Efficacy and Safety of Low or Reduced Dose Direct Oral Anticoagulants Versus Dual Antiplatelet Therapy Following Left Atrial Appendage Closure: A Systematic Review and Meta-Analysis.

This meta-analysis aimed to compare the efficacy and safety of low-dose direct oral anticoagulants (DOACs) versus dual antiplatelet therapy (DAPT) in patients undergoing left atrial appendage closure (LAAC). A comprehensive literature search was conducted across multiple electronic databases, including PubMed, Embase, Cochrane Library, and Scopus, up to August 12, 2024. Studies comparing low-dose DOACs with DAPT in post-LAAC patients were included. The primary outcomes of interest were thromboembolic events, major bleeding, and all-cause mortality. Four studies, including two randomized controlled trials and two observational studies, met the inclusion criteria, with a total of 828 patients (319 in the DOAC group and 509 in the DAPT group). The meta-analysis revealed that patients treated with DOACs had a significantly lower risk of thromboembolic events compared to those receiving DAPT. DOACs were also associated with a significantly reduced risk of device-related thrombosis. Although the risk of stroke was lower in the DOAC group, the difference was not statistically significant. The risk of death did not differ significantly between the two groups. Regarding safety outcomes, patients receiving DOACs experienced fewer bleeding events compared to those on DAPT, with the difference being statistically significant. However, high heterogeneity was reported among the study results for bleeding events. These findings suggest that low-dose DOACs may be a more effective and safer alternative to DAPT for post-LAAC antithrombotic management, particularly in patients at high risk for both thromboembolic and bleeding events. DOACs demonstrated superior efficacy in reducing the risk of stroke, systemic embolism, and other thrombotic complications, while also minimizing bleeding risks.

Incidence of Chronic Thromboembolic Pulmonary Hypertension After Pulmonary Embolism in the Era of Direct Oral Anticoagulants: From the COMMAND VTE Registry-2.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening complication post-acute pulmonary embolism (PE). The assessment of CTEPH incidence and risk factors post-acute PE in the era of direct oral anticoagulants remains insufficient. METHODS AND RESULTS: The COMMAND VTE Registry-2 (contemporary management and outcomes in patients with venous thromboembolism registry-2) is a multicenter registry that recruited consecutive patients with acute symptomatic venous thromboembolism from 31 centers across Japan. The primary outcome was to demonstrate the detection rate of CTEPH after acute PE in routine clinical practice. Out of the 5197 patients with venous thromboembolism included in the COMMAND VTE Registry-2, 2787 were diagnosed with acute PE. Following a median follow-up duration of 747 days, 48 cases of CTEPH were detected, and the cumulative diagnosis of CTEPH in routine clinical practice was 2.3% at 3 years. Independent risk factors for the detection of CTEPH by multivariable Cox regression analysis included women (hazard ratio [HR] 2.09 [95% CI, 1.05-4.14]), longer interval from symptom onset to diagnosis of PE (each 1 day, HR 1.04 [95% CI, 1.01-1.07]), hypoxemia at diagnosis (HR 2.52 [95% CI, 1.26-5.04]), right heart load (HR 9.28 [95% CI, 3.19-27.00]), lower D-dimer value (each 1 µg/mL, HR 0.96 [95% CI, 0.92-0.99]), and unprovoked PE (HR 2.77 [95% CI, 1.22-6.30]). CONCLUSIONS: In the direct oral anticoagulant era, the cumulative diagnosis of CTEPH after acute PE was 2.3% at 3 years, and several independent risk factors for CTEPH were identified, which could be useful for screening a high-risk population after acute PE.

Rates and risk factors of bleeding after gastric endoscopic submucosal dissection with continuous warfarin or 1-day withdrawal of direct oral anticoagulants.

BACKGROUND AND AIM: The 2017 Japanese guidelines recommend continuing warfarin therapy during the perioperative period or discontinuing direct oral anticoagulants (DOACs) only on the day of endoscopic submucosal dissection for early gastric cancer. However, their safety has not been sufficiently explored. This study aimed to validate this management method. METHODS: This retrospective, multicenter study analyzed the characteristics and outcomes of patients who underwent gastric endoscopic submucosal dissection between July 2017 and June 2019. The patients were categorized according to the use of warfarin or DOACs. RESULTS: Among the 62 eligible patients, 53 (85%) were male (median age, 76 years). Warfarin was used in 10 patients (16%) and DOACs in 52 patients (84%). Fourteen patients taking DOACs (27%) used concomitant antiplatelet agents, with seven patients (13%) continuing treatment at the time of the endoscopic procedure. No postprocedural bleeding occurred in patients receiving warfarin (0%), whereas 10 cases (19%) of bleeding occurred in patients receiving DOACs: rivaroxaban, 0% (0/22); dabigatran, 0% (0/2); edoxaban, 43% (6/14); and apixaban, 29% (4/14). The type of anticoagulant (P < 0.01) and continuation of antiplatelet therapy (P = 0.02) were risk factors for postprocedural bleeding in patients receiving DOACs. Intraprocedural bleeding requiring transfusion or symptomatic thromboembolic events were not reported. CONCLUSIONS: Continuous warfarin therapy is preferred. DOAC withdrawal 1 day before a procedure is associated with a high bleeding rate, which may differ for different types of anticoagulants. The continuation of antiplatelet medications in patients receiving DOACs carries a high risk of bleeding and is a future challenge.

Cost-effectiveness analysis of direct oral anticoagulants versus low-molecular-weight heparin and no thromboprophylaxis in primary prevention of cancer-associated venous thromboembolism in China.

Background and objective: Cancer-associated venous thromboembolism (CAVTE) is a preventable, life-threatening complication with a considerable morbidity and mortality. Primary venous thromboembolism (VTE) prophylaxis is currently recommended; however, the health and economic benefits have not been evaluated and compared in China. This study aimed to assess and compare the cost-effectiveness of anticoagulants in primary CAVTE prevention among cancer patients in China. Methods: A Markov model with a 5-year horizon was established to evaluate the costs and effectiveness of direct oral anticoagulants (DOACs) compared to low-molecular-weight heparins (LMWHs) and no prevention in primary prophylaxis of CAVTE in China. Key clinical outcomes were obtained from the available clinical trials, comparing DOACs (rivaroxaban and apixaban) with LMWHs or with no thromboprophylaxis. Utility and the cost inputs were all obtained from the published literature or local data with public sources. The total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were estimated as the main endpoints of the modal for each strategy. The assessment of uncertainty was performed involving deterministic sensitivity analysis and probabilistic sensitivity analysis (PSA). Impact of time horizon, generic drug price, and individual DOACs were assessed in scenario and subgroup analyses. Results: Primary prophylaxis using DOACs were projected to yield 1.866 QALYs at a cost of $3,287.893, resulting in the ICERs of $12,895.851 (DOACs vs. no-thromboprophylaxis) and $43,613.184/QALYs (LMWHs vs. DOACs). Sensitivity analysis revealed that ICER was sensitive to the VTE and bleeding risk, drug cost of anticoagulants, self-payment ratio, and overall death rate of cancer. Probabilistic sensitivity analysis showed that DOACs and LMWHs had a 48% and 45% probability of being cost-effective at a 5-year time horizon, respectively. When the time horizon extended to 10 years, DOACs achieved a cost-effective probability of 43%. Among individual DOACs, apixaban was found to be the preferred strategy in VTE prevention due to its incremental health gain with an acceptable cost increase. Conclusion: Primary thromboprophylaxis with DOACs was cost-effective in cancer patients at a willing-to-pay (WTP) threshold of $37,125.24/QALY in China. Cancer death rate, risk of VTE and major bleeding, and the drug cost assumed greater relevance and importance in the decision-making process for primary thromboprophylaxis in cancer.

Secondary prophylaxis of venous thromboembolism (VTE) with low dose apixaban or rivaroxaban in major-thrombophilia carriers.

Direct oral anticoagulants (DOACs) are widely used for treatment and secondary prophylaxis of venous thromboembolism (VTE) and represent the gold standard for VTE secondary prophylaxis, with low-intensity DOACs administration becoming increasingly used worldwide in such scenario. Albeit widespread DOACs usage there are few literature data regarding their efficacy and safety in major thrombophilia carriers and almost no data is available for low intensity apixaban and rivaroxaban as secondary VTE prophylaxis in such patients. The aim of our study is to evaluate and confront the efficacy and safety of low-dose DOACs for VTE secondary prophylaxis, in major thrombophilia carriers vs patients at high risk of VTE recurrence for other reasons. We retrospectively evaluated patients who required long-term anticoagulant secondary prophylaxis to prevent recurrent VTE, treated with apixaban 2.5 mg BID or rivaroxaban 10 mg daily and that were screened for thrombophilia. The examined patients were 339. Baseline characteristics such as sex, age, obesity rate, smoking, number of previous VTEs and comorbidities (such as cardiovascular diseases, diabetes, mild CKD) were equally distributed in either group. The median low-dose DOACs administration time was 19.20 months (IQR 12.17-35.67). During low-dose DOACs treatment, 13 (3.8%) VTE recurrences were observed; 14 bleeding events were registered (4,1%), with no major bleeding (MB), 6 clinically relevant non major bleeding (CRNMB) (1.8%) and 8 minor bleeding (2.3%). No statistically significant difference in the rate of VTE recurrence and/or bleeding events emerged between major thrombophilia carriers and non-major thrombophilia carriers. In multivariate analysis increased risk of VTE recurrence was found for patients with cardiovascular comorbidities (HR 4.00 - p = 0.034) and for patients with more than one previous VTE episode (HR 5.14 - p = 0.034). Our data suggest that low-dose DOACs may be effective and safe in secondary VTE prophylaxis for carriers of major thrombophilia with no increase in VTE recurrence and/or bleeding risk.

Is the use of direct oral anticoagulants after non-cardiac thoracic surgery safe for patients?

PURPOSE: The outcomes of direct oral anticoagulant use after noncardiac thoracic surgery have not been elucidated. We compared the safety and efficacy of the postoperative use of direct oral anticoagulants versus warfarin. METHODS: This retrospective cohort study included patients taking anticoagulants after noncardiac thoracic surgery between 2008 and 2021. Patients were divided into 2 groups based on drug type: Group D (direct oral anticoagulants) and Group W (warfarin). The occurrence of bleeding and thromboembolic events was also assessed. RESULTS: Anticoagulants were administered to 434 postoperative patients. One (0.4%) of the 247 patients in Group D and 3 (1.6%) of the 187 patients in Group W experienced thromboembolic events. Four patients (1.6%) in Group D and 4 (2.1%) patients in Group W experienced bleeding events. All bleeding events in Group D occurred within 1 week of oral administration, whereas only 1 case of bleeding occurred after resumption in Group W. CONCLUSIONS: The outcomes of patients treated with direct oral anticoagulants did not differ from those of patients treated with warfarin. However, major bleeding can occur after the postoperative resumption of direct oral anticoagulant use. Attention should be paid to resuming oral anticoagulants within a few days of non-cardiac thoracic surgery.

Direct oral anticoagulants (DOACs) for postoperative venous thromboembolism prophylaxis in patients with gynecologic malignancies: A quality mini-review.

Venous thromboembolism (VTE) is a common cause of morbidity and mortality in gynecologic oncology patients with an increased risk in the postoperative period. Historically, international guidelines have recommended 28 days of low molecular weight heparin (LMWH) or unfractionated heparin (UFH) for extended VTE prophylaxis after major abdominal and pelvic surgery for gynecologic malignancies. Direct oral anticoagulants (DOACs) have emerged as an attractive alternative to injectable anticoagulants. This quality mini-review evaluated the literature around the use of DOACs for postoperative VTE prophylaxis after surgery for gynecologic cancer. Overall, the reviewed literature supports the use of DOACs in select patients within this population which may lead to an improved patient experience, higher rates of treatment compliance, and increased cost savings.

Predictors of recurrent venous thromboembolism and major bleeding in patients with cancer: A secondary analysis of the CANVAS trial.

INTRODUCTION: Patients with cancer have an increased risk of developing venous thromboembolism (VTE) but also have an increased risk of both recurrent VTE and bleeding with anticoagulation compared to anticoagulated patients without cancer. CANVAS, a randomized pragmatic effectiveness trial, compared the direct oral anticoagulants a class to low molecular weight heparin for treatment of a new VTE in patients with cancer. The aim of this prespecified secondary analysis of the CANVAS trial is to identify predictors of both recurrent VTE and major bleeding in patients with cancer and new VTE. METHODS: Data from the 671 participants in the analysis population were used to identify predictors of recurrent VTE and bleeding during the 6-month treatment period. Significant predictors identified in the univariable models were carried forward in the multivariable models to identify independent predictors of both risks. RESULTS: Independent predictors of recurrent VTE include ECOG performance status ≥2 (HR, 3.19 [95 % CI, 1.45-7.02]; P < .005), presence of metastatic disease (HR, 2.57 [95 % CI, 1.14-5.80]; P = .023), treatment with bevacizumab (HR, 2.50 [95 % CI, 1.04-5.99]; P = .041), and deep vein thrombosis without pulmonary embolus as index VTE (HR, 1.86 [95 % CI, 1.04-3.33]; P = .037). Independent predictors of major bleeding include serum albumin <3.5 g/dL (HR 1.97 [95 % CI, 1.02-3.79]; P = .044) and metastatic disease (HR 2.80 [95 % CI, 1.08-7.22]; P = .034). CONCLUSION: Findings from this pre-specified analysis of the CANVAS trial identified risk factors for recurrent VTE and major bleeding in a population of participants with cancer and new VTE that reflect current oncology clinical practice. Results can be used to identify at risk patients in practice and inform new risk prediction models to improve the care of these patients.

Safety of Sofosbuvir-Based Direct-Acting Antivirals for Hepatitis C Virus Infection and Direct Oral Anticoagulant Co-Administration.

Background: Direct oral anticoagulants (DOACs) are recommended for the management of thrombosis prophylaxis, especially in patients with atrial fibrillation. As substrates of cytochrome P450 (CYP) 3A4 and/or P-glycoprotein, they are implicated in potential drug-drug interactions. NS5A/NS5B inhibitors are direct-acting agents (DAAs) against the Hepatitis C Virus (HCV) infection that exert a mild inhibition of P-glycoprotein without effects on CYP3A4. A DOAC and NS5A/NS5B inhibitor co-administration may lead to an increased risk of bleeding. Real-world data on the concomitant use of DOACs and DAAs are scarce. On this purpose, we perform a retrospective analysis on the risk of vascular adverse events (bleeding and thrombosis) among HCV patients under DOAC/DAA therapy, even in advanced liver disease. Methods: Between May 2015 and April 2023, patients treated with sofosbuvir-based DAA regimens and DOACs were consecutively included in this study from 12 Italian medical centers. Baseline characteristics, especially concerning bleeding risk and liver function, were collected. The occurrence of bleeding events, classified as major and minor, was the primary endpoint. Secondary endpoints were the rate of any thrombotic events and/or the need for discontinuation of one or both treatments. Moreover, a cohort of patients, matched by demographic characteristics (age and sex), that switched to vitamin K antagonists (VKAs) during the antiviral treatment was compared with the DOAC/DAA group. Results: A total of 104 patients were included. Thirty-eight of them (36.5%) were cirrhotic. Atrial fibrillation was an indication for anticoagulation in almost all cases (76%). Rivaroxaban (35.6%) was the most used DOAC, followed by apixaban (26.9%), dabigatran (19.2%) and edoxaban (18.3%). Sofosbuvir/velpatasvir (78.8%) was the most prescribed DAA, and all patients were already on anticoagulant therapy before the start of DAAs. During concomitant DOAC/DAA treatment, no major bleeding events were recorded, while four minor bleeding events occurred, but none resulted in DAA or DOAC discontinuation. At univariate analysis, the only additional risk factor statistically related to bleeding events was the anticoagulant therapy (hazard ratio [HR]: 13.2, 95% confidence interval 1,6-109). Performing an evaluation by a LOGIT binomial analysis with demographic characteristics, the antiplatelet therapy remained statistically associated to bleeding events. No significant differences were found in the rate of clinically relevant bleeding when the main population was compared with the VKA-switched cohort. A single major bleeding event leading to anticoagulation and DAA discontinuation was reported in VKA-switched matched cohort. Conclusions: In our study, the concomitant use of NS5A/NS5B inhibitors with DOAC showed good safety, and the only risk factor associated with bleeding events was the concomitant antiplatelet therapy. These findings support the use of DOACs during sofosbuvir-based HCV treatment, even in advanced liver disease. Replacing DOACs with VKAs does not appear to be of clinical benefit.

Exploring bleeding in oral anticoagulant users: assessing incidence by indications and risk factors in the entire nationwide cohort.

Background: Oral anticoagulants (OACs) are essential for the prevention and treatment of thromboembolic disorders, but bleeding, a major complication, can have a fatal impact on the patient's treatment. Objectives: We aimed to estimate the nationwide, real-world incidence rate of bleeding in patients taking OACs and confirm the incidence by indications and risk factors. Methods: This cross-sectional study identified OAC users from April 1 to December 31, in both 2019 and 2020, using the HIRA-NPS database. The primary outcome variables were the incidence rate of major bleeding events during OAC treatment and within 30 days of treatment discontinuation. We estimated the adjusted incidence rate ratio (aIRR) in subpopulations. Results: Among 18,822 OAC users, the incidence rate of major bleeding was 27.9 (95% CI: 24.6-31.5) per 1,000 person-years. The incidence rate of major bleeding was higher in patients with a bleeding history, with an aIRR of 11.51; those at high bleeding risk (HAS-BLED score ≥3), with an aIRR of 1.51; those with high CCI scores ≥3, with an aIRR of 1.88; and those with liver disease, with an aIRR of 1.41. For indications, compared to patients with nonvalvular atrial fibrillation (NVAF), the aIRR of major bleeding was significantly higher at an aIRR of 2.35 in patients undergoing VTE treatment. Patients with ischemic stroke showed a higher incidence of major bleeding with an aIRR of 2.13 than NVAF patients. The aIRR of major bleeding in the oral anticoagulant group, compared to the matched control group, was 2.25 (95% CI: 1.93-2.63). Conclusion: These findings may be useful for implementing strategies to improve the evaluation and management of anticoagulation-related bleeding.

Stroke severity and outcomes in patients with intracerebral hemorrhage on anticoagulants and antiplatelet agents: An analysis from the Japan Stroke Data Bank.

BACKGROUND AND AIM: Some patients with intracerebral hemorrhage are on antithrombotic agents at the time of the event and these may worsen outcome, but the relative risk of different oral anticoagulants and antiplatelet agents is uncertain. We determined associations between pre-onset intake of antithrombotic agents and initial stroke severity, and outcomes, in patients with intracerebral hemorrhage. METHODS: Patients with intracerebral hemorrhage admitted within 24 h after onset between January 2017 and December 2020 and recruited to the Japan Stroke Data Bank, a hospital-based multicenter prospective registry, were included. Enrolled patients were classified into four groups based on the type of antithrombotic agents being used on admission. The outcomes were the National Institutes of Health Stroke Scale (NIHSS) score on admission and modified Rankin Scale (mRS) of 5-6 at discharge. RESULTS: Of a total 9810 patients with intracerebral hemorrhage (4267 females; mean age = 70 ± 15 years), 77.1% were classified into the no-antithrombotic group, 13.2% into the antiplatelet group, 4.0% into the warfarin group, and 5.8% into the direct oral anticoagulant (DOAC) group. Median (interquartile range) NIHSS score on admission was 12 (5-22), 13 (5-26), 15 (5-30), and 13 (6-24), respectively, in the four groups. In multivariable analysis, the prestroke warfarin use was associated with higher NIHSS score (adjusted incidence rate ratio = 1.09 (95% confidence interval (CI) = 1.06-1.13), with the no-antithrombotic group as the reference), but the antiplatelet group (1.00 (95% CI = 0.98-1.02)) and DOAC group (0.98 (95% CI = 0.95-1.01)) were not. The rate of mRS 5-6 at discharge was 30.8%, 41.9%, 48.6%, and 41.5%, respectively, in the four groups. In multivariable analysis, prestroke warfarin use was associated with mRS 5-6 (adjusted odds ratio = 1.90 (95% CI = 1.28-2.81), with the no-antithrombotic group as the reference), but the antiplatelet group (1.12 (95% CI = 0.91-1.37)) and DOAC group (1.25 (95% CI = 0.88-1.77)) were not. CONCLUSION: Patients who were taking warfarin prior to intracerebral hemorrhage onset suffered more severe intracerebral hemorrhage as evidenced by higher admission NIHSS and higher discharge mRS. In contrast, no increase in severity was seen with antiplatelet agents.

Management and outcomes in patients with tumor thrombus: A retrospective cohort study.

BACKGROUND: Tumor thrombus can be associated with an increased risk of venous thromboembolism (VTE) and poor prognosis. The risks and benefits of anticoagulation remain unclear. METHODS: We conducted a single-center retrospective cohort study in patients with tumor thrombus in 2019-2022. All patients were followed for 12 months from the diagnosis of tumor thrombus or until death if death occurred earlier. The primary outcome was the percentage of patients prescribed any dose of anticoagulation for tumor thrombus (or concurrent bland thrombus/VTE). The secondary outcomes included new thrombosis, major bleeding (MB), clinically relevant non-major bleeding (CRNMB), and mortality. We calculated the 6- and 12-month cumulative incidence of outcomes with 95% confidence interval (CI) and compared those given anticoagulation versus not, considering death as a competing risk. RESULTS: We included 211 patients, among whom 106 (50.2%) (95% CI: 47.9-52.6) were given anticoagulation for tumor thrombus or concurrent VTE (present in 21.8%). The most common type of cancer was hepatocellular carcinoma (28%). Splanchnic veins were the most commonly involved (49.3%). Anticoagulation was more likely used if tumor thrombus involved the inferior vena cava, the heart, with concurrent VTE, or if thrombosis service was consulted. The overall 12-month incidence of new VTE was 11.4% (95% CI 7.3-16.5), that of MB + CRNMB was 36.6% (95% CI 29.6-43.5), and mortality of 52.5% (95% CI 44.8-59.6), with no significant differences among groups given anticoagulation or not. CONCLUSIONS: Patients with tumor thrombus carry high risks of VTE, bleeding and mortality. The impact of anticoagulation remains unclear.

Bleeding Complications of Anticoagulation Therapy in Clinical Practice-Epidemiology and Management: Review of the Literature.

Due to their very wide range of indications, anticoagulants are one of the most commonly used drug groups. Although these drugs are characterized by different mechanisms of action, the most common complication of their use is still bleeding episodes, the frequency of which depends largely on the clinical condition of the patient using such therapy. For this reason, to this day, the best method of preventing bleeding complications remains the assessment of bleeding risk using scales such as HAS-BLED. There are many reports in the literature assessing the occurrence of this type of complication after the use of drugs affecting the coagulation process, as well as many reports comparing individual groups of drugs with different mechanisms of action. However, there are still no clear guidelines that would indicate which group of anticoagulants should be preferred in particular groups of patients. The aim of our article is to summarize the data collected so far regarding the safety of using specific groups of anticoagulants and the frequency of bleeding complications after their use.

Evaluating the Risk of Traumatic Brain Injury in Adults Following a Fall With Concomitant Use of Anti-Coagulation: A Retrospective Cohort Study.

Introduction Falls and fractures are major health challenges for older adults in England. Despite the advantages of anticoagulants, their use in the elderly is often restricted due to concerns about fall-related injuries. However, there is a lack of clear data on the risk of discontinuing anticoagulation therapy solely due to fall risk. NICE guidelines (2021) advise that anticoagulation should not be withheld solely based on age or fall risk. This study aims to assess the incidence of significant brain injuries or intracranial haemorrhages in patients on anticoagulant therapy, also comparing the independent risk factors for traumatic brain injury. Objective This study aims to assess the incidence of TBI following falls in patients on anticoagulant therapy, comparing outcomes between those using DOACs and Vitamin K antagonists. Methods A retrospective cohort study was conducted at Queen Alexandra Hospital, University Hospitals Portsmouth NHS Trust, from November 2023 to May 2024. Data were collected from 3,468 CT head scans performed on patients with a history of falls, including 801 on anticoagulation therapy. Results Of the 801 patients on anticoagulation, 763 (95.2%) were aged 65 or older, with a mean age of 83.1 years. Acute hemorrhage was detected in 3.1% (25/801) of patients. Patients on Warfarin and Dabigatran had significantly higher TBI risk compared to those on Apixaban (6.7%, p=0.02; and 7.6%, p=0.01, respectively), while Edoxaban and Rivaroxaban showed no significant difference. Also, older age (≥65 years) and higher frailty scores (CFS 6 and 7) were associated with increased TBI risk (p<0.05). All patients with acute hemorrhage received conservative management, and two patients experienced mortality within six months.  Discussion The study indicates that the risk of TBI following falls in anticoagulated patients is 3.1% relatively low, aligning with existing literature. This underscores the need for careful consideration before discontinuing anticoagulation therapy solely based on fall risk. Hence, discontinuation of anticoagulation should be a patient-specific decision that carefully considers the balance between the risk of traumatic brain injury (TBI) and the benefits of anticoagulation therapy. Factors such as age, frailty, and the type of anticoagulant should all be taken into account. Clinical judgment and selective CT imaging can help balance patient safety with healthcare costs.  Conclusion The incidence of adverse outcomes following head injury in patients on anticoagulant therapy is 3.1% and relatively low. Careful decision-making regarding the discontinuation of anticoagulation therapy, informed by patient background and presentation and selective CT imaging, is essential to manage risks effectively and optimize healthcare resource utilization.

Perioperative Elective Management in Patients Treated with Direct Oral Anticoagulants - Practical Guide.

<b>Introduction:</b> Despite clear, relatively easy-to-use guidance, many clinicians find the perioperative management of direct oral anticoagulants (DOACs) challenging. Inappropriate antithrombotic management can delay procedures and lead to bleeding or thromboembolic complications.<b>Aim:</b> We aimed to describe perioperative management practices related to planned procedures regarding DOACs in accordance with the applicable guidelines of cardiological and surgical societies.<b>Results:</b> Perioperative management of DOAC therapy depends on many factors, and recommendations in the guidelines are not consistent.<b>Conclusions:</b> The best approach to managing these patients is therefore to strike a balance between the risks of bleeding and thromboembolism.

Gastrointestinal bleeding among oral anticoagulant users: a comprehensive 7-year retrospective review using Türkiye's national health data system.

Background/aim: The comparative risk of gastrointestinal bleeding (GIB) among users of direct-acting oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) is a topic of ongoing debate. This study leverages a comprehensive national health database to evaluate the incidence of GIB, associated risk factors, and postbleeding management strategies among anticoagulated patients. Materials and methods: Utilizing the Turkish Ministry of Health's e-Nabiz system, we conducted a retrospective analysis of patients treated with DOACs and warfarin from January 2017 to July 2023. GIB events were identified using ICD codes, and comorbidities, prior medication use, interventions, and mortality rates were analyzed. Drug survival and patterns of changes following GIB were also evaluated. Results: Among 102,545 patients with a GIB event during anticoagulant treatment, DOAC users were older with a higher prevalence of comorbidities, except for chronic obstructive lung disease, compared to VKA users. GIB-related mortality was 0.6% in the DOAC group and 0.4% in the VKA group at admission after the GIB (p < 0.01). In all drug groups, approximately half of the patients discontinued anticoagulation due to GIB after 3 months, the rate being highest with apixaban (61.9%). In patients who continued anticoagulation, the anticoagulant prior to GIB remained the most common agent in all groups, with rivaroxaban having the highest retention rate (40.7%). Conclusion: This nationwide study indicates a higher frequency of GIB in DOAC users versus VKA users, with age and comorbidities potentially contributing to this trend. Mortality rates were comparable to the previous literature but warrant further investigation. The significant rate of discontinuation following GIB raises concerns about ongoing anticoagulation management. These findings underscore the need for cautious case management.

Safety and Effectiveness of Oral Anticoagulants in Atrial Fibrillation: Real-World Insights Using Natural Language Processing and Machine Learning.

Background/Objectives: We assessed the effectiveness and safety of vitamin K antagonists (VKAs) versus direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) using artificial intelligence techniques. Methods: This is a retrospective study in 15 Spanish hospitals (2014-2020), including adult AF patients with no history of anticoagulation, thrombosis events, rheumatic mitral valvular heart disease, mitral valve stenosis, or pregnancy. We employed EHRead® technology based on natural language processing (NLP) and machine learning (ML), along with SNOMED-CT terminology, to extract clinical data from electronic health records (EHRs). Using propensity score matching (PSM), the effectiveness, safety, and hospital mortality of VKAs versus DOACs were analyzed through Kaplan-Meier curves and Cox regression. Results: Out of 138,773,332 EHRs from 4.6 million individuals evaluated, 44,292 patients were included, 79.6% on VKAs and 20.4% on DOACs. Most patients were elderly [VKA 78 (70, 84) and DOAC 75 (66, 83) years], with numerous comorbidities (75.5% and 70.2% hypertension, 47.2% and 39.9% diabetes, and 40.3% and 34.8% heart failure, respectively). Additionally, 60.4% of VKA and 48.7% of DOAC users had a CHA2DS2-VASc Score ≥4. After PSM, 8929 patients per subgroup were selected. DOAC users showed a lower risk of thrombotic events [HR 0.81 (95% CI 0.70-0.94)], minor bleeding [HR 0.89 (95% CI 0.83-0.96)], and mortality [HR 0.80 (95% CI 0.69-0.92)]. Conclusions: Applying NLP and ML, we generated valuable real-world evidence on anticoagulated AF patients in Spain. Even in complex populations, DOACs have demonstrated a better safety and effectiveness profile than VKAs.

Real-world evidence of direct oral anticoagulants in patients with atrial fibrillation and cancer: A meta-analysis.

Background: Several observational cohort studies have been conducted to investigate the effectiveness and safety of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) in patients who have both atrial fibrillation (AF) and cancer. Herein, we conducted a meta-analysis to present a comprehensive overview of the real-world evidence on DOACs in patients with AF and cancer. Methods: A comprehensive search strategy was performed in PubMed and Embase until February 2024 for studies that enrolled AF patients with cancer who received DOACs or VKAs. The adjusted risk ratios (RRs) and 95% confidence intervals (CIs) of each outcome were extracted and pooled by a random-effects model. Results: Seven observational cohort studies were eligible for data extraction. The random-effects model analysis indicated that compared with VKA use, the use of DOACs was significantly associated with reduced risks of stroke or systemic embolism (RR=0.79, 95 % CI 0.64---0.97), major bleeding (RR=0.84, 95 % CI 0.71---0.99), intracranial bleeding (RR=0.61, 95 % CI 0.54---0.69), and gastrointestinal bleeding (RR=0.87, 95 % CI 0.80---0.95) in AF patients with concurrent cancer. Conclusions: Compared with VKAs, the use of DOACs was associated with decreased risks of thrombotic and bleeding events in AF patients with cancer. Data from real-world scenarios support the use of DOACs as a favorable treatment option for this specific patient population.

Appropriateness of direct oral anticoagulant dosing in patients with atrial fibrillation at a tertiary care hospital in Thailand.

Background: Appropriate dosing of direct oral anticoagulants (DOACs) has been associated with clinical efficacy and safety. Several studies have shown that DOAC dosing are often inconsistent with guideline recommendations. Little is known about this issue in Thailand. This study aimed to evaluate the appropriateness of DOAC dosing in Thai hospitalized patients with atrial fibrillation (AF). Method: This was a retrospective descriptive study conducted on hospitalized patients at Rajavithi Hospital, a tertiary care hospital in Thailand. Inpatients diagnosed with AF and treated with DOACs between February 2021 and February 2023 were enrolled in the study. The appropriate dosing of DOACs was assessed according to the recommendation of the 2021 European Heart Rhythm Association Practical Guide on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation (EHRA). Descriptive statistics were used to analyze the data; median (interquartile range) for continuous variables, and numbers and percentages for categorical variables. Results: A total of 120 patients with AF were evaluated for dosing. The patients received rivaroxaban in 47 cases (39.2 %), apixaban in 32 cases (26.7 %), edoxaban in 31 cases (25.8 %), and dabigatran in 10 cases (8.3 %). Most of the patients were elderly, with a median age of 77.5 (68-84) years. Females were predominant (57.5 %). Our findings indicate that the prevalence of appropriate dosing of DOACs was 63.3 %. However, approximately one-third of patients received inappropriate dosing, with 24 (20.0 %) being overdosed, and 20 (16.7 %) being underdosed. The highest overdosing and underdosing rates were seen in dabigatran (90.0 %) and apixaban (21.9 %), respectively. Conclusion: Inappropriate dosing of DOACs according to the 2021 EHRA recommendations was high in 36.7 %, with overdosing mostly occurring in 20.0 %. The high number of inappropriate dosing highlights the need for implementation of optimal strategies to select the appropriate dose of DOACs in Thai hospitalized patients with AF.