Search

Background: The ability of bleeding risk scores to predict major bleeding (MB) or clinically relevant nonmajor bleeding (CRNMB) remains a topic of contention, particularly in nonselected patients in family practice. In addition, the capacity to predict bleeding risk using simple variables has yet to be established., Objectives: The main objective was to confirm that severe anemia was the most predictive factor for the estimation of bleeding risk in patients treated with vitamin K antagonists (VKAs). Secondary objectives were to test the capacity of different bleeding scores to detect high-risk patients. Subsequently, the impact of functional decline on bleeding incidence was explored., Methods: The CACAO study was a multicenter prospective cohort study of patients who, due to nonvalvular atrial fibrillation (NVAF) and/or venous thromboembolism (VTE), had been prescribed an oral anticoagulant by their general practitioner (GP) as a prophylactic measure. Patient characteristics were collected at the time of inclusion by GPs, who then monitored them in accordance with standard practice for one year. MB and CRNMB were the main outcomes for one year. By applying this approach, a total of 13 scores were analyzed., Results: Aaemia was found to be strongly associated with MB (HR: 2.77, 95% CI: 1.2-6.36), with a particularly pronounced association observed in cases of severe anemia (HR: 12.9, 95% CI: 2.76-60.35). Twelve out of 27 MB cases were not identified by at least half of the scores. By contrast, functional decline was identified as a novel factor associated with MB (HR: 2.45, 95% CI: 1.13-5.31)., Conclusions: Preexisting anemia is a major prognostic factor associated with the occurrence of bleeding. It seems relevant to suggest that functional decline should be considered by GPs when assessing bleeding risk., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

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.

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., (© 2024 The Author(s). Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Objective: We aimed to evaluate the safety and efficacy of antithrombotic strategies by age in patients with atrial fibrillation and acute coronary syndrome and/or percutaneous coronary intervention in AUGUSTUS., Methods: Patients were stratified into 3 age groups: <65, 65-74, and ≥75 years. Outcomes of interest were major or clinically relevant non-major bleeding, major bleeding, death or rehospitalization, and ischemic events. Treatment effects of apixaban vs. vitamin K antagonist (VKA) and aspirin vs. placebo were assessed across age groups using Cox models., Results: Of 4614 patients, 1267 (27.5%) were <65, 1802 (39.0%) were 65-74, and 1545 (33.5%) were ≥75 years. Apixaban was associated with lower rates of major or clinically relevant non-major bleeding than VKA (<65: HR 0.69 [0.47-1.00]; 65-74: HR 0.57 [0.43-0.75]; ≥75: HR 0.81 [0.63-1.04]). Death or hospitalization occurred less often with apixaban, regardless of age. No differences were observed in rates of ischemic events between apixaban and VKA according to age. Aspirin was associated with higher rates of bleeding than placebo (<65: HR 1.67 [1.15-2.43]; 65-74: HR 2.32 [1.73-3.10]; ≥75: HR 1.69 [1.31-2.19]). Rates of death or rehospitalization and ischemic events were similar among patients receiving aspirin or placebo across age groups., Conclusions: Apixaban was associated with greater absolute reduction in bleeding than VKA in older age groups, reflecting their higher hemorrhagic risk. Aspirin increased bleeding in all age groups vs. placebo. Our findings support the use of apixaban plus a purinergic receptor P2Y 12 (P2Y 12 ) inhibitor without aspirin in patients with atrial fibrillation and recent acute coronary syndrome/percutaneous coronary intervention, regardless of age., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The optimal approach for anticoagulation in patients with bioprosthetic valves and atrial fibrillation (AF) remains a subject of debate. A meta-analysis using updated evidence to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) compared to vitamin K antagonists (VKAs) in patients with AF and bioprosthetic valves to address this controversy., Methods: A comprehensive search was conducted in multiple databases, including PubMed, Scopus, Web of Science, ProQuest, and the Cochrane Central Register of Controlled Trials, up until March 2023. The search aimed to identify relevant randomized controlled trials (RCTs) that examined the efficacy and safety outcomes of both direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with bioprosthetic valves and atrial fibrillation. The primary outcomes of interest were major bleeding and all-cause mortality., Results: Our study demonstrated that despite the difference was not significant, the hazard of all-cause mortality was 2.5% higher in the DOAC group (HR = 1.03, 95% CI = [0.88, 1.19], p-value = .75). Similarly, the hazard of stroke (HR = 1.03, 95% CI = [0.87, 1.32], p-value = .71) and major bleeding (HR = 1.11, 95% CI = [0.89, 1.38], p-value = .36) were found to be respectively 3.2 and 10.7% higher in the DOAC group, although the difference was not significant. However, the hazard of intracranial hemorrhage was found to be 28.8 lower in the DOAC treatment group (HR = 0.71, 95% CI = [0.39, 1.31], p-value = .27), which again was not statistically significant., Conclusions: Our meta-analysis demonstrates that in patients undergoing bioprosthetic valve surgery and presenting with AF afterward, DOAC and VKA are similar regarding life-threatening and all-cause mortality outcomes, including major bleeding, stroke, and intracranial hemorrhage., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The efficacy and safety of direct oral anticoagulants (DOACs) versus warfarin in patients with antiphospholipid syndrome-associated venous thromboembolism (APS-VTE) remain uncertain. We aimed to evaluate efficacy and safety of DOACs in patients with APS-VTE., Methods: Using the Korean Health Insurance Review and Assessment Service database, we retrospectively identified all APS-VTE cases. We examined the VTE recurrence, arterial thrombosis, death and bleeding in patients who received DOACs compared with warfarin for therapeutic anticoagulation., Results: Of all the VTE cases (n = 84,916) detected between 2014 and 2018, patients with APS-VTE (n = 410) accounted for 0.48%. Most patients with APS-VTE (73%) were aged < 60 years. The recurrent VTE occurred in 8 of 209 patients (3.8%) who received DOACs and in 7 of 201 (3.5%) who received warfarin (relative risk [RR], 1.099; 95% confidence interval [CI], 0.41-2.98; P = 1.000). The arterial thrombosis (ATE) occurred in 8 of 209 patients (3.8%) who received DOAC and in 20 of 201 (10%) who received warfarin (RR, 0.385; 95% CI, 0.17-0.85; P = 0.024). The composite outcomes of VTE recurrence, ATE, or mortality were significantly lower in patients (9.1%) on DOAC than in those (16.3%) on warfarin (RR, 0.537; 95% CI, 0.32-0.91; P = 0.028). The bleeding outcome occurred in 7 of 209 (3.4%) patients in the DOACs group and 7 of 201 (3.5%) patients in the warfarin group (RR, 0.96; 95% CI, 0.34-2.69; P = 0.840)., Conclusion: In patients with APS-VTE, DOACs group showed comparable rates of recurrent VTE, bleeding, and deaths, but a significantly lower incidence of ATE and composite outcomes compared with the warfarin group in Korea., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

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., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Patients on systemic oral anticoagulation with vitamin K antagonists (VKA) or non-vitamin K oral anticoagulants (NOAC) often require triple therapy following percutaneous coronary intervention, substantially increasing the risk of bleeding. Gastroprotective agents like proton pump inhibitors (PPI) are often employed to mitigate this risk, despite potential competitive inhibition between P2Y12-receptor inhibitors, NOACs, and VKAs. While the interactions and clinical outcomes of PPIs and DAPT have been frequently explored in literature, not many studies have evaluated the same outcomes for triple therapy., Areas Covered: This comprehensive narrative review of three studies on PPIs and triple from the PubMed/MEDLINE database supplemented by 23 other relevant studies aims to use the available literature to analyze the potential interactions between PPIs and triple therapy while shedding light on their mechanisms, clinical implications, and areas for optimization., Expert Opinion: If triple therapy is indicated following PCI, then patients at high-risk for bleeding may benefit from transition to apixaban and a PPI to lower the risk of gastrointestinal bleeding. More research is needed to determine the role of PPIs in triple therapies in prevention of gastrointestinal bleeding or potentiation of other adverse outcomes.

Introduction: We previously conducted a prospective, observational post-marketing surveillance study to assess the safety and effectiveness of four-factor prothrombin complex concentrate (4F-PCC) for rapid vitamin K antagonist (VKA) reversal in Japanese patients., Methods: This subgroup analysis compared the safety, especially thromboembolic events (TEEs), and effectiveness of 4F-PCC by stratifying patients into two subgroups according to baseline international normalized ratio (INR) levels with < 2.0 and ≥ 2.0., Results: Of 1271 eligible patients, 215 (17.9%) had INR < 2.0 and 987 (82.1%) had INR ≥ 2.0. Overall baseline characteristics were similar between groups; age (74.0 years vs 74.0 years), body mass index (22.1 kg/m 2 vs 21.9 kg/m 2 ), ratio of inpatients (90.2% vs 88.7%), manifested atrial fibrillation (46.0% vs 48.8%). Median INRs at baseline were 1.72 (minimum 0.92, maximum 1.99) in the INR < 2.0 group and 2.95 (2.00, 27.11) in the INR ≥ 2.0 group. The most common reason for 4F-PCC administration was intracranial hemorrhage (67.0% vs 59.5%), and lesser gastrointestinal bleeding (0.9% vs 7.5%). After 4F-PCC administration (average doses 24.5 IU/kg [INR < 2.0 group] and 29.2 IU/kg [INR ≥ 2.0 group]), INRs were significantly reduced to 1.21 (- 28%) and 1.31 (- 68%), respectively, and resulted in hemostasis in a similarly rapid manner. The incidences of adverse drug reactions were 3.7% in each group. TEEs occurred in 4 (1.9%) patients in the INR < 2.0 group and 11 (1.1%) patients in the INR ≥ 2.0 group and were predominantly composed of stroke, while similar rates (67.0% vs 62.9%) of bleeding events post-anticoagulant resumption were observed between groups., Conclusion: This study supports the favorable tolerability and efficacy of 4F-PCC regardless of baseline INR (< 2.0 or ≥ 2.0), with a prompt reduction of INR and substantial hemostatic effectiveness in the real-world setting for patients requiring urgent VKA reversal, although no indicated 4F-PCC dose for VKA reversal exists for INR < 2.0 to date., (© 2024. The Author(s).)

Background: As direct oral anticoagulants (DOACs) have become widely recommended as first-line anticoagulation therapy, patients who remain on warfarin are likely those unable to afford, adhere to, or utilize DOAC therapy due to the presence of a contraindication. It is currently unknown how availability of DOACs have affected populations being managed at warfarin (VKA) anticoagulation clinics. Methods: This was a retrospective chart review assessing warfarin-treated patients at an outpatient anticoagulation clinic. The primary endpoint was the 6-month time in therapeutic range (TTR) before and after DOACs were recommended as first-line therapy by clinical guidelines. Study periods were January to June 2015, before DOACs were recommended over VKA, and January to June 2022, when DOACs were often recommended over VKA. TTR, demographic changes, and the presence of contraindications to DOAC therapy in the clinic population between the two time periods were assessed. Results: No difference in 6-month TTR was observed between study periods (59% in 2015 vs 63% in 2022; P = .45). Patient demographics did not significantly vary, which may be due to the clinic retaining 45% of patients between both time periods. Contraindications to DOAC therapy were identified in 39% of the 2015 group and 49% of the 2022 group ( P = .18). The most common contraindication was indication for anticoagulation. Conclusion: Availability of DOACs did not seem to significantly affect the population or management of warfarin-treated patients at an outpatient anticoagulation clinic, however, contraindications and potential challenges to use of DOAC therapy are present in many patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The impact of chronic oral anticoagulant (OACs) use on long-term post-discharge outcomes after coronavirus disease 2019 (COVID-19) hospitalisation remains unclear. Herein, we compared clinical outcomes up to 2-years after COVID-19 hospitalisation between patients on vitamin K antagonists (VKAs), direct-acting OACs (DOACs) and no OAC therapy., Methods: Data from TriNetX, a global federated health research network, were used. Adult patients on VKAs, DOACs or no OAC therapy at diagnosis of COVID-19 between 20 January 2020 and 31 December 2021, who were hospitalised for COVID-19, were included. The primary outcomes were all-cause mortality, ischaemic stroke/transient ischaemic attack (TIA)/systemic embolism (SE) and the composite of intracranial haemorrhage (ICH)/gastrointestinal bleeding, at 2 years after COVID-19 hospitalisation., Results: We included 110,834 patients with COVID-19. Following propensity score matching (PSM), we identified a decreased mortality risk in DOAC-treated patients compared to the no OAC cohort (RR .808, 95% CI .751-.870). A higher risk of ischaemic stroke/TIA/SE was observed in VKA users compared to DOAC users (RR 1.100, 95% CI 1.020-1.220) and in VKA users compared to patients not taking OAC (RR 1.400, 95% CI 1.140-1.720). VKA use was associated with a greater risk of ICH/gastrointestinal bleeding than DOAC users (RR 1.198, 95% CI 1.066-1.347), while DOAC users had a lower risk compared to no OAC-treated patients (RR .840, 95% CI .754-.936)., Conclusion: COVID-19 patients taking prior DOACs were associated with lower long-term mortality risk and ICH/gastrointestinal bleeding than patients not taking OAC. Compared to patients on DOACs, VKA users were associated with higher risks of mortality, ischaemic stroke/TIA/SE and ICH/gastrointestinal bleeding., (© 2024 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Introduction: Rheumatic heart disease with persistent atrial fibrillation (RHD-AF) is associated with increased morbidity. However, there is no standardized approach for the maintenance of sinus rhythm (SR) in them. We aimed to determine the utility of a stepwise approach to achieve SR in RHD-AF., Methods: Consecutive patients with RHD-AF from July 2021 to August 2023 formed the study cohort. The stepwise approach included pharmacological rhythm control and/or electrical cardioversion (Central illustration). In patients with recurrence, additional options included AF ablation or pace and ablate strategy with conduction system pacing or biventricular pacing. Clinical improvement, NT-proBNP, 6-Minute Walk Test (6MWT), heart failure (HF) hospitalizations, and thromboembolic complications were documented during follow-up., Results: Eighty-three patients with RHD-AF (mean age 56.13 ± 9.51 years, women 72.28%) were included. Utilizing this approach, 43 (51.81%) achieved and maintained SR during the study period of 11.04 ± 7.14 months. These patients had improved functional class, lower NT-proBNP, better distance covered for 6MWT, and reduced HF hospitalizations. The duration of AF was shorter in patients who achieved SR, compared to those who remained in AF (3.15 ± 1.29 vs 6.93 ± 5.23, p = 0.041). Thirty-five percent (29) maintained SR after a single cardioversion over the study period. Only one underwent AF ablation. Of the 24 who underwent pace and ablate strategy, atrial lead was implanted in 22 (hybrid approach), and 50% of these achieved and maintained SR. Among these 24, none had HF hospitalizations, but patients who maintained SR had further improvement in clinical and functional parameters., Conclusions: RHD-AF patients who could achieve SR with a stepwise approach, had better clinical outcomes and lower HF hospitalizations., (© 2024 Wiley Periodicals LLC.)

Non-activated four-factor prothrombin complex concentrate (4 F-PCC) has emerged as the preferred reversal strategy for patients on warfarin with life-threatening bleeding. Current dosing recommendations for 4 F-PCC require pre-treatment international normalized ratio (INR) and bodyweight values, resulting in ordering and administration delays. Studies have shown that alternative dosing regimens are safe and efficacious. This retrospective, single-center, pre- and post-protocol analysis was conducted to assess the efficacy of a pharmacist driven modified fixed-dose 4 F-PCC regimen versus package insert weight- and INR-based dosing regimen for warfarin reversal. The primary outcome was achievement of INR less than two. Secondary outcomes included dose and cost of 4 F-PCC, a time analysis, incidence of concomitant vitamin K administration, and incidence of thrombosis within seven days of 4 F-PCC. There were 195 patients included in the analysis, with 74 in the pre-cohort and 121 in the post-cohort. Baseline characteristics were similar between cohorts with the most common indication for warfarin use being atrial fibrillation (48.6% versus 47.1%) and reversal being intracerebral hemorrhage (68.9% versus 43.0%). Achievement of the primary endpoint occurred in 92% versus 95% (p = 0.097) of patients. A statistically significant difference was seen between cohorts regarding median dose and cost of 4 F-PCC administered (p < 0.001). Eleven thromboembolic events occurred with three events in the pre-cohort and eight events in the post-cohort (p = 0.453). A fixed-dose of 1500IU of 4 F-PCC was effective in reversing INR to less than two in most patients regardless of reversal indication with minimal thrombotic risks., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Thromboembolic events are serious left ventricular thrombus (LVT) complications. Despite the limitations of vitamin K antagonist (VKA) drugs, it continues to be the recommended oral anticoagulation for LVT. Recently, nonvitamin K oral antagonist (NOAC) has gained popularity as an off-labeled treatment for systemic embolism prevention in LVT., Objective: In this study, we aim to compare the outcomes (stroke and bleeding) of warfarin versus NOAC therapy in patients with LVT., Methods: This retrospective cohort study compares NOAC and VKA therapy in LVT patients. We enrolled 201 patients with an echocardiography-confirmed LVT from January 2018 to December 2022. Patients who received NOAC therapy (NOAC, n = 77) were compared to VKA patients (VKA, n = 124). The primary endpoint was a composite of stroke, minor and major bleeding., Results: The median follow-up time was 17 months (25 th -75 th percentiles: 8-38). On unmatched analysis, both groups had no difference in major bleeding (log-rank, P = 0.61) and stroke (log-rank, P = 0.77). However, all bleeding events were higher with NOAC (log-rank, P = 0.01). On matched analysis, there was no difference between both groups in the overall bleeding events ( P = 0.08), major bleeding ( P = 0.57), and stroke ( P = 0.66). Minor bleeding was significantly lower in the VKA group ( P = 0.04)., Conclusion: In patients with LVT, NOAC was as effective as VKA in stroke prevention without increasing the risk of major bleeding., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Family Medicine and Primary Care.)

Background: For the majority of patients with atrial fibrillation (AF), disease management has improved in recent years. However, there are still populations underrepresented or excluded in current registries and randomized controlled trials. HERA-FIB (Heidelberg Registry of Atrial Fibrillation) was planned to assess real-world evidence for the prevalence, demographic characteristics and management of patients with the diagnosis of AF presenting consecutively to a chest pain unit., Methods and Results: HERA-FIB is a retrospective, observational, single-center study on patients with a diagnosis of AF presenting to a chest pain unit from June 2009 until March 2020. This article describes the structure, governance, outcome assessment, quality and data collection processes of the registry. Additionally, characteristics of populations of special interest are described. The study consecutively enrolled 10 222 patients presenting with AF to the chest pain unit of the University Hospital of Heidelberg. Clinical parameters and patient characteristics were assessed retrospectively. Outcome parameters included rates for all-cause death, stroke, myocardial infarction and major bleedings. We were able to investigate patient cohorts of special interest such as advanced chronic kidney disease, octogenarians, and those with acute coronary syndrome who are often underrepresented in current studies and randomized controlled trials., Conclusions: HERA-FIB is one of the largest real-world single-center retrospective registries on patients with AF, which captures the era of transition from vitamin K antagonists to non-vitamin K oral anticoagulation regimens in clinical practice and offers the possibility to investigate patient populations usually underrepresented or excluded in current available randomized controlled trials and registries., Registration: URL: https://www.clinicaltrials.gov; unique identifier: NCT05995561.

Around 10% of patients with acute coronary syndrome are treated by vitamin K antagonists or non-vitamin K antagonist oral anticoagulants for various indications. The initial management of these patients is highly complex, and new guidelines specify that, only during percutaneous coronary intervention, a bolus of unfractionated heparin is recommended in one of the following circumstances: (1) if the patient is receiving a non-vitamin K antagonist oral anticoagulant; or (2) if the international normalized ratio is<2.5 in a patient being treated with a vitamin K antagonist. In this review, we report on five key messages essential for the management of these patients. There are no randomized studies to date, and we propose two diagnostic and/or therapeutic decision algorithms. However, randomized studies are needed to validate these strategies., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Venous thromboembolism is a leading cause of morbidity and mortality in patients with active cancer who require anticoagulation treatment. Choice of anticoagulant is based on careful balancing of the risks and benefits of available classes of treatment: vitamin K antagonists, low-molecular-weight heparin (LMWH), and direct oral anticoagulants (DOACs). Results from randomized controlled trials have shown the consistent efficacy of DOACs versus LMWH in the treatment of cancer-associated venous thromboembolism (VTE). However, increased major gastrointestinal bleeding was observed for edoxaban and rivaroxaban, but not apixaban, compared with LMWH dalteparin. Most guidelines recommend DOACs for the treatment of cancer-associated VTE in patients without gastrointestinal or genitourinary cancer, and with considerations for renal impairment and drug-drug interactions. These updates represent a major paradigm shift for clinicians in the Middle East and North Africa. The decision to prescribe a DOAC for a patient with cancer is not always straightforward, particularly in challenging subgroups of patients with an increased risk of bleeding. In patients with gastrointestinal malignancies who are at high risk of major gastrointestinal bleeds, apixaban may be the preferred DOAC; however, caution should be exercised if patients have upper or unresected lower gastrointestinal tumors. In patients with gastrointestinal malignancies and upper or unresected lower gastrointestinal tumors, LMWH may be preferred. Vitamin K antagonists should be used only when DOACs and LMWH are unavailable or unsuitable. In this review, we discuss the overall evidence for DOACs in the treatment of cancer-associated VTE and provide treatment suggestions for challenging subgroups of patients with cancer associated VTE., Competing Interests: Alexander T Cohen has received contracts and consulting fees for other projects from Bristol Myers Squibb and Pfizer; payments for lectures and presentations from Bristol Myers Squibb and Pfizer; and Advisory Board fees for other projects from Bristol Myers Squibb and Pfizer, all paid to a consulting company. He also reports personal fees from AbbVie, AstraZeneca, Bayer AG, Daiichi Sankyo, and Pfizer, outside the submitted work. Mahmoud Marashi reports personal fees from Bayer, Pfizer and Sanofi during the conduct of the study; personal fees from Astra Zeneca, Janssen, Takeda, Amgen, Novartis, Roche, BMS, Novo, Sobi, Alexion, outside the submitted work. All the other authors declare no conflicts of interest in this work., (© 2024 Bazarbashi et al.)

Background: Toxicity or treatment failure related to drug-drug interactions (DDIs) are known to significantly affect morbidity and hospitalization rates. Despite the availability of numerous databases for DDIs identification and management, their information often differs. Oral anticoagulants are deemed at risk of DDIs and a leading cause of adverse drug events, most of which being preventable. Although many databases include DDIs involving anticoagulants, none are specialized in them. Aim and method: This study aims to compare the DDIs information content of four direct oral anticoagulants and two vitamin K antagonists in three major DDI databases used in Switzerland: Lexi-Interact, Pharmavista, and MediQ. It evaluates the consistency of DDIs information in terms of differences in severity rating systems, mechanism of interaction, extraction and documentation processes and transparency. Results: This study revealed 2'496 DDIs for the six anticoagulants, with discrepant risk classifications. Only 13.2% of DDIs were common to all three databases. Overall concordance in risk classification (high, moderate, and low risk) was slight (Fleiss' kappa = 0.131), while high-risk DDIs demonstrated a fair agreement (Fleiss' kappa = 0.398). The nature and the mechanism of the DDIs were more consistent across databases. Qualitative assessments highlighted differences in the documentation process and transparency, and similarities for availability of risk classification and references. Discussion: This study highlights the discrepancies between three commonly used DDI databases and the inconsistency in how terminology is standardised and incorporated when classifying these DDIs. It also highlights the need for the creation of specialised tools for anticoagulant-related interactions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Coumau, Gaspar, Terrier, Schulthess-Lisibach, Lutters, Le Pogam and Csajka.)

Purpose: The aim of this study was to investigate the risks and outcomes of patients with long-term oral anticoagulation (OAC) undergoing spine surgery., Methods: All patients on long-term OAC who underwent spine surgery between 01/2005 and 06/2015 were included. Data were prospectively collected within our in-house Spine Surgery registry and retrospectively supplemented with patient chart and administrative database information. A 1:1 propensity score-matched group of patients without OAC from the same time interval served as control. Primary outcomes were post-operative bleeding, wound complications and thromboembolic events up to 90 days post-surgery. Secondary outcomes included intraoperative blood loss, length of hospital stay, death and 3-month post-operative patient-rated outcomes., Results: In comparison with the control group, patients with OAC (n = 332) had a 3.4-fold (95%CI 1.3-9.0) higher risk for post-operative bleeding, whereas the risks for wound complications and thromboembolic events were comparable between groups. The higher bleeding risk was driven by a higher rate of extraspinal haematomas (3.3% vs. 0.6%; p = 0.001), while there was no difference in epidural haematomas and haematoma evacuations. Risk factors for adverse events among patients with OAC were mechanical heart valves, posterior neck surgery, blood loss > 1000 mL, age, female sex, BMI > 30 kg/m 2 and post-operative PTT levels. At 3-month follow-up, most patients reported favourable outcomes with no difference between groups., Conclusion: Although OAC patients have a higher risk for complications after spine surgery, the risk for major events is low and patients benefit similarly from surgery., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Limited data are available regarding the safety and effectiveness of 4-factor prothrombin complex concentrate (4F-PCC) in patients experiencing major hemorrhage or requiring expeditious surgical intervention, both globally and within Japan., Methods: We executed a prospective, observational post-marketing surveillance study of patients receiving 4F-PCC for the first time between September 19, 2017 and August 15, 2018 in Japan. Patients were subjected to a comprehensive follow-up for a duration of 4 weeks., Results: Of 1381 eligible patients, 1271 (92%) received a vitamin K antagonist. Among these, 58% were aged ≥ 75 years, 49% manifested atrial fibrillation, 17% presented with valvular heart disease, and 6% exhibited venous thromboembolism. The median (range) international normalized ratio was 2.67 (0.96-27.11) at baseline and 1.21 (0.45-6.61) at first measurement post-administration of 4F-PCC. The most common reason for 4F-PCC administration was intracranial hemorrhage (59.6%), followed by gastrointestinal bleeding (6.6%). Hemostatic effectiveness was achieved in 85.8% of patients. The incidences of adverse drug reactions (ADRs) and serious ADRs were 3.9% and 2.8%, respectively. Thromboembolic events (TEEs) occurred in 20 (1.5%) patients, with a mean onset of 10 days. The majority of TEEs were classified as nervous system disorders (55%). At the time of TEE, only 13% of patients resumed anticoagulant therapy., Conclusion: The incidence of TEEs following treatment with 4F-PCC did not surpass those observed in phase 3 trials. No novel safety signals were identified. The safety and effectiveness of 4F-PCC in Japanese real-world practice were in harmony with the observations of prior studies., (© 2024. The Author(s).)

Venous thromboembolism (VTE) is a rare and heterozygous disease in children. Management of VTE in children is complicated by age-related differences in epidemiology, recurrent VTE and bleeding risk, hemostatic proteins and pharmacokinetics of anticoagulants. Recently, the choice of anticoagulation has expanded to oral factor IIa and Xa inhibitors, which have been authorized for children for treatment of acute VTE and extended secondary prevention. These drugs have several properties that make them extremely suitable for use in children, including oral administration, antithrombin independence, less interactions with food and drugs and no need for monitoring. Unfortunately, the phase 3 studies had many exclusion criteria, and only a few term neonates and infants were included in these studies. Additional real-world data is needed to make evidence-based recommendations in these age and patient groups, as well., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: CH van Ommen reports a relationship with Bayer BV that includes: consulting or advisory. CH van Ommen reports a relationship with Boehringer Ingelheim that includes: consulting or advisory., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: There is currently no established recommendation for antithrombotic treatment following transcatheter mitral valve replacement (TMVR). However, based on the analogy with surgical mitral bioprosthesis, vitamin K antagonists (VKAs) are predominantly used., Objectives: The purpose of this study was to compare bleeding and thrombotic events associated with direct oral anticoagulants (DOACs) or VKAs in a prospective cohort of TMVR patients., Methods: We enrolled consecutive patients who underwent transseptal TMVR using a SAPIEN family prosthesis at our center between 2011 and 2023. The primary outcome was the occurrence of bleeding. VKAs were administered to patients until October 2019, after which DOACs were prescribed. The median follow-up was 4.7 months (Q1-Q3: 2.6-6.7 months)., Results: A total of 156 patients were included. The mean age was 65 ± 18.5 years, and 103 patients (66%) were women. The median EuroSCORE II was 7.48% (Q1-Q3: 3.80%-12.97%). Of the participants, 20.5% received DOACs and 79.5% were treated with VKAs. The primary outcome was observed in 50 (40%) patients in the VKA group and 3 (9%) patients in the DOAC group (adjusted HR: 0.21; 95% CI: 0.06-0.74; P = 0.02). Treatment with DOAC was associated with a shorter length of hospital stay. No significant differences were found in terms of thrombotic events, major vascular complications, stroke, or death., Conclusions: The use of DOACs after TMVR, compared with VKAs, appears to reduce the risk of bleeding complications and decrease the length of hospital stay for patients, without a significant increase in the risk of thrombotic events., Competing Interests: Funding Support and Author Disclosures Dr Himbert is a proctor for Edwards Lifesciences and Abbott. Dr Brochet is a proctor for Abbott. Prof Urena has received speaker fees from Edwards Lifesciences and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: direct oral anticoagulants (DOACs) are an alternative to conventional antagonist of vitamin-K (AVK). However, immune suppressive drugs (ISDs) may interfere with DOACs pharmacokinetic., Aim of This Study: evaluate safety and efficacy profile of DOACs compared to AVK in kidney transplant recipients (KTRs) treated with ISDs., Methods: a multi-center study from 4 Italian University hospitals enrolling consecutive KTRs on DOACs or AVK was carried out. Sixty-six patients on DOACs were compared with fifty patients on AVK with similar clinical features. Serial evaluation of renal function and serum levels of ISDs during 18 months follow-up (FU) was performed., Results: Mean age of DOACs patients was 67±9 and mean eGFR was 58,3± 30,4mL/min/1.73m 2 . ISDs included tacrolimus (n=47, 71%), cyclosporin (n=13, 20%), everolimus (n=10, 7%) and sirolimus (n=4, 6%). After 14 days of DOACs therapy initiation there was a slight increase of serum levels of tacrolimus (+0.19±0.67 p=0.80) and cyclosporine (+0.12±0.25 p=0.94) not statistically significant. Levels of Tacrolimus and cyclosporin were stable at serial evaluation during 18-months follow-up. There were no thromboembolic events among patients treated with DOACs or AVK and no differences in term of major bleeding (6% vs 4% p=0.69), at long-term follow-up. There was no difference in term of eGFR decline from start therapy to 18 months FU between DOACs vs AVK therapy (-3.9±1 vs -3.8±2 p=0.82)., Conclusion: DOACs have similar safety and efficacy than AVK among KTRs treated with ISDs. However, careful evaluation of potential drug interaction and ISDs serum levels is needed., Competing Interests: Declaration of Competing Interest The authors declare they have no conflict of interest. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Declaration of Competing Interest Dr. Shiga is a member of the speakers’ bureaus for Bristol-Myers Squibb. He also received lecture fees from Daiichi Sankyo and Bristol-Myers Squibb. He also received research funding from Daiichi Sankyo. The remaining authors have no competing interests to declare.

Objective: To evaluate the efficacy and safety of direct oral anticoagulants (DOACs) compared to warfarin in patients with inferior vena cava (IVC) thrombus., Methods: This was a single-system, retrospective cohort study of hospitalized adult patients with IVC thrombus treated with a DOAC or warfarin therapy. The primary efficacy endpoint was the thrombus resolution on imaging, and the primary safety endpoint was major bleeding, both assessed within 6 months of hospital discharge. Secondary endpoints included hospitalization for a bleeding-related event, pulmonary embolism, or death within 6 months of hospital discharge., Results: A total of 33 patients were included in the study. Twenty-three (70%) patients received a DOAC, and 10 (30%) received warfarin. Of the 10 patients with repeat imaging available, complete resolution was noted in two (33%) DOAC patients and no warfarin patients (p = .5). Major bleeding occurred in two (8.7%) DOAC patients and one (10%) warfarin patient (p = .9). No significant differences in secondary endpoints were observed between groups., Conclusions: There were no differences in efficacy and safety between patients receiving DOACs or warfarin for the treatment of IVC thrombus, although results are limited by the small patient population and number of patients with repeat imaging available., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Aims: Current clinical guidelines for treating left ventricular thrombus (LVT) are limited by inadequate evidence to inform the comparative efficacy of oral anticoagulants. In this meta-analysis, we aimed to compare the efficacy and safety of direct oral anticoagulants (DOAC) to vitamin K antagonists (VKA) in patients with LVT., Methods: Four standard databases were searched for relevant literature comparing the efficacy and safety between DOAC and VKA for LVT treatment, published before August 19, 2023. Both the randomized controlled trials and observational studies were included in the analysis. The outcomes of interest were the resolution of LVT, all-cause mortality, stroke, systemic embolism, and bleeding. Data from the selected studies were extracted and analyzed using RevMan 5.4 using odds ratio., Results: Among 3959 studies from the database search and bibliography review, 33 were included in the analysis. LVT resolution was observed in 72.59% in the DOAC group versus 67.49% in the VKA group (odds ratio [OR]: 1.28, confidence interval [CI]: 1.07-1.53). Mortality was lower in the DOAC group (11.71% vs. 18.56%) (OR: 0.60, CI: 0.36-1.00; borderline statistical significance). Likewise, bleeding events (9.60% vs. 13.19%) (OR: 0.65, CI: 0.52-0.81) and stroke (7.54% vs. 11.04%) (OR: 0.71, CI: 0.53-0.96) were also significantly lower in the DOAC group., Conclusion: DOAC use for LVT showed better thrombus resolution and reduced risk of bleeding and stroke compared to VKA. Likewise, DOAC use was associated with lower mortality with borderline statistical significance., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Objective: Although oral anticoagulant use has been implicated in worse outcomes for patients with a traumatic brain injury (TBI), prior studies have mostly examined the use of vitamin K antagonists (VKAs). In an era of increasing use of direct oral anticoagulants (DOACs) in lieu of VKAs, the authors compared the survival outcomes of TBI patients on different types of premorbid anticoagulation medications with those of patients not on anticoagulation., Methods: The authors retrospectively reviewed the records of 1186 adult patients who presented at a level I trauma center with an intracranial hemorrhage after blunt trauma between 2016 and 2022. Patient demographics; comorbidities; and pre-, peri-, and postinjury characteristics were compared based on premorbid anticoagulation use. Multivariable Cox proportional hazards regression modeling of mortality was performed to adjust for risk factors that met a significance threshold of p < 0.1 on bivariate analysis., Results: Of 1186 patients with a traumatic intracranial hemorrhage, 49 (4.1%) were taking DOACs and 53 (4.5%) used VKAs at the time of injury. Patients using oral anticoagulants were more likely to be older (p < 0.001), to have a higher Charlson Comorbidity Index (p < 0.001), and to present with a higher Glasgow Coma Scale (GCS) score (p < 0.001) and lower Injury Severity Score (ISS; p < 0.001) than those on no anticoagulation. Patients using VKAs were more likely to undergo reversal than patients using DOACs (53% vs 31%, p < 0.001). Cox proportional hazards regression demonstrated significantly increased hazard ratios (HRs) for VKA use (HR 2.204, p = 0.003) and DOAC use (HR 1.973, p = 0.007). Increasing age (HR 1.040, p < 0.001), ISS (HR 1.017, p = 0.01), and Marshall score (HR 1.186, p < 0.001) were associated with an increased risk of death. A higher GCS score on admission was associated with a decreased risk of death (HR 0.912, p < 0.001)., Conclusions: Patients with a traumatic intracranial injury who were on oral anticoagulant therapy before injury demonstrated higher mortality rates than patients who were not on oral anticoagulation after adjusting for age, comorbid conditions, and injury presentation.

Introduction: Current guidelines recommend that patients with cerebral venous thrombosis (CVT) should be treated with vitamin K antagonists (VKAs) for 3-12 months. Direct oral anticoagulants (DOACs), however, are increasingly used in clinical practice. An exploratory randomized controlled trial including 120 patients with CVT suggested that the efficacy and safety profile of dabigatran (a DOAC) is similar to VKAs for the treatment of CVT, but large-scale prospective studies from a real-world setting are lacking., Methods: DOAC-CVT is an international, prospective, observational cohort study comparing DOACs to VKAs for the prevention of recurrent venous thrombotic events after acute CVT. Patients are eligible if they are 18 years or older, have a radiologically confirmed CVT, and have started oral anticoagulant treatment (DOAC or VKA) within 30 days of CVT diagnosis. Patients with an absolute contra-indication for DOACs, such as pregnancy or severe renal insufficiency, are excluded from the study. We aim to recruit at least 500 patients within a three-year recruitment period. The primary endpoint is a composite of recurrent venous thrombosis and major bleeding at 6 months of follow-up. We will calculate an adjusted odds ratio for the primary endpoint using propensity score inverse probability treatment weighting., Discussion: DOAC-CVT will provide real-world data on the comparative efficacy and safety of DOACs versus VKAs for the treatment of CVT., Clinical Trial Registration: ClinicalTrials.gov, NCT04660747., Competing Interests: DA reports travel support from Boehringer Ingelheim, speaker fees from Bayer, and Advisory Board participation for AstraZeneca; MH reports grants from Swiss National Science Foundation, SITEM Support Funds and Swiss Heart Foundation, all outside the submitted work; TK has received educational meeting cost assistance from Boehringer Ingelheim; RL reports fees paid to his institution for consultancy by Boehringer Ingelheim, Genentech, Ischemaview, Medtronic and Medpass; SP has received research support from BMS/Pfizer, Boehringer-Ingelheim, Daiichi Sankyo, European Union, German Federal Joint Committee Innovation Fund, German Federal Ministry of Education and Research, Helena Laboratories, and Werfen as well as speakers’ honoraria/consulting fees from Alexion, AstraZeneca, Bayer, Boehringer-Ingelheim, BMS/Pfizer, Daiichi Sankyo, Portola, and Werfen (all outside of the submitted work); MA reports personal fees from AstraZeneca, Bayer, Bristol Myers Squibb, Covidien, Daiichi Sankyo, Medtronic, Novartis, Pfizer, and Amgen; TT has received personal fees from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Inventiva, and Portola Pharma; JF has received personal fees from Boehringer Ingelheim, Bayer, and Daiichi Sankyo as well as grants from Bayer; JC has received grants paid to his institution from Boehringer Ingelheim and Bayer, and payments paid to his institution for data safety monitoring board participation by Bayer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 van de Munckhof, Sánchez van Kammen, Krzywicka, Aaron, Aguiar de Sousa, Antochi, Arauz, Barboza, Conforto, Dentali, Galdames Contreras, Ji, Jood, Heldner, Hernández-Pérez, Kam, Kleinig, Kristoffersen, Leker, Lemmens, Poli, Yeşilot, Wasay, Wu, Arnold, Lucas-Neto, Middeldorp, Putaala, Tatlisumak, Ferro and Coutinho.)

Infective endocarditis (IE) carries a high risk of vascular complications (e.g., cerebral embolism, intracerebral hemorrhage, and renal infarction), which are correlated with increased early and late mortality. Although anticoagulation is the cornerstone for management of thromboembolic complications, it remains controversial and challenging in patients with IE. An appropriate anticoagulation strategy is crucial to improving outcomes and requires a good understanding of the indication, timing, and regimen of anticoagulation in the setting of IE. Observational studies have shown that anticoagulant treatment failed to reduce the risk of ischemic stroke in patents with IE, supporting that IE alone is not an indication for anticoagulation. In the absence of randomized controlled trials and high-quality meta-analyses, however, current guidelines on IE were based largely on observational data and expert opinion, providing few specific recommendations on anticoagulation. A multidisciplinary approach and patient engagement are required to determine the timing and regimen of anticoagulation in patients with IE, especially in specific situations (e.g., receiving warfarin anticoagulation at the time of IE diagnosis, cerebral embolism or ischemic stroke, intracerebral hemorrhage, or urgent surgery). Collectively, individualized strategies on anticoagulation management of IE should be based on clinical evaluation, available evidence, and patient engagement, and ultimately be developed by the multidisciplinary team., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This work was supported by the Key Projects in the National Science and Technology Pillar Program of the 13th Five-Year Plan Period [grant number 2017YFC1308300] for the design and conduct of the study, and the National Natural Science Foundation of China [grant number 81873472] for the preparation and review of the manuscript., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Major bleeding in the treatment of atrial fibrillation is closely associated with an increased risk of death and major adverse outcomes in both the short and long term, but all bleeding events are associated with a reduced quality of life. Bleeding events are also known to reduce medication adherence. In this sense, bleeding risk scores are important tools to help predict major bleeding. However, it is not clear which scoring system is superior., Aim: In this study, our aim was to compare bleeding risk scores and to examine the factors associated with bleeding in patients with major bleeding while using vitamin K antagonists., Methods: In this retrospective and single-center study, scoring, laboratory and demographic data were analyzed with SPSS 20.0 statistical program., Results: The mean age of a total of 1434 patients included in our study was 68.2 ± 11.3 years, range was 39-93 years and 769 (53.6%) of these patients were male. Of 588 patients with major bleeding, 93 (15.8%) had intracranial hemorrhage. Logistic regression analysis comparing the scoring systems among themselves revealed that the GARFIELD-AF scoring system had a predictive effect on major bleeding independent of the effect of other scoring systems (OR: 1.532, 95% CI 1.348-1.741, p < 0.001). The area under the curve (AUC) for GARFIELD-AF was 0.690 (0.662-0.718) as a result of the ROC analysis considering the best cut-off point of 3.2% calculated for 2 years. AUC 0.659 (0.630-0.687) for HAS-BLED, AUC 0.636 (0.606-0.665) for ORBIT and AUC 0.611 (0.5810.642) for ATRIA. When we compare the patient group with the control group, it can be said that intracranial hemorrhage occurred independently of INR and TTR values, unlike in the major bleeding group (p:0.129, p:0.545)., Conclusion: In patients using vitamin K antagonists for atrial fibrillation, the GARFIELD-AF risk score was found to be superior to important bleeding risk scores such as HAS-BLED, ORBIT and ATRIA in terms of predicting major bleeding. It is an important result that intracranial hemorrhages, which have a special place among major hemorrhages, were independent of INR and TTR levels. It is noteworthy that 8.2% of patients with major bleeding had a history of minor bleeding in the last year., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Atrial fibrillation (AF) patients are more susceptible to dementia, but the results about the effect of oral anticoagulants (OACs) on the risk of dementia are not consistent. We hypothesize that OAC is associated with a reduced risk of dementia with AF and that nonvitamin K antagonist oral anticoagulants (NOAC) are superior to vitamin K antagonists (VKA). Four databases were systematically searched until July 1, 2022. Two reviewers independently selected literature, evaluated quality, and extracted data. Data were examined using pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Fourteen research studies involving 910 patients were enrolled. The findings indicated that OACs were associated with a decreased risk of dementia (pooled HR: 0.68, 95% CI: 0.55-0.82, I 2  = 87.7%), and NOACs had a stronger effect than VKAs (pooled HR: 0.87, 95% CI: 0.79-0.95, I 2  = 72%), especially in participants with a CHA2DS2VASc score ≥ 2 (pooled HR: 0.85, 95% CI: 0.72-0.99). Subgroup analysis demonstrated no statistical significance among patients aged <65 years old (pooled HR: 0.83, 95% CI: 0.64-1.07), patients in "based on treatment" studies (pooled HR: 0.89, 95% CI: 0.75-1.06), or people with no stroke background (pooled HR: 0.90, 95% CI: 0.71-1.15). This analysis revealed that OACs were related to the reduction of dementia incidence in AF individuals, and NOACs were better than VKAs, remarkably in people with a CHA2DS2VASc score ≥ 2. The results should be confirmed by further prospective studies, particularly in patients in "based on treatment" studies aged <65 years old with a CHA2DS2VASc score < 2 or without a stroke background., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Background: Direct oral anticoagulants (DOACs) are associated with bleeding. Patients often stop taking DOACs due to non-major bleeding, which may lead to stroke recurrence. We aimed to determine the risk of non-major bleeding using different DOACs to prevent strokes in atrial fibrillation (AF)., Methods: A systematic search of four databases (PubMed, EMBASE, Web of Science, and Cochrane Library) was performed to identify randomized controlled trials (RCTs) reporting non-major bleeding events in patients taking DOACs or vitamin K antagonists (VKAs). In this frequency-based network meta-analysis, odds ratios and 95% confidence intervals were used for reporting. Based on the surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated., Results: Nineteen randomized controlled trials (RCTs) (involving 85,826 patients) were included. For clinically relevant non-major bleeding, the risk for bleeding was lowest for apixaban (SUCRA, 93.9), followed by that for VKAs (SUCRA, 47.7), dabigatran (SUCRA, 40.3), rivaroxaban (SUCRA, 35.9), and edoxaban (SUCRA, 32.2). The minor bleeding safety of DOACs was ranked from highest to lowest as follows: apixaban (SUCRA, 78.1), edoxaban (SUCRA, 69.4), dabigatran (SUCRA, 48.8), and VKAs (SUCRA, 3.7)., Conclusions: Based on current evidence, for stroke prevention in patients with AF, the safest DOAC is apixaban in terms of non-major bleeding. This suggests that apixaban may have a lower risk of non-major bleeding than other anticoagulants and may help provide some clinical reference for choosing a more appropriate drug for the patient., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The relative effectiveness of anticoagulation agents in patients with atrial fibrillation (AF) who survive an intracranial hemorrhage (ICH) is unknown. This study was performed to examine the comparative effectiveness of different oral anticoagulation (OAC) on clinical outcomes in this group of patients., Methods: We performed a Bayesian network meta-analysis of randomized controlled trials (RCTs) and observational studies comparing different OAC (direct oral anticoagulant [DOAC] and warfarin) for the treatment of patients with AF who sustained ICH. Outcomes included repeat ICH, thromboembolic events, and all-cause mortality. The values derived from the surface under the cumulative ranking curve were obtained to rank the treatment hierarchy., Results: We identified 12 studies (two RCTs and ten observational studies) involving 23,265 patients; 346 patients were treated with any OAC agents; 5,006 received DOAC; 5,271 received warfarin; 12,007 received antiplatelet or no therapy, and 635 did not received relevant therapy. Both DOAC and warfarin (RR, 0.58; 95% CI, 0.45-0.74; RR, 0.83; 95% CI, 0.69-0.98) were superior to antiplatelet or no therapy in preventing thromboembolic events. Moreover, DOAC also showed superiority in preventing thromboembolic events (RR, 0.70; 95% CI, 0.58-0.83), repeat ICH (RR, 0.52; 95% CI, 0.40-0.67), and all-cause mortality (RR, 0.51; 95% CI, 0.46-0.56) than warfarin., Conclusions: Our study suggests DOACs may be a reasonable alternative to anti-platelet therapy and warfarin for patients with AF who experienced ICH. However, given the available evidence is primarily observational, further validation by ongoing trials directly comparing these two classes of drugs are needed., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: Patients after heart transplantation (HTX) often require oral anticoagulants (OACs) due to atrial arrhythmias or thromboembolic events but little is known about the post-transplant use of direct oral anticoagulants (DOACs). We investigated the frequency, indications, and complications of DOACs and vitamin K antagonists (VKAs) after HTX., Methods: We screened all adult patients for the use of post-transplant OACs who underwent HTX at Heidelberg Heart Center between 2000 and 2021. Patients were stratified by type of OAC (DOAC or VKA) and by DOAC agents (apixaban, dabigatran, edoxaban, or rivaroxaban). Indications for OACs comprised atrial fibrillation, atrial flutter, pulmonary embolism, upper and lower extremity deep vein thrombosis, as well as intracardiac thrombus., Results: A total of 115 of 459 HTX recipients (25.1%) required OACs, including 60 patients with DOACs (52.2%) and 55 patients with VKAs (47.8%). Concerning DOACs, 28 patients were treated with rivaroxaban (46.7%), 27 patients with apixaban (45.0%), and 5 patients with edoxaban (8.3%). We found no significant differences between both groups concerning demographics, immunosuppressive drugs, concomitant medications, indications for OACs, ischemic stroke, thromboembolic events, or OAC-related death. Patients with DOACs after HTX had a significantly lower one-year rate of overall bleeding complications ( p = 0.002) and a significantly lower one-year rate of gastrointestinal hemorrhage ( p = 0.011) compared to patients with VKAs after HTX in the Kaplan-Meier estimator., Conclusions: DOACs were comparable to VKAs concerning the risk of ischemic stroke, thromboembolic events, or OAC-related death but were associated with significantly fewer bleeding complications in HTX recipients.

Background: The optimal anticoagulation strategy for patients with bioprosthetic valves and atrial fibrillation remains uncertain. We conducted a meta-analysis using updated evidence comparing direct anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with bioprosthetic valves and atrial fibrillation., Methods: Medline and Embase were searched through March 2021 to identify randomized controlled trials (RCTs) and observational studies investigating the outcomes of DOAC therapy and VKA therapy in patients with bioprosthetic valves and atrial fibrillation. The outcomes of interest were all-cause death, major bleeding, and stroke or systemic embolism., Results: Our analysis included 4 RCTs and 6 observational studies enrolling a total of 6405 patients with bioprosthetic valves and atrial fibrillation assigned to a DOAC group (n = 2142) or a VKA group (n = 4263). Pooled analysis demonstrated the similar rates of all-cause death (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.77-1.05; P = .18; I 2  = 0%) in the DOAC and VKA groups. However, the rate of major bleeding was significantly lower in the DOAC group (HR, 0.66; 95% CI, 0.48-0.89; P = .006; I 2  = 0%), whereas the rate of stroke or systemic embolism was similar in the 2 groups (HR, 0.72; 95% CI, 0.44-1.17; P = .18; I 2  = 39%)., Conclusions: DOAC might decrease the risk of major bleeding without increasing the risk of stroke or systemic embolism or all-cause death compared with VKA in patients with bioprosthetic valves and atrial fibrillation., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Aims: Atrial fibrillation (AF) is a risk factor for brain infarction, which can lead to epilepsy. We aimed to investigate whether treatment of AF with direct oral anticoagulants (DOACs) affects the risk of epilepsy in comparison to treatment with the vitamin K antagonist phenprocoumon (PPC)., Methods and Results: We performed an active comparator, nested case-control study based on the German Pharmacoepidemiological Research Database that includes claims data from statutory health insurance providers of about 25 million persons since 2004. In 2011-17, 227 707 AF patients initiated treatment with a DOAC or PPC, of which 1828 cases developed epilepsy on current treatment with an oral anticoagulant. They were matched to 19 084 controls without epilepsy. Patients with DOAC treatment for AF had an overall higher risk of epilepsy with an odds ratio of 1.39, 95% CI (1.24; 1.55) compared to current PPC treatment. Cases had higher baseline CHA2DS2-VASc scores and more frequently a history of stroke than controls. After excluding patients with ischaemic stroke prior to the diagnosis of epilepsy, the risk of epilepsy was still higher on DOACs than on PPC. In contrast, within a cohort of patients with venous thromboembolism, the risk of epilepsy on treatment with DOACs was less elevated [adjusted odds ratio 1.15, 95% CI (0.98; 1.34)]., Conclusion: In patients with AF initiating oral anticoagulation, treatment with a DOAC was associated with an increased risk of epilepsy compared to the vitamin K antagonist PPC. Covert brain infarction may explain the observed elevated risk of epilepsy., Competing Interests: Conflict of interest: The funder of the study, Federal Joint Committee in Germany, had no influence on the design and conduct of the study, the interpretation of the data, or the decision to publish. K.P., R.F., A.V., I.P., and T.S. are working at an independent, non-profit research institute, the Leibniz Institute for Prevention Research and Epidemiology—BIPS. Unrelated to this study, BIPS occasionally conducts studies financed by the pharmaceutical industry. Almost exclusively, these are post-authorization safety studies requested by health authorities. The design and conduct of these studies as well as the interpretation and publication are not influenced by the pharmaceutical industry. No financial relationships with any organizations that might have an interest in the submitted work in the previous three years; No other relationships or activities that could appear to have influenced the submitted work., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purpose of Review: To address the following question: Are vitamin K antagonists (VKA) obsolete as stroke prevention therapy for patients with atrial fibrillation (AF) and thromboembolic risk factors?, Recent Findings: A patient-level meta-analysis of the pivotal phase III randomized trials confirmed the favorable treatment effect of direct oral anticoagulants (DOAC) over VKA in multiple key patient subgroups. Among patients with AF and rheumatic heart disease (85% of whom had mitral stenosis), a randomized trial showed that rivaroxaban was not superior to VKA for stroke prevention. Caution should be exercised when prescribing DOAC for AF-related stroke prevention for patients with elevated body mass indices or history of bariatric surgery, patients with bioprosthetic heart valves, and those who require treatment with drugs that interact with cytochrome P450 and P-glycoprotein. Drug costs associated with DOAC remain considerably higher than VKA, by up to 30-fold. Direct oral anticoagulants are preferable over VKA in the large majority of eligible patients with AF and thromboembolic risk factors. The use of DOAC should be avoided for patients with mechanical heart valves or moderate/severe rheumatic mitral stenosis. Vitamin K antagonist is a reasonable option for patients who are under-represented in randomized trials, when there are significant drug-drug interactions or when patients cannot afford DOAC agents due to their higher costs., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The management of patients who are receiving chronic oral anticoagulation therapy and require an elective surgery or an invasive procedure is a common clinical scenario., Research Question: What is the best available evidence to support the development of American College of Chest Physicians guidelines on the perioperative management of patients who are receiving long-term vitamin K agonist (VKA) or direct oral anticoagulant (DOAC) and require elective surgery or procedures?, Study Design and Methods: A literature search including multiple databases from database inception through July 16, 2020, was performed. Meta-analyses were conducted when appropriate., Results: In patients receiving VKA (warfarin) undergoing elective noncardiac surgery, shorter (< 3 days) VKA interruption is associated with an increased risk of major bleeding. In patients who required VKA interruption, heparin bridging (mostly with low-molecular-weight heparin [LMWH]) was associated with a statistically significant increased risk of major bleed, representing a very low certainty of evidence (COE). Compared with DOAC interruption 1 to 4 days before surgery, continuing DOACs may be associated with higher risk of bleeding demonstrated in some, but not all studies. In patients who needed DOAC interruption, bridging with LMWH may be associated with a statistically significant increased risk of bleeding, representing a low COE., Interpretation: The certainty in the evidence supporting the perioperative management of anticoagulants remains limited. No high-quality evidence exists to support the practice of heparin bridging during the interruption of VKA or DOAC therapy for an elective surgery or procedure, or for the practice of interrupting VKA therapy for minor procedures, including cardiac device implantation, or continuation of a DOAC vs short-term interruption of a DOAC in the perioperative period., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Purpose: Limited real-world data are available on the survival of patients treated with vitamin K antagonists (VKAs) versus with direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (AF). In this nationwide registry, we analyzed the mortality risk of patients with nonvalvular AF taking DOACs versus VKAs, with a special attention to the early treatment period., Methods: The Hungarian National Health Insurance Fund (NHIF) database was searched to identify patients treated with VKA or DOAC as a thromboembolic prophylaxis for nonvalvular AF between 2011 and 2016. The overall and the early (0-3, 4-6, and 7-12 months) mortality risks with the 2 types of anticoagulation were compared. A total of 144,394 patients with AF treated with either a VKA (n = 129,925) or a DOAC (n = 14,469) were enrolled., Findings: A 28% improvement in 3-year survival with DOAC treatment compared with VKA treatment was shown. Mortality reduction with DOACs was consistent across different subgroups. However, younger patients (30-59 years old) initiated on DOAC therapy had the greatest RRR (53%) in mortality. Furthermore, DOAC treatment also yielded a benefit of greater magnitude (HR = 0.55; 95% CI, 0.40-0.77, P = 0.001) in the lower (0-1) CHA 2 DS 2 -VASc score segment and in those with fewer (0-1) bleeding risk factors (HR = 0.50, CI 0.34-0.73, P = 0.001). The RRR in mortality with DOACs was 33% within the first 3 months, and 6% in the second year., Implications: Thromboembolic prophylaxis with DOACs in this study yielded significantly lower mortality compared with VKA treatment in patients with nonvalvular AF. The largest benefit was shown in the early period after treatment initiation, as well as in younger patients, those with a lower CHA 2 DS 2 -VASc score, and those with fewer bleeding risk factors., Competing Interests: Declaration of Interest Dr Rokszin and Ms Fábián were employed by RxTarget Ltd. Their contribution to this study analysis was financially compensated by the Hungarian Society of Cardiology. Dr Becker reports personal fees from Novo Nordisk, Richter Gedeon Nyrt, and TEVA. Dr Aradi reports lecture fees from Bayer AG, Pfizer, Boehringer Ingelheim, and MSD Pharma. Dr Merkely reports grants or contracts from Medtronic and Boston Scientific; and personal fees from Biotronik and Abbott. Dr Járai reports support for attending meetings from Egis and Pfizer; advisory board membership at Bayer, Berlin Chemie, KRKA, Novartis, Novo Nordisk, Pfizer, Sanofi, and TEVA; and board membership at the Hungarian Society of Hypertension, Hungarian Society of Cardiology, Hungarian Society of Angiology and Vascular Surgery, and Hungarian Society of Experimental and Clinical Pharmacology. The authors have indicated that they have no other conflicts of interest regarding the content of this article., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: We aimed to determine the safety of direct oral anticoagulants (DOACs) for stroke prevention and treatment in patients with atrial fibrillation (AF)., Methods: A systematic search of four databases (PubMed, EMBASE, Web of Science, and Cochrane Library) was performed to identify randomized controlled trials (RCTs) reporting severe bleeding events in patients taking DOACs or vitamin K antagonists (VKAs). In this frequency-based network meta-analysis, odds ratios and 95% confidence intervals were used for reporting. Based on the surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated., Results: Twenty-three RCTs met the inclusion criteria, and a total of 87,616 patients were enrolled. The bleeding safety of DOACs for stroke prevention and treatment in patients with AF was ranked from highest to lowest as follows: fatal bleeding: edoxaban (SUCRA,80.2), rivaroxaban (SUCRA,68.3), apixaban (SUCRA,48.5), dabigatran (SUCRA,40.0), VKAs (SUCRA,12.9); major bleeding: dabigatran (SUCRA,74.0), apixaban (SUCRA,71.5), edoxaban (SUCRA,66.5), rivaroxaban (SUCRA,22.7), VKAs (SUCRA,15.4); gastrointestinal bleeding: apixaban (SUCRA,55.9), VKAs (SUCRA,53.7), edoxaban (SUCRA,50.5), rivaroxaban (SUCRA,50.4), dabigatran (SUCRA,39.5); intracranial hemorrhage: dabigatran (SUCRA,84.6), edoxaban (SUCRA,74.1), apixaban (SUCRA,65.8), rivaroxaban (SUCRA,24.4), VKAs (SUCRA,1.1)., Conclusion: Based on current evidence, for stroke prevention and treatment in patients with AF, the most safe DOAC is edoxaban in terms of fatal bleeding; dabigatran in terms of major bleeding and intracranial hemorrhage and apixaban in terms of gastrointestinal bleeding. However, given the nature of indirect comparisons, more high-quality evidence from head-to-head comparisons is still needed to confirm them., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: In the Dutch atrial fibrillation (AF) guideline for GPs, vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) are seen as equivalent, while in cardiology there is a preference for DOACs., Aim: To describe the pattern of oral anticoagulant (OAC) prescribing for AF by GPs and assess whether GPs proactively convert between VKAs and DOACs in patients with AF., Design & Setting: Observational study using routine practice data from 214 general practices, from 2017 until 2019., Method: Patients aged ≥60 years diagnosed with AF, who had been prescribed OACs by their GPs in 2018 were included. A distinction was made between starters, who were participants who did not use OACs in 2017, and prevalent users. It was observed and recorded whether patients switched between VKAs and DOACs., Results: A total of 12 516 patients with AF were included. Four hundred and seventy-six patients (4%) started OACs in 2018; 12 040 patients were prevalent OAC users. When GPs started patients on OACs, DOACs were prescribed the most (88%). Among prevalent users, more than half of the patients used VKAs (60%). GPs switched between OACs for 1% of starters and 0.6% of prevalent users in 2018 and 2019., Conclusion: Dutch GPs predominantly start with DOACs in newly diagnosed patients with AF. Prevalent patients predominantly use VKAs and switching from a DOAC to a VKA is unusual. Consequently, the number of patients using VKAs will decline in the upcoming years. This trend raises questions about the future of organising frequent international normalised ratio (INR) checks for VKA users., (Copyright © 2023, The Authors.)

Background: Good quality anticoagulation among patients with operated valvular heart disease is needed to reduce ischaemic and thromboembolic complications. There is limited evidence regarding factors that affect anticoagulation control in patients implanted with mechanical or tissue prosthetic valve(s)., Aim: To examine the quality of and factors that affect anticoagulation control, major adverse clinical events and all-cause death in operated valvular heart disease patients with and without atrial fibrillation who are receiving a vitamin K antagonist., Methods: Quality of anticoagulation were retrospectively assessed among 456 operated valvular heart disease patients [164 (36%) with AF and 290 (64%) without AF] via time in therapeutic range (TTR) (Rosendaal method) and percentage of INRs in range (PINRR) over a median of 6.2 (3.3-8.5) years. VHD was defined by the presence of a mechanical or tissue prosthetic valve at the mitral, aortic, or both sites., Results: Mean age 51 (14.7), 64.5% men. Most (96.1%) had a mechanical prosthesis and 64% had aortic valve replacement. Overall, mean TTR was 58.5% (14.6) and PINRR was 50.1% (13.8). Operated valvular heart disease patients with AF had significantly lower mean TTR and PINRR (TTR: 55.7% (14.2) vs. 60.1% (14.6); p = 0.002, respectively, PINRR: 47.4% (13.5) vs. 51.6% (13.7); p = 0.002, respectively), and a lower proportion of TTR ≥ 70%, despite a similar number of INR tests compared to those without AF. Predictors of TTR < 70% were female sex, AF and anaemia/bleeding history. Significantly higher proportions of operated valvular heart disease patients with AF died (20.7% vs. 5.8%; p < 0.001), but ≥1 MACE rates were similar between the two groups., Conclusions: Operated valvular heart disease patients with AF at baseline have poorer anticoagulation control compared to those without AF. The presence of concomitant AF, anaemia/bleeding history and female sex independently predicted poor TTR. Stringent INR monitoring is needed to improve anticoagulation control and prevent major adverse clinical events in patients with operated valvular heart disease.

Background: Previous evidence indicated that atrial fibrillation (AF) patients with polypharmacy presented increased probability of adverse events. We investigated the prevalence of polypharmacy, risk factors for polypharmacy, and the impact of polypharmacy in clinical outcomes in a 'real-world' cohort of AF patients starting vitamin K antagonists (VKAs)., Methods: Prospective study including AF outpatients starting VKA therapy from July, 2016 to June, 2018. At inclusion, all concomitant drugs were carefully collected and recorded. Polypharmacy was defined as the intake of ≥ 5 concomitant drugs. During 2-years of follow-up, ischemic strokes/transient ischemic attacks (TIAs), fatal/nonfatal myocardial infarctions (MIs), bleeding events, venous thromboembolisms, and all-cause deaths were recorded., Results: 1050 patients (51.5 % females, median age 77 [69-83] years) were included, and the prevalence of polypharmacy was 32.9 % (345). Female sex (OR 1.5; 95 % CI 1.11-2.03), hypertension (OR 2.53; 95 % CI 1.51-4.22), diabetes (OR 3.11; 95 % CI 2.31-4.17), vascular disease (OR 3.08; 95 % CI 2.19-4.33), heart failure (OR 1.86; 95 % CI 1.35-2.58) and dyslipidemia (OR 2.61; 95 % CI 1.9-3.58) were independently associated to the polypharmacy. Patients with polypharmacy showed significantly higher incidence of major bleeding, net clinical outcomes (composite of major bleeding, ischemic stroke/TIA, and mortality), MACE (composite of ischemic stroke/TIA, MI, and cardiovascular death), and composite thrombotic/thromboembolic events; being an independent risk factor for major bleeding (HR 1.77, 95 % CI 1.07-2.92), and composite thrombotic/thromboembolic events (HR 1.55, 95 % CI 1.05-2.31)., Conclusion: In this "real world" AF cohort, polypharmacy was highly prevalent and conditioned worse prognosis due to its association with bleeding and thromboembolic events., Competing Interests: Conflicts of interest statement JMRC: Consultant for Idorsia Pharmaceuticals LTD. SA: Consultant and speaker for Bayer, Boehringer Ingelheim and Daiichi-Sankyo. GYHL: Consultant and speaker for BMS/Pfizer, Boehringer Ingelheim and Daiichi-Sankyo. No fees are received personally. There is nothing to disclose for other authors., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background and objectives : Venous thromboembolism (VTE) represents a health and economic burden with consequent healthcare resource utilization. Direct oral anticoagulants (DOACs) have emerged as the mainstay option for VTE treatment but few data exist on their cost-effectiveness as compared to the standard therapy (vitamin K antagonists (VKAs)). This study aimed to assess the cost-effectiveness of rivaroxaban compared to VKAs in VTE treatment by calculating the incremental cost effectiveness ratio (ICER). Materials and methods : We conducted a prospective observational study based on the REMOTEV registry, including patients hospitalized for VTE from 23 October 2013 to 31 July 2015, to evaluate the impact of the anticoagulant treatment (DOACs versus VKAs) on 6-month complications: major or clinically relevant non-major bleeding, VTE recurrence and all-cause death. Rivaroxaban was the only DOAC prescribed in this study. The ICER was calculated as the difference in costs divided by the difference in effectiveness. Results : Among the 373 patients included, 279 were treated with rivaroxaban (63.1 ± 17.9 years old; 49% men) and 94 with VKAs (71.3 ± 16.6 years old; 46% men). The mean cost was EUR 5662 [95% CI 6606; 9060] for rivaroxaban and EUR 7721 [95% CI 5130; 6304] for VKAs, while effectiveness was 0.0586 95% CI [0.0114; 0.126] for DOACs and 0.0638 [95% CI 0.0208; 0.109] for VKAs. The rivaroxaban treatment strategy was dominant with costs per patient EUR 2059 lower [95% CI -3582; -817] and a higher effectiveness of 0.00527 [95% CI -0.0606; 0.0761] compared to VKAs. Conclusions : This study provides real-world evidence that rivaroxaban is not only an efficient and safe alternative to VKAs for eligible VTE patients, but also cost-saving.

Background: Edoxaban is a novel oral anticoagulant which may decrease the risk of stroke and systemic embolism in patients suffering from atrial fibrillation (AF). However, the decreased efficacy of edoxaban versus warfarin for the avoidance of stroke and systemic embolism in AF with creatinine clearance (CrCl) > 95 mL/min has been reported. The purpose of this meta-analysis is to further clarify the safety (major bleeding) and efficacy (stroke or systemic embolism) of edoxaban for AF patients with various CrCl. Methods: A systematic search of studies on edoxaban and warfarin in AF patients related to renal function was conducted in PubMed, Medline, Web of Science databases, EBSCO, Embase, and the Cochrane Central Register of Controlled Trials. In this meta-analysis (protocol number: PROSPERO CRD 42021245512), we included studies that provide specific data on three outcomes: ischemic stroke or systemic embolism (S/SE), bleeding, and all-cause mortality. Results: This meta-analysis enrolled two randomized controlled trials (RCTs) studies and two retrospective studies that enrolled 28,065 patients. According to CrCl, subjects are divided into three groups (CrCl 30−50 mL/min, CrCl 50−95 mL/min, CrCl > 95 mL/min). In AF patients with CrCl 30−50 mL/min, edoxaban 30 mg daily is similar to warfarin in the prevention of ischemic S/SE and all-cause mortality, resulting in lower bleeding rate and better net clinical outcome (ischemic S/SE: hazard ratio (HR), 0.85, 95% confidence interval (CI), 0.19−1.87; all-cause mortality: HR, 0.65, 95% CI, 0.35−1.19; bleeding: HR, 0.75, 95% CI, 0.60−0.93; net clinical outcome: HR, 0.75, 95% CI, 0.63−0.90). In the group of CrCl 50−95 mL/min, the net clinical outcome was more favorable with edoxaban 60 mg daily than warfarin (HR, 0.81, 95% CI: 0.68−0.96), and there was no significant difference between edoxaban 60 mg daily and warfarin in terms of prevention of bleeding, ischemic S/SE, and all-cause mortality. For AF patients with CrCl > 95 mL/min, there was a statistically significant difference in lower bleeding rate between edoxaban 60 mg daily and warfarin (bleeding: HR: 0.70, 95% CI: 0.58−0.84). There was no differential safety in ischemic S/SE, all-cause mortality, and net clinical outcome. Conclusion: Overall, edoxaban was superior to warfarin in terms of net clinical outcome in various groups of CrCl with AF patients. Although there was no significant difference in net clinical outcome between edoxaban and warfarin for AF patients with CrCl > 95 mL/min, edoxaban is not inferior to warfarin in safety and effectiveness in the various levels of CrCl. Edoxaban may be a more effective and safe treatment than warfarin for patients with chronic kidney disease (CKD) who require anticoagulation. More high-quality and long-term clinical research are needed to further estimate the effects of edoxaban.

Purpose: Cervical artery dissection (CAD) represents a unique clinical entity with a high risk of ischemic stroke. Vitamin K antagonists (VKA) showed good efficacy in CAD management but are cumbersome to use with potentially higher bleeding rates. Novel oral anticoagulants (NOAC) are easier to use and may have similar effects but lower hemorrhagic risk. In this systematic review, we compare the efficacy of NOAC to VKA as a potential alternative treatment., Methods: The literature was searched on Pubmed, PMC, and Embase via API through the Nested Knowledge AutoLit software in February 2022 for studies evaluating both NOAC and VKA. Baseline characteristics, clinical and radiographic outcomes, and hemorrhagic and ischemic complications were collected for single and double-arm studies and analyzed using random-effect subgroup meta-analysis., Findings: Overall, 11 studies were included with 699 patients treated with VKA and 53 treated with NOAC (from three studies; two were head-to-head comparative studies). There was no statistical difference in the baseline characteristics of VKA and NOAC patients. The rates of TIA/stroke in VKA and NOAC groups were 12.3% (95% CI; 0%, 28.6%) and 5.7% (95% CI; 0%, 12.2%), respectively. Major bleeding or intracranial bleeding were comparable between groups. Lesions treated with VKA showed angiographic recanalization with a rate of 51.4% (95% CI; 35.6%, 67.1%) and for those treated with NOAC was 58.4% (95% CI; 23.9%, 93.9%). The rates of good clinical outcomes were 79.9% (95% CI; 67.6%, 92.2%) in the VKA group and 91.4% (95% CI; 78.1%, 100%) in NOAC. No statistical difference was noted among any of the outcomes between the two treatment groups., Discussion and Conclusion: We highlighted comparable efficacy and safety of NOAC to VKA for stroke prevention in CAD. Further head-to-head studies are warranted to validate these results., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© European Stroke Organisation 2022.)