effectiveness, indicating a potential alternative to warfarin. Further randomized controlled trials are warranted to validate these findings in this population.

Bibliometric and visualized analysis on hip fracture surgery and venous thromboembolism.

Background: Hip fractures primarily occur in older people and represent a significant public health issue due to their high incidence and mortality rate. The concurrent occurrence of venous thromboembolism (VTE) during the perioperative period exacerbates the threat to patient health. Methods: We retrieved all articles related to hip fracture surgery and venous VTE from the Web of Science core collection database from 2000 to 2023. For bibliometric analysis, we extracted relevant information, including year of publication, country, institution, journal, impact factor, title, author, category, reference, keywords, number of citations, average number of citations, and H-index. Results: A total of 1079 articles were retrieved, with 67 countries, 341 institutions, and 256 journals participating in research on hip fracture surgery and venous thromboembolism. The overall research showed an increasing trend. The United States, Harvard University, Injury-International Journal of The Care of The Injured, and Lassen MR are the leading country, institution, journal, and author respectively, in terms of publication. Research directions in this field mainly include the impact of preoperative anticoagulation on fracture surgery, intraoperative blood protection strategies, and postoperative prevention and treatment of VTE. Hotspots and trends in research include the relationship between direct oral anticoagulants and surgical timing, perioperative blood protection, intertrochanteric fractures, and geriatric traumatic fractures. Conclusions: This study constructed the knowledge structure of hip fracture surgery and VTE and identified research hotspots and trends. Future research should focus on developing a prediction system for VTE in hip fracture surgery to guide individualized prevention and treatment.

Dual direct oral anticoagulant therapy in challenging thrombosis: a case series.

Background: While anticoagulation therapy is highly effective at treating venous thromboembolism, some patients can develop rapidly progressive thrombosis in multiple organs or sites despite therapeutic anticoagulation. Effective strategies to manage life-threatening thrombosis in these patients are elusive. Objectives: We describe our experience using dual direct oral anticoagulant (DOAC) therapy with a factor (F)Xa inhibitor (such as rivaroxaban or apixaban) and a FIIa inhibitor (dabigatran) for refractory cases of thrombosis. Methods: A retrospective chart review of all patients treated with simultaneous dabigatran and an oral FXa inhibitor at our institution was conducted. We included all patients over the age of 18. The study was approved by the University of British Columbia Research Ethics Board (REB number: H23-02575). Results: Eight patients were included. All patients initiated standard therapeutic anticoagulation upon diagnosis of acute venous thromboembolism with a median of 3 breakthrough thrombotic events prior to dual DOAC use. Five patients had a positive heparin-induced thrombocytopenia screen, but only 2 had heparin-induced thrombocytopenia confirmed on serotonin release assay testing. There were no recurrent deep vein thrombosis, pulmonary embolism, or bleeding events during dual DOAC use. Most patients ultimately transitioned to a single oral FXa inhibitor. Conclusion: Dual DOAC therapy may be a useful strategy for managing challenging thrombosis cases resistant to conventional anticoagulation. Further research is warranted to validate these findings and explore the broader applicability of dual DOAC therapy in challenging thrombotic scenarios.

Oral anticoagulation in patients with hypertrophic cardiomyopathy and non-valvular atrial fibrillation in Japan.

AIMS: There are limited data to support direct oral anticoagulant (DOAC) use in patients with hypertrophic cardiomyopathy (HCM) and non-valvular atrial fibrillation (NVAF). The current study investigated the safety and effectiveness of DOACs versus warfarin in patients in Japan. METHODS: This retrospective observational study assessed a Japanese cohort of patients diagnosed with HCM and NVAF between July 2011 and June 2021 using a Japanese claims database. Propensity score (PS) matching (2:1 DOAC:warfarin) using the nearest-neighbour method was applied to balance demographic and clinical characteristics between treatment groups. The primary outcomes were the risk of major bleeding and any bleeding (major or minor). Secondary outcomes included describing baseline demographic and clinical characteristics and the risk of stroke/systemic embolism (SE). RESULTS: After PS matching, 2955 DOAC- and 1603 warfarin-treated patients were assessed. The mean [standard deviation (SD)] age in the DOAC and warfarin groups was 74.8 (10.5) and 75.3 (10.2) years, respectively. The majority of patients were male (DOAC, 58.8%; warfarin, 59.6%), had comorbidities (DOAC, 97.5%; warfarin, 96.6%), and were treated with ß-blockers (DOAC, 62.5%; warfarin, 62.3%). The risk of major and any bleeding was similar across cohorts [hazard ratio (HR), 0.80; 95% confidence interval (CI), 0.50-1.27; P = 0.336 and HR, 0.93; 95% CI, 0.78-1.11; P = 0.420] while the risk of stroke/SE was lower among patients treated with DOACs (HR, 0.67; 95% CI, 0.47-0.96; P = 0.027). Factors associated with an increased risk of major bleeding included prior bleeding (HR, 1.97; 95% CI, 1.22-3.17) and chronic kidney disease (HR, 1.87; 95% CI, 1.10-3.18). An increased risk of stroke/SE was associated with prior ischaemic stroke (HR, 2.97; 95% CI, 2.05-4.29), peripheral arterial disease (HR, 1.88; 95% CI, 1.22-2.88) and chronic kidney disease (HR, 1.87; 95% CI, 1.24-2.83). CONCLUSIONS: DOAC-treated patients had a lower risk of stroke/SE and a comparable risk of bleeding compared with warfarin-treated patients. Prior stroke was shown to augment stroke risk by approximately three-fold. This large real-world study suggests that patients diagnosed with HCM and NVAF can be safely and effectively treated with DOACs in Japan.

[Implementation of edoxaban anti-Xa activity assay in a hospital laboratory and evaluation of its analytical performance]. / Mise en place du dosage de l'activité anti-Xa de l'edoxaban dans un laboratoire hospitalier et évaluation de ses performances analytiques.

Edoxaban is a direct oral anticoagulant available in Europe but not in France. Given the high tourist traffic in France, understanding the pharmacology of edoxaban and the availability of its laboratory testing seemed crucial in emergency situations. The aim of this work was to describe the methodology for measuring the anti-Xa activity of edoxaban, highlighting pre-analytical and analytical aspects, along with essential clinico-biological data for therapeutic guidance. The analysis was performed using the chromogenic method on the STAR-Max analyzer, with the STA®-Liquid ANTI-Xa kit (Diagnostica Stago®). Anti-Xa Edoxaban level measurement has a detection limit of 15 ng/mL, a quantification limit of 20 ng/mL and a linearity limit of 400 ng/mL. Repeatability, intermediate precision, accuracy, and measurement uncertainty studies were conducted to assess method performance, meeting quality requirements. The comparison between two STAR-Max® analyzers showed excellent results with linear regression and a low bias with good precision and no loss of dispersion regardless of edoxaban levels. In conclusion, although the measurement of edoxaban level may be rarely necessary in clinical practice, its implementation is straightforward. The availability of edoxaban in neighboring countries, underscores the importance of having its measurement available in hospital laboratories.

Comparison of direct oral anticoagulant (DOAC) versus low-molecular-weight heparin (LMWH) for venous thromboprophylaxis after radical cystectomy: A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: Radical cystectomy in bladder cancer patients can result in postoperative complications, including venous thromboembolism (VTE), with an incidence reported between 3% and 11.6%. Although low-molecular-weight heparin (LMWH) is the recommended prophylactic treatment, challenges such as financial constraints and patient adherence remain. Direct Oral Anticoagulants (DOACs) present an alternative, but their comparative efficacy and safety against LMWHs in preventing VTE after radical cystectomy need further evaluation. This study aims to compare the efficacy and safety of LMWHs vs. DOACs for VTE prophylaxis following radical cystectomy. MATERIALS AND METHODS: A systematic search was performed across 3 electronic databases to identify relevant studies utilizing DOACs and LMWHs for VTE prophylaxis after radical cystectomy. The primary outcomes of interest were VTE and bleeding events. Fixed-effect models were employed to summarize the outcomes, with results presented as odds ratios (OR) and their corresponding 95% confidence intervals (CI). RESULTS: The analysis included a total of 541 patients from three studies. The pooled data indicated that patients on DOACs had a statistically nonsignificant lower odds of VTE (OR 0.41 [95% CI 0.13-1.36], P = 0.15) and a statistically nonsignificant higher odds of bleeding events (OR 3.03 [95% CI 0.53-17.23], P = 0.21). CONCLUSIONS: Our findings suggest that DOACs are comparable to LMWHs in terms of VTE and bleeding events for thromboprophylaxis following radical cystectomy. The choice of prophylactic agent can be guided by patient preference and clinical judgment. However, additional randomized controlled trials with larger sample sizes are necessary to confirm these findings.

Risks of oral anticoagulants: Analysis of adverse drug reactions reported to the Portuguese National Pharmacovigilance System.

Cardiovascular diseases are the leading cause of death globally, making the use of oral anticoagulants for prevention increasingly important. Historically, warfarin has played a significant role in this context. In recent years, introduction of new oral anticoagulants, such as rivaroxaban, apixaban, dabigatran, and edoxaban, has been seen. This study evaluates the risk associated with the use of oral anticoagulants by analyzing spontaneous adverse drug reactions reported to the Portuguese Pharmacovigilance System from 2012 to 2021. The study includes 951 adverse drug reactions reports, with the majority (n = 770; 80.97%) classified as serious. Of the 770 serious adverse drug reactions reports, the most commonly reported seriousness criterion was "Clinically Important" (n = 350; 45.45%). In terms of demographics, there was a higher reporting rate among the elderly population, with a greater prevalence of females. The System Organ Class group with the highest number of adverse drug reactions was "Gastrointestinal disorders," with the most commonly reported Preferred Term being "Gastrointestinal hemorrhage," and dabigatran was the most frequently reported drug. In summary, oral anticoagulants have adverse drug reactions that require continuous monitoring. Accurate identification and monitorization of adverse drug reactions is an important starting point to improve drug safety in population.

Prognosis of Patients With Ischemic Stroke With Prior Anticoagulant Therapy: Direct Oral Anticoagulants Versus Warfarin.

BACKGROUND: Direct oral anticoagulants (DOACs) have been the drug of choice for preventing ischemic stroke in patients with atrial fibrillation since 2014. In previous studies, the stroke risk while taking warfarin was 2 per 100 patient-years and 1.5% per year while taking DOACs. We hypothesized that even if ischemic stroke occurred during anticoagulation therapy with DOACs, the prognosis was likely to be better than that with warfarin. METHODS AND RESULTS: Data from 2002 to 2019, sourced from a nationwide claims database, were used to identify atrial fibrillation patients using International Classification of Diseases codes. Patients who experienced an ischemic stroke during anticoagulation were categorized by the drugs used (warfarin, dabigatran, apixaban, rivaroxaban, and edoxaban). The primary outcome was mortality within 3 months and 1 year after the ischemic stroke. Among the 9578 patients with ischemic stroke during anticoagulation, 3343 received warfarin, and 6235 received DOACs (965 dabigatran, 2320 apixaban, 1702 rivaroxaban, 1248 edoxaban). The DOACs group demonstrated lower risks of 3-month (adjusted hazard ratio [HR], 0.550, [95% CI, 0.473-0.639]; P<0.0001) and 1-year mortality (adjusted HR, 0.596 [95% CI, 0.536-0.663]; P<0.0001) than the warfarin group. Apixaban and edoxaban within the DOAC group exhibited particularly reduced 1-year mortality risk compared with other DOACs (P<0.0001). CONCLUSIONS: Our study confirmed that DOACs have a better prognosis than warfarin after ischemic stroke. The apixaban and edoxaban groups had a lower risk of death after ischemic stroke than the other DOAC groups.

Successful direct oral anticoagulant management of asymptomatic superior mesenteric vein thrombosis after adjuvant chemotherapy for colorectal cancer patient: A case report.

Owing to advances in cancer treatment and the diversification of treatment methods, cancer-associated thrombosis is increasing. Cancer can cause blood clots by activating the blood clotting system, increasing clotting factors through inflammation, reducing blood flow due to immobilization and damaging blood vessels through treatments such as chemotherapy. In clinical practice, superior mesenteric vein (SMV) thrombosis is occasionally observed in patients with cancer; however, certain cases of asymptomatic thrombosis can be serious. In the present case, a 71-year-old woman underwent laparoscopic high anterior resection for colorectal cancer. The patient received capecitabine as postoperative adjuvant chemotherapy for 6 months. Contrast-enhanced CT after the completion of chemotherapy revealed a sizable thrombus in the SMV. The thrombus occupied the SMV lumen without evident intestinal ischemia. D-dimer levels were elevated. Since the patient remained asymptomatic, edoxaban (30 mg/day) was administered in an outpatient setting. Six months later, contrast-enhanced CT confirmed thrombus resolution. No hemorrhagic events were observed during edoxaban treatment. In conclusion, cancer and chemotherapy are risk factors for thrombosis, indicating that regular D-dimer measurements may be necessary during cancer treatment. In addition, edoxaban may be an effective therapeutic tool for SMV thrombosis during chemotherapy for cancer.

A Case of Rivaroxaban-induced Hematomyelia of Thoracic Spinal Cord in Patient with Acute Renal Failure.

Hematomyelia associated with direct oral anticoagulants (DOACs) is rare. In this report, a case of a 78-year-old male with paraplegia due to hematomyelia after medication of rivaroxaban, which is the first case in which acute renal failure is closely associated with the onset and underwent surgical evacuation is presented. The patient was initially misdiagnosed as a spinal cord infarction, and appropriate therapeutic intervention was not provided. One year later, the patient's symptoms did not improve, he is dependent on a wheelchair for daily activities, and cystostomy was performed. During administration of DOACs, hemorrhagic lesion should be strongly suspected in a patient with acute renal failure.

Novel Anticoagulants for Stroke Prevention in Atrial Fibrillation: A Comprehensive Review.

Atrial fibrillation (AF) is a prevalent cardiac arrhythmia associated with an increased risk of stroke due to disrupted heart function and potential clot formation. This review examines current management strategies for stroke prevention in AF, focusing on the efficacy, safety, and long-term outcomes of anticoagulation therapies. Anticoagulants, including novel oral anticoagulants (NOACs) and vitamin K antagonists, play a crucial role in reducing stroke risk by preventing clot formation in the heart. Recent studies highlight NOACs as superior alternatives to traditional therapies, offering improved safety profiles and enhanced patient adherence. Despite the risk of bleeding complications, judicious use of anticoagulants significantly improves clinical outcomes in AF patients. The review synthesizes evidence from clinical trials and meta-analyses to underscore the pivotal role of NOACs in transforming stroke prevention strategies in AF. Moreover, it discusses emerging interventions such as left atrial appendage occlusion and emphasizes the importance of personalized, patient-centered care in optimizing treatment decisions for AF patients at risk of stroke.

Can edoxaban be used at extremes of bodyweight and in patients with a creatinine clearance ≥95 ml/min? - A population pharmacokinetic analysis.

BACKGROUND: Clinical evidence surrounding edoxaban use in patients weighing <50 kg and >120 kg is lacking. The International Society of Thrombosis and Haemostasis Scientific and Standardisation Committee suggests avoiding edoxaban in patients >120 kg. Additionally, concerns exist regarding decreased efficacy in patients prescribed edoxaban for atrial fibrillation with a creatinine clearance (CrCl) >95 ml/min, a finding of the ENGAGE AF-TIMI 48 trial when edoxaban was compared to warfarin. OBJECTIVE: To derive a population pharmacokinetic (PopPK) model using clinical practice data, to understand the impact of bodyweight and renal function on edoxaban pharmacokinetics. METHOD: Edoxaban plasma concentrations and patient characteristics were collated from King's College Hospital anticoagulation clinics between 11/2016 and 08/2022. A PopPK model was developed using non-linear mixed effects modelling and used to simulate edoxaban concentrations at the extremes of bodyweight and with varying renal function. RESULTS: Data from 409 patients (46 < 50 kg, 34 > 120 kg and 123 with a CrCl > 95 ml/min) provided 455 edoxaban plasma concentrations. A one-compartment model with between-subject variability on clearance with a proportional error model best described the data. The most significant covariates impacting on edoxaban exposure were CrCl and bodyweight. Our work suggests that edoxaban exposure in patients weighing up to 140 kg is comparable to those weighing 75 kg. Edoxaban exposure is reduced in patients weighing <50 kg due to the recommended dose reductions. There is also a reduction in AUCss when CrCl > 95 ml/min compared to CrCl 80 ml/min. CONCLUSIONS: Our population PK model for edoxaban suggests that renal function is a key driver for overall edoxaban exposure. Further clinical outcome data is required to understand clinical effectiveness and adverse outcomes.

IV Thrombolysis for Acute Ischemic Stroke with Unknown Onset in Patients on Oral Anticoagulation.

INTRODUCTION: IV thrombolysis (IVT) is established in the unknown or extended time window based on multimodal imaging. Further, increasing evidence exists regarding IVT in patients on oral anticoagulation including direct oral anticoagulants (DOACs). However, data on IVT in ischemic stroke patients on oral anticoagulation with unknown time of stroke onset are sparse. METHODS: This study bases on the longitudinal cohort study Stroke Research Consortium in Northern Bavaria (STAMINA; ClinicalTrials.gov Identifier: NCT04357899). Acute ischemic stroke patients treated with IVT in the unknown or extended time window from January 2015 to December 2019 were included. Patient selection was based on multimodal CT or MRI. Patients on oral anticoagulation (vitamin-K antagonist [VKA] or DOAC within 48 h) were eligible for IVT based on INR measurement (VKA) or plasma levels (DOAC) according to an institutional protocol. Primary outcomes were the incidence of any and symptomatic intracranial hemorrhage. RESULTS: Of 170 ischemic stroke patients treated with IVT in the unknown or extended time window, 151 had no oral anticoagulation at stroke onset and 19 were on oral anticoagulation (6 on VKA and 13 on DOAC). The risk of symptomatic ICH according to ECASS II criteria was similar between the patients with and without oral anticoagulation (1 [5.3%] vs. 4 [2.7%], p = 0.453). After adjustment for confounding factors, pre-medication with oral anticoagulation was not associated with symptomatic ICH (aOR 1.02 [0.09-11.02], p = 0.988). CONCLUSION: IVT for ischemic stroke with unknown onset appeared safe in selected patients on oral anticoagulation with both DOAC and VKA.

Development and Validation of a Predictive Model for Intracranial Haemorrhage in Patients on Direct Oral Anticoagulants.

BACKGROUND: Intracranial haemorrhage (ICH) poses a significant threat to patients on Direct Oral Anticoagulants (DOACs), with existing risk scores inadequately predicting ICH risk in these patients. We aim to develop and validate a predictive model for ICH risk in DOAC-treated patients. METHODS: 24,794 patients treated with a DOAC were identified in a province-wide electronic medical and health data platform in Tianjin, China. The cohort was randomly split into a 4:1 ratio for model development and validation. We utilized forward stepwise selection, Least Absolute Shrinkage and Selection Operator (LASSO), and eXtreme Gradient Boosting (XGBoost) to select predictors. Model performance was compared using the area under the curve (AUC) and net reclassification index (NRI). The optimal model was stratified and compared with the DOAC model. RESULTS: The median age is 68.0 years, and 50.4% of participants are male. The XGBoost model, incorporating six independent factors (history of hemorrhagic stroke, peripheral artery disease, venous thromboembolism, hypertension, age, low-density lipoprotein cholesterol levels), demonstrated superior performance in the development dateset. It showed moderate discrimination (AUC: 0.68, 95% CI: 0.64-0.73), outperforming existing DOAC scores (ΔAUC = 0.063, P = 0.003; NRI = 0.374, P < 0.001). Risk categories significantly stratified ICH risk (low risk: 0.26%, moderate risk: 0.74%, high risk: 5.51%). Finally, the model demonstrated consistent predictive performance in the internal validation. CONCLUSION: In a real-world Chinese population using DOAC therapy, this study presents a reliable predictive model for ICH risk. The XGBoost model, integrating six key risk factors, offers a valuable tool for individualized risk assessment in the context of oral anticoagulation therapy.

Group-based trajectory modeling to identify adherence patterns for direct oral anticoagulants in Medicare beneficiaries with atrial fibrillation: a real-world study on medication adherence.

BACKGROUND: Suboptimal adherence to direct oral anticoagulants (DOACs) among atrial fibrillation (AF) patients remains currently a major concern due to the increased risk of cardiac and thromboembolic events. AIM: To identify longitudinal distinct trajectories of DOAC adherence and sociodemographic and clinical factors associated with each trajectory. METHOD: Patients with AF who were prescribed with DOAC from July 2016-December 2017 were identified among patients enrolled in the Medicare Advantage Plan. Patients were followed up for a year after the index date to calculate the monthly proportion of days covered (PDC). The monthly PDC was incorporated into the logistic group-based trajectory model to evaluate distinct patterns of adherence. A multinomial regression model was carried out to assess various predictors associated with each trajectory. Sub-group analysis was conducted among incident DOAC users. RESULTS: Total of 1969 patients with AF, four distinct trajectories of adherence were selected: adherent 36.8%, gaps in adherence 9.3%, gradual decline in adherence 29.7%, and rapid decline in adherence 24.2%. Significant predictors associated with suboptimal adherence trajectories were age (75 years or older), gender (male vs female), low-income subsidy health plan, prevalent users, and presence of comorbidities. Among 933 incident users, three adherence trajectories were identified: adherent trajectory (31.8%), rapid decline in adherence (32.5%), and gradual decline in adherence (35.6%). The significant predictors among incident users were gender (male vs female), low-income subsidy health plan, HAS-BLED score ≥ 2, and presence of coronary artery disease. CONCLUSION: Adherence to DOACs was suboptimal among the total population and incident users.

Direct oral anticoagulants in embolic stroke of undetermined source: an updated meta-analysis.

The efficacy and safety of direct oral anticoagulants (DOAC) in patients with embolic stroke of undetermined source (ESUS) remains unclear. We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCT) comparing DOACs versus aspirin in patients with ESUS. Risk ratios (RR) and 95% confidence intervals (CI) were computed for binary endpoints. Four RCTs comprising 13,970 patients were included. Compared with aspirin, DOACs showed no significant reduction of recurrent stroke (RR 0.95; 95% CI 0.84-1.09; p = 0.50; I2 = 0%), ischemic stroke or systemic embolism (RR 0.97; 95% CI 0.80-1.17; p = 0.72; I2 = 0%), ischemic stroke (RR 0.92; 95% CI 0.79-1.06; p = 0.23; I2 = 0%), and all-cause mortality (RR 1.11; 95% CI 0.87-1.42; p = 0.39; I2 = 0%). DOACs increased the risk of clinically relevant non-major bleeding (CRNB) (RR 1.52; 95% CI 1.20-1.93; p < 0.01; I2 = 7%) compared with aspirin, while no significant difference was observed in major bleeding between groups (RR 1.57; 95% CI 0.87-2.83; p = 0.14; I2 = 63%). In a subanalysis of patients with non-major risk factors for cardioembolism, there is no difference in recurrent stroke (RR 0.98; 95% CI 0.67-1.42; p = 0.90; I2 = 0%), all-cause mortality (RR 1.24; 95% CI 0.58-2.66; p = 0.57; I2 = 0%), and major bleeding (RR 1.00, 95% CI 0.32-3.08; p = 1.00; I2 = 0%) between groups. In patients with ESUS, DOACs did not reduce the risk of recurrent stroke, ischemic stroke or systemic embolism, or all-cause mortality. Although there was a significant increase in clinically relevant non-major bleeding, major bleeding was similar between DOACs and aspirin.

Temporal Changes in Long-Term Outcomes of Venous Thromboembolism From the Warfarin Era to the Direct Oral Anticoagulant Era.

BACKGROUND: There have been limited data on the changes in clinical outcomes after the introduction of direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) in real clinical practice. We evaluated the changes in management strategies and long-term outcomes from the warfarin era to the DOAC era. METHODS AND RESULTS: We compared the 2 series of multicenter COMMAND VTE (Contemporary Management and Outcomes in Patients With Venous Thromboembolism) registries in Japan enrolling consecutive patients with acute symptomatic VTE: Registry 1: 3027 patients in the warfarin era (2010-2014) and Registry 2: 5197 patients in the DOAC era (2015-2020). The prevalence of DOAC use increased more in Registry 2 than in the Registry 1 (Registry 1: 2.6% versus Registry 2: 79%, P<0.001). The cumulative 5-year incidence of recurrent VTE was significantly lower in Registry 2 than in Registry 1 (10.5% versus 9.5%, P=0.02), and the risk reduction of recurrent VTE in Registry 2 remained significant even after adjusting the confounders (hazard ratio [HR], 0.78 [95% CI, 0.65-0.93]; P=0.005). The cumulative 5-year incidence of major bleeding was not significantly different between the 2 registries (12.1% versus 13.7%, P=0.26), and the risk of major bleeding between the 2 registries was not significantly different even after adjusting the confounders (HR, 1.04 [95% CI, 0.89-1.21]; P=0.63). CONCLUSIONS: Along with the shift from warfarin to DOACs, there was a lower risk of recurrent VTE in the DOAC era than in the warfarin era, whereas there was no apparent change in the risk of major bleeding, which might still be an unmet need even in the DOAC era.

Direct Oral Anticoagulant Treatment for Atherosclerosis-Induced Aortic Mural Thrombus in an Elderly Male With Aspirin Resistance.

Aortic mural thrombus is associated with atherosclerosis in a vast majority of cases and could result in multiple organ damage, leading to higher morbidity and mortality rates. Although aspirin could be effective for primary prevention in atherosclerosis-induced aortic mural thrombus, aspirin resistance, which refers to the inadequate response to aspirin therapy, allows the progression of thrombus. Classically, warfarin could be an effective treatment for thromboembolic diseases, while in recent years, direct oral anticoagulants (DOACs) have shown superior safety and efficacy, particularly in elderly patients. This report presents the case of an elderly male with chronic aortic mural thrombi due to atherosclerosis and aspirin resistance who achieved favorable outcomes following treatment with DOACs. DOACs could be a possible option for managing aortic mural thrombus with aspirin resistance.