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Background: Direct oral anticoagulants (DOACs) are preferred for stroke prevention in nonvalvular atrial fibrillation (NVAF); however, warfarin is still used. This study examined why physicians may choose warfarin over DOACs and the associated safety outcomes in patients with NVAF. Methods: We conducted a new‐user, active‐comparator cohort study in newly diagnosed patients with NVAF to assess safety outcomes after the introduction of DOACs in Japan. Results: The median observation period was 1120 days; 1428 patients started anticoagulation therapy with warfarin and 1551 with DOACs. Warfarin was chosen for patients with lower creatinine clearance and left ventricular ejection fractions and those using aspirin and verapamil. The unadjusted risk of major bleeding was considerably higher in the warfarin group but was nonsignificant after adjusting for variables associated with the choice of warfarin, in addition to age and sex. The risk of death was higher in the warfarin group, even after adjustments for relevant variables. However, high‐risk subgroups, including those with older ages and multiple comorbidities, such as renal impairment, for whom warfarin was more likely to be selected, had severely compromised prognoses with either anticoagulant. The risk of stroke/systemic embolism was not significantly different between the two groups. Conclusions: Warfarin is often chosen for older patients with multiple comorbidities characterized by reduced renal function, which is associated with a higher risk of major bleeding and mortality. These high‐risk patients seem to have a poor prognosis regardless of the type of anticoagulant used. Thus, safe anticoagulant therapy remains a challenge for such patients. [ABSTRACT FROM AUTHOR]

Direct oral anticoagulants (DOACs) reduce stroke risk in patients with device-detected atrial fibrillation (DD-AFib) but increase major bleeding risk. The time to benefit (TTB) and time to harm (TTH) are not well quantified. The purpose of this study was to determine TTB and TTH in DOAC-treated patients with DD-AFib. Studies were identified from PubMed searching until November 2023. The primary efficacy outcome was the time to the first stroke event, and the primary safety outcome was the time to the first major bleeding event. Pooled hazard ratio (HR) and its confidence interval (CI) were calculated through reconstructed patient-level data and study-level data. Weibull model and Markov chain Monte Carlo simulation were applied to determine time to specific absolute risk change thresholds. Two trials involving DOACs—NOAH-AFNET 6 (Non–vitamin K antagonist Oral anticoagulants in patients with Atrial High rate episodes) and ARTESiA (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation)—were identified, which randomized 6548 adults with a mean age of >75 years and a median atrial high-rate episode duration ranging from 1.5 to 2.8 hours. DOACs decreased the risk of stroke (HR 0.67; 95% CI 0.50–0.90) but increased the risk of major bleeding (HR 1.57; 95% CI 1.21–2.04). A TTB of 2.67 years was needed to prevent 1 stroke per 100 DOAC-treated patients, while a TTH of 1.67 years was needed to observe 1 major bleeding. In elderly patients with low durations of DD-AFib, DOACs result in a delayed and restricted stroke-preventive benefit while posing an early-onset bleeding risk. Our findings offer new insights into the risk-benefit profile and provide clinicians an additional dimension to facilitate shared decision-making discussions with patients. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract Background Direct oral anticoagulants (DOACs) are preferred for stroke prevention in nonvalvular atrial fibrillation (NVAF); however, warfarin is still used. This study examined why physicians may choose warfarin over DOACs and the associated safety outcomes in patients with NVAF. Methods We conducted a new‐user, active‐comparator cohort study in newly diagnosed patients with NVAF to assess safety outcomes after the introduction of DOACs in Japan. Results The median observation period was 1120 days; 1428 patients started anticoagulation therapy with warfarin and 1551 with DOACs. Warfarin was chosen for patients with lower creatinine clearance and left ventricular ejection fractions and those using aspirin and verapamil. The unadjusted risk of major bleeding was considerably higher in the warfarin group but was nonsignificant after adjusting for variables associated with the choice of warfarin, in addition to age and sex. The risk of death was higher in the warfarin group, even after adjustments for relevant variables. However, high‐risk subgroups, including those with older ages and multiple comorbidities, such as renal impairment, for whom warfarin was more likely to be selected, had severely compromised prognoses with either anticoagulant. The risk of stroke/systemic embolism was not significantly different between the two groups. Conclusions Warfarin is often chosen for older patients with multiple comorbidities characterized by reduced renal function, which is associated with a higher risk of major bleeding and mortality. These high‐risk patients seem to have a poor prognosis regardless of the type of anticoagulant used. Thus, safe anticoagulant therapy remains a challenge for such patients.

Abstract Introduction Direct oral anticoagulants (DOACs) become the recommended treatment over vitamin K antagonists (VKA) in patients with non‐valvular atrial fibrillation (AF). However, their effectiveness in reducing cognitive impairment and dementia compared to VKA remains unclear. Methods A systematic literature search was conducted on Ovid MEDLINE, EMBASE, and Cochrane Database. Randomized controlled trials, cohort, or case–control study that assessed incident dementia between AF patients who received DOAC compared to VKA were selected. Relevant study characteristics and the number of incident dementia diagnosis or hazard ratios (HRs) for incident dementia and each dementia subtypes were extracted. Random‐effects model was used to perform meta‐analysis. Standardized mean differences (SMDs) were used to estimate effect sizes for continuous data. Results Twelve cohort studies comprising 1 451 069 individuals were included. The incidence of dementia was lower in AF patients prescribed DOACs compared to VKA (HR 0.88, 95% CI 0.83–0.93, I 2 = 61.2%). A lower incident dementia in DOACs group relative to VKA was significantly observed in those less than 75 years of age (

Background/Objectives: The practice of holding anticoagulation is a relatively common approach, with the aim of either preventing excessive bleeding in preparation for surgical procedures or managing acute bleeding episodes. Methods: To assess the relationship between the discontinuation of direct oral anticoagulants (DOACs) therapy and the condition of hypercoagulability, a systematic review of the literature was conducted, following PRISMA guidelines, in PubMed/MEDLINE, Cochrane, and Google Scholar. These databases were searched for all publications that described a rebound phenomenon or hypercoagulability state after DOACs discontinuation. Results: A total of 1494 articles were selected from searched databases, and 29 were eligible. A final total of 16 case reports and 14 original research articles were subjected to analysis. Conclusions: The results of this study indicate that the cessation of DOAC therapy may be associated with an increased risk of thrombotic events. More studies are required to ascertain whether DOACs treatment cessation can be linked to rebound phenomena associated with thromboembolic events. This will provide the data needed to determine the incidence and risk of this phenomenon. [ABSTRACT FROM AUTHOR]

Objective: This study assessed the pharmacokinetic (PK) interactions between clarithromycin (a P-glycoprotein [P-gp] inhibitor) and four direct oral anticoagulants (DOACs) (P-gp substrates) using physiologically based PK (PBPK) models to elucidate the influence of P-gp in the interaction between them. Methods: PBPK models for clarithromycin, DABE–dabigatran (DAB), rivaroxaban, apixaban, and edoxaban were constructed using GastroPlus™ (version 9.9), based on physicochemical data and PK parameters from the literature. The models were optimized and validated in healthy subjects. We evaluated the predictive performance of the established model and further assessed the impact of P-gp on the PK of the four DOACs. Successfully validated models were then used to evaluate potential drug–drug interactions (DDIs) between clarithromycin and the DOACs. Results: The established PBPK models accurately described the PK of clarithromycin, DABE–DAB, rivaroxaban, apixaban, and edoxaban. The predicted PK parameters (Cmax, Tmax, AUC0-t) were within 0.5–2 times the observed values. A sensitivity analysis of P-gp parameters indicated that an increase in P-gp expression was reduced by in vivo exposure to DOACs. The models demonstrated good predictive ability for DDIs between clarithromycin and the anticoagulants, and the ratio of the predicted values to the observed values of Cmax and the area under the curve (AUC) in the DDI state was within the range of 0.5–2. Conclusions: Comprehensive PBPK models for clarithromycin, DABE–DAB, rivaroxaban, apixaban, and edoxaban were developed, which can effectively predict DDIs mediated by P-gp's function. These models provide theoretical support for clinical dose adjustments and serve as a foundation for future PBPK model development for DOACs under specific pathological conditions. [ABSTRACT FROM AUTHOR]

Background/Aim: The COVID-19 pandemic has intensified inquiries into the interplay between diabetes and disease severity, and the long-term impact of long-COVID. This study specifically explored the implications of different antithrombotic treatments on COVID-19 patients. It aimed to assess the long-term efficacy and safety of Vitamin K antagonists (VKA) and direct oral anticoagulants (DOACs) in mitigating thromboembolic complications in COVID-19 patients. Patients and Methods: We conducted a study on 157 patients diagnosed with COVID-19 from August 2021 to August 2023. The study evaluated shifts in anticoagulant therapy recommendations, tracking the transition from VKA to DOACs, and analyzed associated health outcomes. Results: A significant shift from VKA to DOACs prescriptions was observed, especially in high-risk patients. Despite the change in antithrombotic treatments, incidences of varices and varices with hemorrhoids increased by 2.6% and 3.2%, respectively. Long-COVID was also linked to higher occurrences of diabetes and gastrointestinal diseases. Joint diseases rose by 14%, indicating persistent inflammation. Cardiomyopathies increased by 3.9%, predominantly in high-risk groups, and psychoanxiety disorders surged by 39.5%, highlighting the need for further research. DOAC usage was more common in older age groups, with a 10.2% increase in recommendations among high-risk patients (p<0.05). Conclusion: The study underscores the evolving landscape of antithrombotic therapy in managing COVID-19 complications. Despite the increased use of DOACs, the rise in various health conditions suggests the necessity for personalized treatment strategies tailored to patient risk profiles. [ABSTRACT FROM AUTHOR]

Introduction: Direct oral anticoagulants (DOACs) become the recommended treatment over vitamin K antagonists (VKA) in patients with non‐valvular atrial fibrillation (AF). However, their effectiveness in reducing cognitive impairment and dementia compared to VKA remains unclear. Methods: A systematic literature search was conducted on Ovid MEDLINE, EMBASE, and Cochrane Database. Randomized controlled trials, cohort, or case–control study that assessed incident dementia between AF patients who received DOAC compared to VKA were selected. Relevant study characteristics and the number of incident dementia diagnosis or hazard ratios (HRs) for incident dementia and each dementia subtypes were extracted. Random‐effects model was used to perform meta‐analysis. Standardized mean differences (SMDs) were used to estimate effect sizes for continuous data. Results: Twelve cohort studies comprising 1 451 069 individuals were included. The incidence of dementia was lower in AF patients prescribed DOACs compared to VKA (HR 0.88, 95% CI 0.83–0.93, I2 = 61.2%). A lower incident dementia in DOACs group relative to VKA was significantly observed in those less than 75 years of age (< 65 years, HR 0.83 (95% CI 0.72–0.97, I2 = 0%); 65–74 years, HR 0.86 (95% CI 0.81–0.92, I2 = 55.4%); and ≥ 75 years, HR 1.07 (95% CI 0.74–1.55, I2 = 92.5%)) and for the subgroup of patients with vascular dementia (HR 0.91, 95% CI 0.824–0.997, I2 = 0%). Conclusions: This meta‐analysis reveals a reduction in incidence of dementia in AF patients prescribed DOACs compared to VKA, particularly in those less than 75 years old and in the vascular dementia subtype. [ABSTRACT FROM AUTHOR]

(1) Background: Lower gastrointestinal bleeding (LGIB) accounts for 20% of all gastrointestinal bleeds. LGBI originates in the colon, rectum, and anus, mainly in patients who are receiving antiaggregant or anticoagulant treatment. The major causes are diverticular disease, colitis, hemorrhoids, and angiodysplasia. The literature studies underline that Direct Oral Anticoagulants (DOACs) are effective in reducing the risk of thromboembolic events but are associated with a higher risk of lower gastrointestinal bleeding (LGIB), particularly lower hemorrhoid bleeding. (2) Methods: The aim of our review is to revise the risk of hemorrhoid bleeding, pathophysiology, and management in patients taking DOACs in light of the most modern evidence. (3) Conclusions: central to the management of hemorrhoid bleeding in patients receiving DOAC therapy is the consideration of a tailored approach that respects the delicate equilibrium between the need for thromboembolic prophylaxis and the potential for bleeding complications. Cessation of anticoagulation, if clinically feasible, constitutes a fundamental cornerstone in the control of hemorrhage. This pause in therapy aims to mitigate the exacerbation of bleeding risk while offering a window for the implementation of local measures to manage hemorrhoid bleeding. [ABSTRACT FROM AUTHOR]

Bas JW van de Steeg,1 Anne C Esselink,2 Hugo AJM de Wit,1 Cornelis Kramers,1 Bart JF van den Bemt3 1Department of Clinical Pharmacy, Canisius Wilhelmina Hospital, Nijmegen, the Netherlands; 2Department of Internal Medicine, Canisius Wilhelmina Hospital, Nijmegen, the Netherlands; 3Department of Pharmacy, Sint Maartenskliniek, Nijmegen, the NetherlandsCorrespondence: Bas JW van de Steeg, Department of Clinical Pharmacy A16, Canisius Wilhelmina Hospital, Nijmegen, 6532 SZ, the Netherlands, Email b.vandesteeg@cwz.nlPurpose: Arterial and venous thromboembolism are a leading cause of mortality. Direct oral anticoagulants (DOACs) are highly effective in both stroke prevention and prevention of venous thrombotic events. Medication adherence is a prerequisite for optimal protection against thromboembolic complications. Recent studies have shown that good adherence cannot be taken for granted by DOACs. In this cross-sectional study adherence among DOAC users was investigated and associations between beliefs about medication, perceived side effects and adherence were explored.Patients and Methods: We included 100 randomly selected adult DOAC users visiting one of the two participating Dutch community pharmacies in the summer of 2020. The self-reported adherence (primary outcome) was assessed with the Medication Adherence Rating Scale-5 (MARS-5) using three different cut-off scores. Beliefs about DOACs were assessed with the Beliefs about Medicine Questionnaire Specific (BMQ-S), while side effects and side effect burden were assessed with a self-developed questionnaire based on the Lareb Intensive Monitoring (LIM) system.Results: Of the participants, 9% reported non-adherence on the primary MARS-5 cut-off score < 24. For the MARS-5 scores < 23 and < 25 non-adherence percentages of, respectively, 3 and 33% were calculated. Associations were found between adherence and both side effects and side effect burden, regardless of the MARS-5 cut-off score. Bruising and minor bleeds were the most reported side effects (both 20%). For all patients, the necessity beliefs outweighed the concern beliefs. No associations were found between adherence and either gender, indication, DOAC or dosage.Conclusion: This study confirms that adherence in patients on DOACs cannot be taken for granted. High necessity beliefs do not guarantee good adherence, as side effects impair adherence even in patients having high necessity beliefs. Therefore, we recommend that both physicians and pharmacists evaluate both adherence and side effects with these patients on a regular base.Plain Language Summary: The issueThrombosis affects many people. Complications like stroke and lung embolism are a major cause of health damage, disability and even death. Direct oral anticoagulants (DOACs) are highly effective drugs at preventing these complications. However, patients need to take their medication properly to get the best protection. Recent studies showed that not all patients consistently take their DOACs.What’s new?In this study, we discovered that patients experiencing bothersome side effect were less likely to stick to their medication schedule. The most common side effects reported were bruising and minor bleeding, by 20% each. There were no differences in how well patients took their medication based on gender, medical condition, type of DOAC or prescribed dosage. Most patients believed their medication was necessary for their health.Why is this important?This study shows that side effects hinder patients taking their medication correctly even when they believe their medication is necessary for their health. This means that patients on DOAC therapy who experience side effects may be less protected against stroke and lung embolism. Therefore, we recommend that doctors and pharmacists regularly check in with patients about any side effects they experience and how consistently they take their DOACs.What’s next?This study highlights the importance of developing, testing, and implementing practical tools to find and help patients who do not take their DOACs correctly, to ensure they are better protected against blood clots.Keywords: DOACs, compliance, MARS-5, beliefs, BMQ-S

(1) Background: Lower gastrointestinal bleeding (LGIB) accounts for 20% of all gastrointestinal bleeds. LGBI originates in the colon, rectum, and anus, mainly in patients who are receiving antiaggregant or anticoagulant treatment. The major causes are diverticular disease, colitis, hemorrhoids, and angiodysplasia. The literature studies underline that Direct Oral Anticoagulants (DOACs) are effective in reducing the risk of thromboembolic events but are associated with a higher risk of lower gastrointestinal bleeding (LGIB), particularly lower hemorrhoid bleeding. (2) Methods: The aim of our review is to revise the risk of hemorrhoid bleeding, pathophysiology, and management in patients taking DOACs in light of the most modern evidence. (3) Conclusions: central to the management of hemorrhoid bleeding in patients receiving DOAC therapy is the consideration of a tailored approach that respects the delicate equilibrium between the need for thromboembolic prophylaxis and the potential for bleeding complications. Cessation of anticoagulation, if clinically feasible, constitutes a fundamental cornerstone in the control of hemorrhage. This pause in therapy aims to mitigate the exacerbation of bleeding risk while offering a window for the implementation of local measures to manage hemorrhoid bleeding.

Apixaban, a direct oral anticoagulant drug (DOAC), typically does not require routine therapeutic drug monitoring (TDM), yet recent guidelines propose its use in specific clinical scenarios. While various antifactor Xa (anti‐FXa) chromogenic assays serve as useful proxies for measuring plasma exposure to apixaban in emergencies, they lack specificity compared with chromatographic methods. This research project is intended to the development and validation of a standardized protocol of liquid chromatography–tandem mass spectrometry (LC–MS/MS) in conformity with the ICH guidelines M10 for the measurement of apixaban in both plasma and dried plasma spots (DPSs). Samples preparation included protein precipitation after the addition of a deuterated internal standard (IS), and the chromatographic separation was carried out on a Thermo Scientific™ Accucore™ Polar Premium column (50 mm × 2.1 mm, i.d. 2.6 m). The newly developed LC–MS/MS method for apixaban mesurement from both plasma and DPS resulted linear over a wide concentration range (31.25–500 ng/mL), accurate, and reproducible without matrix effects, allowing for specific and rapid quantification. Stability was assessed on quality controls and a real sample, allowing the setting up of a robust TDM protocol that was applied to five anonymized plasma samples obtained from adult patients undergoing apixaban treatment at steady‐state. In conclusion our novel LC–MS/MS method is adequate for accurate apixaban quantitation from both plasma and DPS matrixes, and may thus facilitate the guidelines suggested implementation of apixaban TDM, even in peripheral hospitals through shipment of DPS at reference laboratories. [ABSTRACT FROM AUTHOR]

• In a cohort of elderly hospitalized patients suffering from Non-valvular Atrial Fibrillation on therapy with DOACs, women and men differed in the CHA2DS2VASc score: 5.3 ± 1.3 vs 4.2 ± 1.4 points (p < 0.0001) and in the HAS-BLED score: 2.5 ± 0.7 vs 2.3 ± 0.8 points (p = 0.009), which was significantly higher in women. • In this population Cognitive Impairment (CoI) and functional disabilities are widely represented. • Female sex increases the risk of being affected by CoI by approximately 3-fold, while improving functional limitations reduces this risk by approximately 15 %. • Furthermore, CoI and depressive symptoms increase the risk of functional impairment by approximately 2-fold and 28 %, respectively, while antihypertensive and antidiabetic therapy reduce this risk by 54 % and 43 %, respectively. Atrial fibrillation (AF) represents the most common supraventricular arrhythmia, with a prevalence of 1–3 % in the world population. Growing evidences show that AF plays an important role as a risk factor for the development of cognitive impairment (CoI) and dementia, depression and functional limitation. The purpose of the study is to evaluate, in a large cohort of elderly hospitalized patients with nonvalvular AF (NVAF) on direct oral anticoagulants (DOACs) therapy, the prevalence of CoI, depression, and functional limitation, and to assess the different variables that may be detrimental or protective on the risk of CoI or functional limitation. 1004 elderly patients were enrolled, 384 men and 620 women, with a mean age of 84±7.1 years. The two groups were comparable for the main study variables, except for age, prevalence of hypertension and CKD, which were higher in women, while ischemic heart disease was higher in men. In addition, the two groups differed in the CHA 2 DS 2 VASc score 5.3 ± 1.3 vs 4.2 ± 1.4 pts (p < 0.0001) and HAS-BLED score 2.5 ± 0.7 vs 2.3 ± 0.8 pts (p = 0.009) that were significantly higher in women. Our study revealed that in a cohort of elderly patients hospitalized with AF taking DOACs, CoI and disability are widely represented, and female sex increases the risk of being affected by CoI by about 3-fold, while improvement of functional limitations reduce this risk by about 15 %. In addition, CoI and depressive symptoms increase the risk of functional impairment about 2-fold and 28 % respectively, while antihypertensive and anti-diabetic therapy reduce this risk. [ABSTRACT FROM AUTHOR]

Background: There is currently a lack of evidence for the comparative effectiveness of Andexanet alpha and four-factor prothrombin complex concentrate (4F-PCC) in anticoagulation reversal of direct oral anticoagulants (DOACs). The primary aim of our systematic review was to verify which drug is more effective in reducing short-term all-cause mortality. The secondary aim was to determine which of the two reverting strategies is less affected by thromboembolic events. Methods: A systematic review and meta-analysis was performed. Results: Twenty-two studies were analysed in the systematic review and quantitative synthesis. In all-cause short-term mortality, Andexanet alpha showed a risk ratio (RR) of 0.71(95% CI 0.37–1.34) in RCTs and PSMs, compared to 4F-PCC (I2 = 81%). Considering the retrospective studies, the pooled RR resulted in 0.84 (95% CI 0.69–1.01) for the common effects model and 0.82 (95% CI 0.63–1.07) for the random effects model (I2 = 34.2%). Regarding the incidence of thromboembolic events, for RCTs and PSMs, the common and the random effects model exhibited a RR of 1.74 (95% CI 1.09–2.77), and 1.71 (95% CI 1.01–2.89), respectively, for Andexanet alpha compared to 4F-PCC (I2 = 0%). Considering the retrospective studies, the pooled RR resulted in 1.21 (95% CI 0.87–1.69) for the common effects model and 1.18 (95% CI 0.86–1.62) for the random effects model (I2 = 0%). Conclusion: Considering a large group of both retrospective and controlled studies, Andexanet alpha did not show a statistically significant advantage over 4F-PCC in terms of mortality. In the analysis of the controlled studies alone, Andexanet alpha is associated with an increased risk of thromboembolic events. Clinical trial registration: PROSPERO: International prospective register of systematic reviews, 2024, CRD42024548768. [ABSTRACT FROM AUTHOR]

Introduction: Venous thromboembolisms (VTEs), including deep vein thrombosis (DVT) and pulmonary embolisms (PE), are common after total knee (TKA) and hip arthroplasty (THA). Recent studies suggest that aspirin effectively prevents VTE following major orthopaedic surgery. This meta‐analysis compares randomised controlled trials (RCTs) evaluating aspirin versus direct oral anticoagulants (DOACs) for VTE prevention after primary THA and TKA. Methods: We included RCTs from 2017 to 2023 that looked at aspirin versus DOACs for VTE prophylaxis in primary THA and TKA. A search strategy was conducted which used Boolean operators and MESH terms. Primary outcomes included VTE rates, symptomatic, asymptomatic DVT and PE. Secondary outcomes were mortality and bleeding complications. Statistical analysis was performed using REVMAN software. An odds ratio with a 95% confidence interval was generated for the pooled studies. Heterogeneity was assessed using the I2 variable, and publication bias was evaluated with a funnel plot. Results: Seven RCTs with 3967 patients were included for analysis. Rivaroxaban 10 mg OD was compared to varying doses of aspirin (81–300 mg). There were no significant differences between the groups in the incidence of VTE (OR: 1.21, 95% CI: 0.72–2.01), PE (OR: 1.01, 95% CI: 0.39–2.61), asymptomatic DVT (OR: 1.39, 95% CI: 0.64–3.00), suspected DVT (OR: 1.13, 95% CI: 0.49–2.61) and major bleeding (OR: 0.84, 95% CI: 0.55–1.27). Discussion: Aspirin is as effective as rivaroxaban for primary thromboprophylaxis post‐THA and TKA, without increased incidence of complications. Further research is needed to determine the optimal dosing regimen of aspirin and its long‐term efficacy in preventing VTE. Level of Evidence: Level I. [ABSTRACT FROM AUTHOR]

Oral anticoagulant therapy (OAT) for managing atrial fibrillation (AF) encompasses vitamin K antagonists (VKAs, such as warfarin), which was the mainstay of anticoagulation therapy before 2010, and direct-acting oral anticoagulants (DOACs, namely dabigatran etexilate, rivaroxaban, apixaban, edoxaban), approved for the prevention of AF stroke over the last thirteen years. Due to the lower risk of major bleeding associated with DOACs, anticoagulant switching is a common practice in AF patients. Nevertheless, there are issues related to OAT switching that still need to be fully understood, especially for patients in whom AF and heart failure (HF) coexist. Herein, the effective impact of the therapeutic switching from warfarin to DOACs in HF patients with AF, in terms of cardiac remodeling, clinical status, endothelial function and inflammatory biomarkers, was assessed by a machine learning (ML) analysis of a clinical database, which ultimately shed light on the real positive and pleiotropic effects mediated by DOACs in addition to their anticoagulant activity. [ABSTRACT FROM AUTHOR]

Falls are one of the most fearsome events in anticoagulated older adults. The evidence concerning safety of direct oral anticoagulants (DOACs) in falling elderly patients with atrial fibrillation (AF) is still limited. We prospectively enrolled consecutive anticoagulant-naïve patients aged 65 years and older, starting anticoagulation with DOACs for AF. The study cohort was stratified in fallers vs. non-fallers, according to the occurrence of at least one fall during the 2-year follow-up and bleeding outcomes were evaluated. We enrolled 524 consecutive patients. Mean age was 80.8 years and they were mostly women (54.0%). Among the study cohort, 148 patients (28.2%) presented at least one fall episode during the study period. After the adjustment for potential confounders, no difference was found between fallers and non-fallers for all the study outcomes: major bleeding [HR: 1.04 (95%CI: 0.58–1.85)], intracranial haemorrhage [HR: 1.63 (95%CI: 0.69–3.80)], clinically relevant non-major bleeding [HR: 1.21 (95%CI: 0.83–1.76)], and all-cause death [HR: 1.51 (95%CI: 0.85–2.69)]. The presence of a prior cerebrovascular event [HR: 2.27 (95%CI: 1.12–4.62); p-value: 0.02] and polypharmacy [HR: 1.60 (95%CI: 1.08–2.39); p-value: 0.02] were the main drivers for major and clinically relevant non-major bleedings, respectively. Falls in an anticoagulant-naïve population aged 65 years and over starting a DOAC for AF do not increase the bleeding risk. Thus, the presence of falls should not discourage clinicians from prescribing DOACs also in this subset of patients. • Safety of DOACs in older adults with AF and falls was evaluated. • Falls did not increase the bleeding risk in older adults with AF on DOACs. • The presence of falls should not dissuade from prescribing DOACs in this population. • DOACs dose reduction should be adopted only when the appropriate criteria are met. • Cerebrovascular events and polypharmacy showed to be key predictors of bleeding. [ABSTRACT FROM AUTHOR]

Purpose: Direct oral anticoagulants (DOACs) have been approved, for over a decade, by both European and American medicine agencies, for treatment and prevention of several cardiovascular conditions. Since then, an increasing amount of data has been added to the medical literature day by day, resulting in a dichotomy in selection of the appropriate agent, dosage, and duration of treatment for special populations with multiple comorbidities. Considering these issues, we have prepared a comprehensive review for the clinical practitioner, to optimize the DOAC utilization in clinical practice. Methods: A thorough literature search and review was conducted, concerning mainly the last decade. Our review focused on the current guidelines and the most recently published studies in PubMed, Science Direct Scopus, and Google Scholar to date. Conclusion: The purpose of this study is to provide guidance for healthcare professionals for making proper decisions when confronted with clinical challenges. Nevertheless, further research is required to establish DOAC superiority in complicated cases, where there is clinical uncertainty. [ABSTRACT FROM AUTHOR]

In clinical practice, the number of patients treated with direct oral anticoagulants (DOACs) has consistently increased over the years. Since anticoagulant therapy has been associated with an annual incidence of major bleeding (MB) events of approximately 2% to 3.5%, it is of paramount importance to understand how to manage anticoagulated patients with major or life-threatening bleeding. A considerable number of these patients' conditions necessitate hospitalization, and the administration of reversal agents may be imperative to manage and control bleeding episodes effectively. Importantly, effective strategies for reversing the anticoagulant effects of DOACs have been well recognized. Specifically, idarucizumab has obtained regulatory approval for the reversal of dabigatran, and andexanet alfa has recently been approved for reversing the effects of apixaban or rivaroxaban in patients experiencing life-threatening or uncontrolled bleeding events. Moreover, continuous endeavors are being made to develop supplementary reversal agents. In emergency scenarios where specific reversal agents might not be accessible, non-specific hemostatic agents such as prothrombin complex concentrate can be utilized to neutralize the anticoagulant effects of DOACs. However, it is paramount to emphasize that specific reversal agents, characterized by their efficacy and safety, should be the preferred choice when suitable. Moreover, it is worth noting that adherence to the guidelines for the reversal agents is poor, and there is a notable gap between international recommendations and actual clinical practices in this regard. This narrative review aims to provide physicians with a practical approach to managing specific reversal agents. [ABSTRACT FROM AUTHOR]

Background: Anticoagulation for venous thromboembolism (VTE) is required for at least three to six months; however, it is advisable to extend the duration in certain cases, in which case a reduced dose of Direct Oral Anticoagulants (DOACs) may be an option. Our objective was to investigate the efficacy and safety of reduced-dose DOACs in extended anticoagulation treatment compared to full doses. Methods and Results: This retrospective single-centre study included 185 patients treated with DOACs for at least 6 months who were divided into two groups: (1) the Full Dose (FD) group (n = 113) and (2) the Reduced Dose (RD) group (n = 72), which included patients treated with Apixaban at 2.5 mg bis in die (BID) and Rivaroxaban at 10 mg once daily (OD). Post-thrombotic syndrome (PTS) and its progression were evaluated. During an overall follow-up of 48.32 ± 29.49 months, no VTE occurred, and no patients experienced major bleeding; clinically relevant non-major bleeding occurred in three patients in each group (2.7% vs. 4.2% in FD vs. RD, respectively, p = 0.57). From baseline to follow-up, the prevalence of PTS was not significantly decreased in either group (FD: 54.9% vs. 51.3%, p = 0.29; RD 51.4% vs. 44.4%, p = 0.12); conversely, the Villalta score values were significantly decreased at the last follow-up (FD: 5.51 ± 4.18 vs. 5.51 ± 4.18, p < 0.001; RD 5.49 ± 4.06 vs. 5.11 ± 3.73, p = 0.006). Conclusion: In this real-world retrospective registry, very long-term extended anticoagulant therapy with DOACs at full or reduced doses showed comparable efficacy, safety, and impact on PTS progression. Larger studies are needed. [ABSTRACT FROM AUTHOR]

Introduction: Pulmonary embolism (PE) exerts a significant morbidity and mortality burden which is associated with major financial cost for healthcare systems and patients. Our study aims to estimate the PE outpatient pharmaceutical cost in Greece. Methods: This retrospective study was based on data provided by the National Organization for the Provision of Health Services of Greece (NPHO) concerning the electronic prescriptions that were issued during the period 2013–2017 for PE patients. The data were associated with treatment from a cohort of 200 PE patients from the PE Outpatient Clinic of the University Hospital of Larissa. The collected data included the active substances prescribed, the dosage, the duration of treatment, and the pharmaceutical cost reimbursed from NPHO for each patient. Results: During the study period, 101426 electronic prescriptions were collected by NPHO. The estimated total cost of the PE outpatient treatment was €65910 in 2013 and increased to €1585552 in 2017. In 2013, the cost was €580794 for injectables and €7851 for acenocumarol, while in 2017 the cost of rivaroxaban was €1122086, the cost of apixaban was €119243, the cost of injectables was €321062, the cost of dabigatran was €4343 and the cost of acenocumarol was €19818. Conclusions: The PE outpatient pharmaceutical cost has increased in recent years. This is mainly attributed to the wide implementation of direct oral anticoagulants (DOACs) for the treatment of PE. No definite conclusions about the total PE cost can be drawn since DOACs require fewer laboratory visits which may reduce the additional costs. [ABSTRACT FROM AUTHOR]

Background: The coronavirus pandemic has led to the creation of clinical guidelines by a large number of professional medical communities. However, the quality and methodology of development of Russian clinical guidelines has been little studied. The continued relevance of studying the use of DOACs (Direct oral anticoagulants) in patients with COVID-19 was the basis for conducting this study. Aim: The objective of this study was to assess DOAC consumption and expenditure in the Russian Federation during the COVID-19 pandemic and to analyze whether it was supported by the domestic evidence base for the use of DOACs in COVID-19 patients through identifying all publicly available Russian-produced CPGs (Clinical practice guidelines) for the treatment of COVID-19 and assessing their quality as the source of recommendations for the use of oral anticoagulants for the prevention of thrombotic complications in COVID-19 patients. We searched Russian databases for CPGs, published between 2020 and 2023. We identified seven relevant documents that met our inclusion criteria. Three authors analyzed Russian clinical guidelines using an AGREE II questionnaire. We calculated DOAC DDD (defined daily dose) consumption according to Russian clinical guidelines and DDD consumption in patients with COVID-19 for the period 2020–2022. Results: Seven clinical CPGs were analyzed with the AGREE II tool. It was revealed that experts gave the highest scores for the sections on scope and purpose (from 62.98% to 100%), and clarity of presentation (from 96.30% to 100%). The lowest scores were given for the sections on stakeholder involvement (33.33% to 64.81%), rigour of development (from 0% to 49.31%), applicability (from 23.61% to 50%), and editorial independence (from 0% to 50%). When comparing the total score, it was found that two clinical guidelines received the highest scores—ROPNIZ (Livzan), and ROPNIZ (Drapkina). The minimum score was registered with the NIIOZMM (Khripun) clinical guideline. No guideline received a total score of more than 70%. According to clinical recommendations, the consumption of apixaban and rivaroxaban is 15 DDD (30-day course of therapy), or 22.5 DDD (45-day course of therapy). Consumption of apixaban in the Russian Federation in 2020 and 2021 corresponds to the indicators presented in clinical recommendations (in 2020—26.59 DDD per patient with COVID-19; in 2021—15.75 DDD per patient with COVID-19), and in 2022—10.67 DDD, which is below the recommended values. In 2020, consumption of rivaroxaban in the Russian Federation was 26.59 which corresponds to data from clinical recommendations; in 2021, consumption decreased to 7.87 DDD; in 2022 it decreased to 5.48 DDD, which is 2.74 times less than recommended. Conclusions: Analysis of seven clinical recommendations revealed that such sections of clinical recommendations as scope, purpose, and clarity of presentation had the highest degree of assessment in accordance with AGREE II. The lowest scores were given for the sections on stakeholder involvement, rigour of development, applicability, and editorial independence. When comparing the total score, it was found that two clinical guidelines received the highest scores—the Russian Society for the Prevention of Non-communicable Diseases (Livzan), and the Russian Society for the Prevention of Non-communicable Diseases (Drapkina). The minimum score was registered with the Research Institute for Healthcare Organization and Medical Management of Moscow Healthcare Department clinical guideline. No guideline received a total score of more than 70%. During the pandemic, the highest DDD consumption of DOACs was in 2020, which exceeded the DOACs' recommended DDD by Russian clinical guidelines. DOAC consumption had decreased by 2022. There was a decrease in the consumption of rivaroxaban, with an increase in apixaban's share in the structure of DOAC consumption during the coronavirus pandemic. Obtained data indicate that in 2021 the apixaban consumption in the Russian Federation corresponded to the recommended DDD in the national guidelines, which indicates the most correct use of apixaban according to Russian GPGs. [ABSTRACT FROM AUTHOR]

Abstract Introduction Venous thromboembolisms (VTEs), including deep vein thrombosis (DVT) and pulmonary embolisms (PE), are common after total knee (TKA) and hip arthroplasty (THA). Recent studies suggest that aspirin effectively prevents VTE following major orthopaedic surgery. This meta‐analysis compares randomised controlled trials (RCTs) evaluating aspirin versus direct oral anticoagulants (DOACs) for VTE prevention after primary THA and TKA. Methods We included RCTs from 2017 to 2023 that looked at aspirin versus DOACs for VTE prophylaxis in primary THA and TKA. A search strategy was conducted which used Boolean operators and MESH terms. Primary outcomes included VTE rates, symptomatic, asymptomatic DVT and PE. Secondary outcomes were mortality and bleeding complications. Statistical analysis was performed using REVMAN software. An odds ratio with a 95% confidence interval was generated for the pooled studies. Heterogeneity was assessed using the I2 variable, and publication bias was evaluated with a funnel plot. Results Seven RCTs with 3967 patients were included for analysis. Rivaroxaban 10 mg OD was compared to varying doses of aspirin (81–300 mg). There were no significant differences between the groups in the incidence of VTE (OR: 1.21, 95% CI: 0.72–2.01), PE (OR: 1.01, 95% CI: 0.39–2.61), asymptomatic DVT (OR: 1.39, 95% CI: 0.64–3.00), suspected DVT (OR: 1.13, 95% CI: 0.49–2.61) and major bleeding (OR: 0.84, 95% CI: 0.55–1.27). Discussion Aspirin is as effective as rivaroxaban for primary thromboprophylaxis post‐THA and TKA, without increased incidence of complications. Further research is needed to determine the optimal dosing regimen of aspirin and its long‐term efficacy in preventing VTE. Level of Evidence Level I.

Background: Dementia is a recognized complication of atrial fibrillation (AF). Oral anticoagulant (OAC) therapy can potentially be protective against this complication. Methods: A comprehensive search of MEDLINE and Embase for comparative observational studies reporting the efficacy of OAC therapy for the incidence of dementia in patients with AF was conducted from its inception until March 2023. Studies that had patients with prior use of OAC or with a previous history of dementia were excluded. Results: A total of 22 studies were included in this review involving 617,204 participants. The pooled analysis revealed that OAC therapy, including direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs), was associated with a reduced incidence of dementia in AF patients. Specifically, compared to non-OAC treatment, OACs demonstrated a significant reduction in dementia incidence (HR 0.68, 95 % CI [0.58, 0.80], p

The aim of the study was to investigate the dynamics of inpatient consumption of direct oral anticoagulants in different regions of the Russian Federation for the period from 2017 to 2022.Materials and methods. This study is a non-interventional, retrospective analysis of the electronic database records of Cursor Marketing LLC (Russia) about the announced by medical organizations and executed contracts for the purchase of direct oral anticoagulants (DOACs). The сonsumption was calculated on the basis of a DDD (defined-daily-dose) and estimated DDDTID (defined-daily-dose/1000-inhabitants/day) for each DOACs: rivaroxaban, dabigatran and apixaban. The Rosstat database available on its official website were used as a source of inhabitants data for the Russian regions.Results. A total of 57 866 records were entered into the analyzed databases of Cursor Marketing LLC (Russia) from 2017 to 2022, 47.38% of which indicated rivaroxaban as the drug being procured, 26.51% indicated dabigatran, and 26.11% indicated apixaban. Edoxaban was not procured by healthcare organizations. During the period investigated, there was an increase in the consumption of all DOACs studied, with a higher increase for apixaban (by an average of 284.6% per year), then rivaroxaban (by 144.8% per year) and, to a lesser extent, dabigatran (by 92.5% per year). The analysis of DOACs consumption in general showed that compared to 2017, the need for these drugs in medical organizations in 2022 increased by 18 times. The Urals Federal District consistently exceeds the national average in terms of DDTID consumption. Noteworthy is the consumption dynamics of the regions of the Central Federal District and the North-Western Federal District, which made it possible to achieve DDDTID values above the national average for 5 out of 6 observation years. The lowest rates of DOACs consumption were observed in the Volga Federal District, which, despite positive growth dynamics, failed to reach the national average values. A high level of consumption (>10 DDDTID) of rivaroxaban was noted for the Arkhangelsk region (2018) and the Nenets Autonomous District (in 2021), dabigatran – only for the Arkhangelsk region (in 2018). Many more regions reached high levels of the apixaban consumption, especially in 2021.Conclusion. Despite a number of limitations, the data on the volume of DOACs procurement can be used in the analysis of the consumption at both regional and national levels. When analyzing the DOACs consumption, the impact of COVID-19 pandemic and pharmacogenetic features of patients in different regions should be taken into account. During the studied period of time, a significant part of the Russian regions achieved a consumption level of rivaroxaban and apixaban, but not dabigatran, exceeding 1 DDDTID.

Abstract Background There are limited data about the clinical benefits and harm of direct oral anticoagulants (DOACs) in stroke prevention in patients with atrial fibrillation (AF) complicated with anemia or thrombocytopenia. Methods This is a multi-center retrospective cohort study involving 5469 AF patients from 15 hospitals in China. Patients were divided into three groups according to hemoglobin and platelet levels: Group 1 (hemoglobin male ≥ 130 g/L; female ≥ 120 g/L and platelet ≥ 100 × 109/L), Group 2 (hemoglobin male

Background: Direct oral anticoagulants (DOACs) cause unwanted interference in various hemostasis assays, including lupus anticoagulant (LA) testing, where false positive and false negative identification may occur. DOAC Stop (DS) is an activated charcoal (AC) product used to specifically and effectively adsorb DOACs from test plasma. This process normally requires plasma treatment, centrifugation and plasma separation prior to tests, but inexperienced operators may also inadvertently transfer residual AC particles, thereby potentially adversely affecting clot detection. Methods: We hypothesized that residual DS might not be problematic for mechanical clot detection. We therefore investigated the potential impact of DS and a new DS liquid (DS-L) product on clotting tests using a mechanical clot detection system. Varying concentrations of DS were added to normal and abnormal plasmas with and without DOAC presence. Clotting tests including PT, APTT and dRVVT were performed directly in the analyzer without plasma/DS centrifugation. Results: DS up to double the recommended treatment level had only minor effects on all test results, despite completely obscuring visibility in the plasma/reagent mix. This confirms that the centrifugation step may be able to be omitted when using mechanical detection systems. Conclusions: Should DS carryover into treated plasmas occur, this should not cause issues with testing performed on mechanical clot-sensing devices. Moreover, we hypothesize that DS can be used directly in these systems, without the need for centrifugation, thereby simplifying its many potential applications. [ABSTRACT FROM AUTHOR]

Introduction: Risk stratification in heart failure (HF) is essential for clinical and therapeutic management. The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score is a validated prognostic model for assessing cardiovascular risk in HF patients with reduced ejection fraction (HFrEF). From the validation of the score, the prevalence of HF patients treated with direct oral anticoagulants (DOACs), such as edoxaban, for non-valvular atrial fibrillation (NVAF) has been increasing in recent years. This study aims to evaluate the reliability of the MECKI score in HFrEF patients treated with edoxaban for NVAF. Materials and Methods: This study included consecutive outpatients with HF and NVAF treated with edoxaban (n = 83) who underwent a cardiopulmonary exercise test (CPET). They were matched by propensity score with a retrospective group of HFrEF patients with NVAF treated with vitamin K antagonists (VKAs) from the MECKI score registry (n = 844). The study endpoint was the risk of cardiovascular mortality, urgent heart transplantation, or Left Ventricle Assist Device (LVAD) implantation. Results: Edoxaban patients were treated with a more optimized HF therapy and had different clinical characteristics, with a similar MECKI score. After propensity score, 77 patients treated with edoxaban were successfully matched with the MECKI-VKA control cohort. In both groups, MECKI accurately predicted the composite endpoint with similar area under the curves (AUC = 0.757 vs. 0.829 in the MECKI-VKA vs. edoxaban-treated group, respectively, p = 0.452). The two populations' survival appeared non-significantly different at the 2-year follow-up. Conclusions: this study confirms the prognostic accuracy of the MECKI score in HFrEF patients with NVAF treated with edoxaban, showing improved predictive power compared to VKA-treated patients. [ABSTRACT FROM AUTHOR]

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Introduction: Although direct oral anticoagulants' (DOACs) prescriptions have experienced immense growth in the last decade, the proportion of discontinuers is still common yielding an increased risk of ischemic stroke (IS) onset. Aims: We aimed to estimate the association between DOACs discontinuation and risk of IS among patients with non‐valvular atrial fibrillation (NVAF). Methods: We used data from a cohort of new DOACs users, followed patients from the first DOAC prescription date up to IS (index date) and conducted a nested case–control analysis using conditional logistic regression. Adjusted odds ratios, 95% confidence intervals were calculated for discontinuation of DOACs (current use compared with past use). The latter, subdivided among those stopping treatment 3 to 2 months and 6 and 3 months prior to index date. The effect of naïve current users against IS onset compared with non‐naïve current users was also evaluated. Results: DOACs discontinuation showed an OR of IS of 1.47 (95% CI: 1.02–2.12); estimates were 2.51 (95% CI: 1.84–3.42) for whom discontinued treatment within months 3 and 2 and 1.43 (95% CI: 0.96–2.13) for those between months 6 and 3 prior to index date. Analyzing DOACs individually, risk of IS associated with past users compared with current users: 1.98 (95% CI: 1.25–3.12) for apixaban, 1.38 (95% CI: 0.40–4.72) for edoxaban, 1.98 (95% CI: 1.24–2.65) for dabigatran and 1.87 (95% CI: 1.26–2.76) for rivaroxaban. Similar results were found when stratified by naïve and non‐naïve users. Conclusions: DOACs' discontinuation is associated with higher risk of IS, especially in the second and third months following interruption. [ABSTRACT FROM AUTHOR]

Objective: Direct oral anticoagulants (DOACs) are first-line therapy for stroke prevention for 1.4 million atrial fibrillation (AF) patients in the UK. However, the rates of DOAC dosing below evidence-based recommendations are estimated between 9% and 22%. This study explores specific patient and physician factors associated with prescribing inappropriate DOAC underdoses. Methods: DOAC-prescribing physicians within the UK completed both a clinical vignette survey, which contained 12 hypothetical patient profiles designed to replicate DOAC prescribing scenarios, and a physician survey to capture sociodemographic, clinical experience, and prescriberrelated beliefs and motivations related to DOAC prescribing. Eight patient factors based on a literature search and an expert consultation process were varied within the vignettes. Associations between the prescribers' dosing choices and patient factors were explored via multilevel logistic regression. The analysis is focused on the most frequently selected DOACs, apixaban and rivaroxaban, both of which have different dosing guidelines. Results: In all, 336 prescribers (69% male; 233/336) completed the survey, mostly general physicians (GPs) (45%) or cardiology specialists (36%) with a mean of 17.9 years' experience. Most prescribers (73%; 244/336) inappropriately underdosed at least once; rates between GPs and specialists were nearly identical. Patient factors most strongly associated with apixaban inappropriate underdosing included a history of major bleeding and falls. For rivaroxaban, these were major bleeding and severe frailty. Only 32% (106/335) of prescribers reported DOAC dosing guidelines as the sole influence on their prescribing behaviour. Among prescribers who did not inappropriately underdose, greater prescribing confidence was aligned to increased perception of inappropriate underdose risk. Conclusions: Overall, patient factors such as major bleeding and severe frailty were found to be associated with inappropriate underdosing of apixaban and rivaroxaban. Furthermore, prescribers who were more confident in DOAC prescribing, and were more worried about the risk of stroke, were significantly less likely to inappropriately underdose. These findings suggest that all prescribers, regardless of speciality, may benefit from education and training to raise awareness of the risks associated with inappropriate DOAC underdosing. [ABSTRACT FROM AUTHOR]

Annemarie Voss,1 Bianca Kollhorst,2 Katharina Platzbecker,1 Ute Amann,1 Ulrike Haug1,3 1Department of Clinical Epidemiology, Leibniz Institute for Prevention Research and Epidemiology – BIPS, Bremen, Germany; 2Department of Biometry and Data Management, Leibniz Institute for Prevention Research and Epidemiology – BIPS, Bremen, Germany; 3Faculty of Human and Health Sciences, University of Bremen, Bremen, GermanyCorrespondence: Ulrike Haug, Department of Clinical Epidemiology, Leibniz Institute for Prevention Research and Epidemiology – BIPS, Bremen, Germany, Tel +49 421 218 56862, Email haug@leibniz-bips.dePurpose: Over the last decade, the use of direct oral anticoagulants (DOACs) has strongly increased. We aimed to describe and compare risk profiles including potential changes over time among persons with non-valvular atrial fibrillation initiating treatment with different DOACs or phenprocoumon (vitamin K antagonist) between 2011 and 2019 in Germany.Patients and Methods: Using the German Pharmacoepidemiological Research Database (GePaRD; claims data of ~20% of the German population), we identified persons with a first dispensing of phenprocoumon or a DOAC and a diagnosis of non-valvular atrial fibrillation between August 2011 and December 2019. We described the morbidity of included patients prior to treatment initiation, stratified by year of treatment initiation.Results: Overall, we included 448,028 new users (phenprocoumon: N = 118,117, rivaroxaban: N = 130,997, apixaban: N = 130,300, edoxaban: N = 38,128, dabigatran: N = 30,486). Comparing new DOAC users in 2019, the proportion with prior ischemic stroke was highest for dabigatran (17%) and lowest for rivaroxaban (8%). The proportion with prior major bleeding was also highest for dabigatran (25%) and lowest for edoxaban (20%). New users of apixaban were oldest and, eg, showed the highest prevalence of congestive heart failure. Changes over time were most pronounced for phenprocoumon. For example, among persons initiating phenprocoumon in 2012 vs 2019, the proportion with prior major bleeding increased from 18% to 35%; the proportion with renal disease increased from 20% to 36% and the proportion with liver disease from 18% to 24%.Conclusion: This study demonstrated differences in risk profiles between new users of different oral anticoagulants and substantial changes over time among new phenprocoumon users. These differences have to be considered in head-to-head comparisons of these drugs based on observational data, especially regarding potential unmeasured confounding.Keywords: atrial fibrillation, oral anticoagulants, direct oral anticoagulants, DOACs, risk profiles

Nephrotic syndrome (NS) is one of the common presentations of kidney diseases both in children and adults. NS patients, particularly those with membranous nephropathy, have increased risk of thromboembolic events. Heparin and vitamin K antagonists (VKAs) continue to be commonly used as prophylactic and therapeutic agents, given the experience of use of these agents in NS and nonrenal indications of anticoagulation. The use of direct oral anticoagulants (DOACs) in NS is reported in some case series, conference abstracts, and a few small studies. We report our experience of using DOACs in 11 patients of NS with severe hypoalbuminemia. Out of 11, one patient required change of anticoagulation from DOACs to VKA and the rest of them did well with DOACs. There were no bleeding episodes in our study. We suggest larger studies to be carried out to better understand the use of these agents in NS. [ABSTRACT FROM AUTHOR]

Thrombosis is a common and serious event in cancer patients. While risk factors are well established in solid tumors and have lead to guidance regarding prophylaxis, similar data and recommendations are lacking for patients with hematologic malignancies. Likewise treatment for established venous thrombosis in cancer patients has shifted from low molecular weight heparin to direct oral anticoagulants (DOACs) based on favorable outcomes with the latter drugs in most tumor types while hematologic malignancies remain understudied and the appropriateness of DOAC use in these patients is less certain. Reasons for the knowledge gaps that have developed regarding management of thrombosis in hematologic malignancies include their relative rarity compared to solid organ cancer making large scale trials difficult to complete, and the particular nature of blood cancers and their treatment giving rise frequently to severe thrombocytopenia which is typically regarded as an exclusion from clinical trials.In this review we discuss landmark studies and other available literature regarding management of thromboembolism in hematologic malignancies and highlight unique features of these diseases and their treatment in this context.

IntroductionThe guidelines' recommendations for anticoagulation in cancer patients with catheter-related thrombosis are unclear. The aim of this systematic review was to assess anticoagulation management in cancer patients with catheter-related thrombosis (CRT) based on previously published studies.MethodsAs of June 10, 2023,we searched databases including PubMed, Embase, and Cochrane and included 11 observational studies that met the criteria. We evaluated 770 adults with active cancer and objectively confirmed patients with CRT who were using drugs including warfarin, LMWH, and new oral anticoagulants as antithrombotic therapy.ResultsWe extracted outcome data, including thrombosis recurrence, catheter dysfunction, major bleeding, and death, and performed a meta-analysis.DiscussionIn this study we found that the risk of VTE recurrence was higher with rivaroxaban, the risk of bleeding and death appeared to be greater with warfarin, and although the risk of catheter dysfunction due to LMWH is a concern, it is still a more reasonable option for cancer patients with catheter-related thrombosis.Systematic Review Registrationhttp://www.clinicaltrials.gov, identifier (CRD42022367979).

ABSTRACTObjective Direct oral anticoagulants (DOACs) are first-line therapy for stroke prevention for 1.4 million atrial fibrillation (AF) patients in the UK. However, the rates of DOAC dosing below evidence-based recommendations are estimated between 9% and 22%. This study explores specific patient and physician factors associated with prescribing inappropriate DOAC underdoses.Methods DOAC-prescribing physicians within the UK completed both a clinical vignette survey, which contained 12 hypothetical patient profiles designed to replicate DOAC prescribing scenarios, and a physician survey to capture sociodemographic, clinical experience, and prescriber-related beliefs and motivations related to DOAC prescribing. Eight patient factors based on a literature search and an expert consultation process were varied within the vignettes. Associations between the prescribers’ dosing choices and patient factors were explored via multilevel logistic regression. The analysis is focused on the most frequently selected DOACs, apixaban and rivaroxaban, both of which have different dosing guidelines.Results In all, 336 prescribers (69% male; 233/336) completed the survey, mostly general physicians (GPs) (45%) or cardiology specialists (36%) with a mean of 17.9 years’ experience. Most prescribers (73%; 244/336) inappropriately underdosed at least once; rates between GPs and specialists were nearly identical. Patient factors most strongly associated with apixaban inappropriate underdosing included a history of major bleeding and falls. For rivaroxaban, these were major bleeding and severe frailty. Only 32% (106/335) of prescribers reported DOAC dosing guidelines as the sole influence on their prescribing behaviour. Among prescribers who did not inappropriately underdose, greater prescribing confidence was aligned to increased perception of inappropriate underdose risk.Conclusions Overall, patient factors such as major bleeding and severe frailty were found to be associated with inappropriate underdosing of apixaban and rivaroxaban. Furthermore, prescribers who were more confident in DOAC prescribing, and were more worried about the risk of stroke, were significantly less likely to inappropriately underdose. These findings suggest that all prescribers, regardless of speciality, may benefit from education and training to raise awareness of the risks associated with inappropriate DOAC underdosing.

Background: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia type. Patients with AF are often administered anticoagulants to reduce the risk of ischemic stroke due to an irregular heartbeat. We evaluated the efficacy and safety of edoxaban versus warfarin in patients with nonvalvular AF by conducting an updated meta-analysis of real-world studies. Methods: In this comprehensive meta-analysis, we searched two databases, PubMed and EMBASE, and included retrospective cohort observational studies that compared edoxaban with warfarin in patients with nonvalvular AF from 1 January 2009, to 30 September 2023. The effectiveness and safety outcomes were ischemic stroke and major bleeding, respectively. In the final analysis, six retrospective observational studies involving 87,236 patients treated with warfarin and 40,933 patients treated with edoxaban were included. To analyze the data, we used a random-effects model to calculate the hazard ratio (HR). Results: Patients treated with edoxaban had a significantly lower risk of ischemic stroke [hazard ratio (HR) = 0.66; 95% confidence interval (CI) = 0.61-0.70; p < 0.0001] and major bleeding (HR = 0.58; 95% CI = 0.49-0.69; p < 0.0001) than those treated with warfarin. The sensitivity analysis results for ischemic stroke and major bleeding were as follows: HR = 0.66; 95% CI = 0.61-0.70; p < 0.0001 and HR = 0.58; 95% CI = 0.49-0.69; p < 0.0001, respectively. Conclusion: Our findings revealed that edoxaban performed better than warfarin against major bleeding and ischemic stroke. [ABSTRACT FROM AUTHOR]

Background: There are limited data about the clinical benefits and harm of direct oral anticoagulants (DOACs) in stroke prevention in patients with atrial fibrillation (AF) complicated with anemia or thrombocytopenia. Methods: This is a multi-center retrospective cohort study involving 5469 AF patients from 15 hospitals in China. Patients were divided into three groups according to hemoglobin and platelet levels: Group 1 (hemoglobin male ≥ 130 g/L; female ≥ 120 g/L and platelet ≥ 100 × 109/L), Group 2 (hemoglobin male < 130 g/L; female < 120 g/L or platelet < 100 × 109/L), and Group 3 (hemoglobin male < 130 g/L; female < 120 g/L and platelet < 100 × 109/L). Patients in each category are further divided into two groups according to their stroke prevention strategies: rivaroxaban or dabigatran. Clinical results include major, minor, total bleeding, thrombosis, and the composite outcome of major bleeding and thrombosis. Results: Higher hemoglobin levels were associated with a reduced risk of total bleeding and major bleeding, while platelet counts were not associated with any event. Compared with Group 1, Group 2 had a higher risk of major bleeding (aOR 1.70, 95%CI 1.12–2.57, P = 0.012), and the composite endpoint of major bleeding and thrombosis (aOR 1.70, 95%CI 1.19–2.44, P = 0.004). Compared with Group 1, Group 3 had a higher total bleeding risk (aOR 2.15, 95%CI 1.14–4.05, P = 0.018). Compared with dabigatran, rivaroxaban was associated with higher composite risk in Group 1 (aOR 2.91, 95% CI 1.66–5.16, P < 0.001) and Group 2 (aOR 3.05, 95%CI 1.46–6.39, P = 0.003), but there was no significant difference in Group 3 (aOR 1.78, 95%CI 0.23—13.54, P = 0.577). Conclusions: Higher hemoglobin levels are associated with a reduced risk of total bleeding and major bleeding in patients with AF. Dabigatran was associated with better clinical outcomes than rivaroxaban in patients with anemia or thrombocytopenia but not in those with anemia and thrombocytopenia. [ABSTRACT FROM AUTHOR]

Background: Little evidence is available on the long-term efficacy and safety of edoxaban, mainly due to the recent release date. The primary objective of the study was to evaluate the safety of edoxaban, defined by the incidence of major bleedings. We then aimed to evaluate the incidence of thromboembolic events and the persistence of edoxaban therapy in the long-term. Methods: In this observational cohort study, we included ischemic stroke patients enrolled in a previous study to evaluate the safety and efficacy of long-term edoxaban treatment. Data were collected by a trained investigator through a structured telephone interview. Results: Sixty-three subjects (median age 81.0 (73.5–88.0) years, 38.1% male) were included in the study, with a mean follow-up of 4.4 ± 0.7 years (range: 3.2–5.5 years). Only one patient (1.6%, 0.4%/year) presented a major extracranial bleeding, and none had cerebral hemorrhage. Six thromboembolic events occurred in five patients (7.9%): three recurrent strokes, two transient ischemic attacks, and one myocardial infarction (2.2%/year). Over a follow-up period of more than three years, 13 patients discontinued edoxaban (20.6%). Conclusions: Edoxaban seems to be effective and safe in the long-term. The persistence rate of edoxaban therapy is optimal after more than three years of treatment. [ABSTRACT FROM AUTHOR]

Direct factor Xa inhibitors have been extensively prescribed for multiple indications; however, hemodialysis patients have been excluded from most of the randomized controlled trials (RCTs) of direct factor Xa inhibitors. Therefore, the efficacy and safety of direct factor Xa inhibitors versus vitamin K antagonists (VKAs) in hemodialysis patients is uncertain. A systematic review and meta-analysis of RCTs was conducted by systematically searching PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane through November 25, 2022. We used the fixed-effect model to pool the risk ratio (RR) with a 95% confidence interval (CI). RevMan v5.4 software was used to pool dichotomous outcomes using RR and continuous outcomes using mean difference presented with the corresponding CI. Three RCTs with a total of 341 patients were included in our analysis. There was no difference between direct factor Xa inhibitors and VKAs regarding all-cause mortality (RR, 0.99; 95% CI [0.76, 1.30]; P = 0.96), cardiovascular mortality (RR, 1.35; 95% CI [0.71, 2.60]; P = 0.36), noncardiovascular mortality (RR, 0.75; 95% CI [0.53, 1.05]; P = 0.09), sudden mortality (RR, 1.33; 95% CI [0.53, 3.33]; P = 0.54), any cerebrovascular event (RR, 0.52; 95% CI [0.21, 1.29]; P = 0.16), ischemic stroke (RR, 0.51; 95% CI [0.19, 1.37]; P = 0.18), and hemorrhagic stroke (RR, 0.61; 95% CI [0.10, 3.70]; P = 0.59). In patients with atrial fibrillation who are on hemodialysis, direct factor Xa inhibitors and VKAs were similar in terms of efficacy and safety outcomes. However, evidence is still sparse, warranting dedicated RCTs. [ABSTRACT FROM AUTHOR]

• DOACs provide a predictable anticoagulant effect with fewer drug interactions, thereby simplifying anticoagulation management. • The use of DOACs may help reduce the incidence of bleeding complications and associated morbidity and mortality. • This work focuses on the patient centered outcomes comparing the use of DOACs (prehospital) vs. conventional anticoagulation. The last decade has witnessed significant advancements in direct oral anticoagulants (DOACs), transforming the landscape of anticoagulation therapy. With the uptrend in DOACs use, critical care physicians are encountering more patients with pre-hospital DOACs prescription. Safety and real world outcomes-related data on DOACs use in critically ill patients are scarce. We assess the risk of major bleeding (MB) events and patient-centered outcomes with pre-hospital use of direct oral anticoagulant agents (DOACs) compared to warfarin therapy. Observational study in a single large academic center from January 1st, 2012, through May 4th, 2018. We included adult critically ill patients with warfarin or one of the DOACs, as active medications at the time of hospital admission. The primary outcome was major bleeding (MB), based on the ISTH criteria 99,481 patients were screened; 558 and 3037 patients were included in the final analysis for the DOAC and warfarin groups, respectively. Multivariable analysis showed that the pre-hospital use of DOACs was associated with lower odds for major bleeding events, GI bleeding, need for endoscopic intervention, hemorrhagic shock, any blood transfusion; but higher odds of intracranial bleeding, as compared to warfarin use. There was no difference in hospital length of stay or ICU-free days. Pre-hospital use of DOACs among critically ill patients is associated with lower major bleeding events, GI bleeding, need for endoscopic intervention, and blood transfusion but a higher risk for intracranial bleeding. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study aimed to assess the appropriateness of direct oral anticoagulants (DOACs) utilization in a Saudi tertiary hospital. PATIENTS AND METHODS: Adult inpatients and outpatients diagnosed with atrial fibrillation, deep vein thrombosis, or pulmonary embolism were included in a retrospective cohort study. Patients received at least one month of apixaban, rivaroxaban, or dabigatran. The duration of the study at the Armed Forces Hospital Southern Region in Khamis Mushait, Saudi Arabia, was from January 1, 2019, to December 31, 2021. The study assessed the appropriateness of DOACs dosing, initial and follow-up monitoring, the presence of clinically significant interactions, and treatment duration adherence. RESULTS: 778 patients were included in the analysis (mean age 71.34 ± 15.98 years, equal male and female representation). Rivaroxaban was administered to 40.8% of the patients, while apixaban and dabigatran were administered to 31.02% and 28.18% of the patients, respectively. The most prevalent indication for DOACs was atrial fibrillation (72.84%), followed by deep vein thrombosis and pulmonary embolism (27.16%). The most prevalent category of medication errors was inappropriate maintenance dose (41.7%), followed by inappropriate initial dose (37.97%) and lack of laboratory parameter monitoring (36.42%). 31.5 percent of the study sample lacked baseline renal functions, while 24.5% of patients lacked baseline liver functions. 115 patients (14.8%) had potential clinically significant interactions. Regarding treatment duration, 232 patients (29.8%) were improperly prescribed DOACs based on their indications. CONCLUSIONS: In a significant proportion of DOAC patients, the prescribed rational DOAC utilization parameters were not implemented. The results of the study provide specific improvement areas and objectives for Anticoagulation stewardship programs. [ABSTRACT FROM AUTHOR]

Introduction: Direct oral anticoagulants (DOACs) are underused in the elderly, regardless the evidence in their favour in this population. Methods: We prospectively enrolled anticoagulant-naïve patients aged ≥ 75 years who started treatment with DOACs for atrial fibrillation (AF) and stratified them in older adults (aged 75–84 years) and extremely older adults (≥ 85 years). Thrombotic and hemorrhagic events were evaluated for 12 months follow-up. Results: We enrolled 518 consecutive patients. They were mostly aged 75–84 years (299 patients; 57.7%) vs. ≥ 85 years (219 patients; 42.3%). Extremely older adults showed higher incidence of all the endpoints (systemic cardioembolism [HR 3.25 (95% CI 1.71–6.18)], major bleeding [HR 2.75 (95% CI 1.77–4.27)], and clinically relevant non-major bleeding [HR 2.13 (95% CI 1.17–3.92)]) vs. older adults during the first year after starting anticoagulation. In patients aged ≥ 85 years, no difference in the aforementioned endpoints was found between those receiving on-label vs. off-label DOACs. In the extremely older adults, chronic kidney disease, polypharmacy, use of antipsychotics, and DOAC discontinuation correlated with higher rates of thrombotic events, whereas a history of bleeding, Charlson Index ≥ 6, use of reduced DOAC dose, absence of a caregiver, use of non-steroidal anti-inflammatory drugs (NSAIDs), and HAS-BLED score ≥ 3 were associated with major bleedings. Conclusions: Naïve patients aged ≥ 85 who started a DOAC for AF are at higher risk of thrombotic and bleeding events compared to those aged 75–84 years in the first year of therapy. History of bleeding, HAS-BLED score ≥ 3 and use of NSAIDs are associated with higher rates of major bleeding. [ABSTRACT FROM AUTHOR]

Background: Direct oral anticoagulants (DOACs) are widely used for the treatment of venous thromboembolism (VTE) and for stroke prevention in atrial fibrillation (AF). However, evidence in obese and underweight patients is limited. We assessed the safety and effectiveness of DOACs and vitamin K antagonists (VKAs) in patients ≥ 120 kg or ≤ 50 kg enrolled in an observational prospective cohort study, the START-Register. Methods: Adult patients started on anticoagulant therapy were followed up for a median of 1.5 years (IQR 0.6–2.8). Primary efficacy outcome was the occurrence of VTE recurrence, stroke and systemic embolism. Primary safety outcome was major bleeding (MB). Results: 10,080 AF and VTE patients were enrolled between March 2011 and June 2021, 295 patients weighted ≤ 50 kg and 82 patients ≥ 120 kg. Obese patients were significantly younger than underweight patients. Rates of thrombotic events were low and similar between DOACs and VKAs in underweight patients (1 event on DOACs therapy [0.9% 95% CI 0.11–5.39] and 2 on VKAs [1.1% 95% CI 0.01–47.68]) and in overweight patients (0 events on DOACs, 1 on VKAs [1.6%, 95% CI 0.11–5.79]. Two MB events occurred on DOACs (1.9%, 95% CI 0.38–6.00) and 3 on VKAs (1.6%, 95% CI 0.04–22.06) in the underweight group; 1 MB on DOACs (5.3% 95% CI 0.33–16.68) and 2 on VKAs (3.3%, 95% CI 0.02–130.77) in the overweight group. Conclusions: DOACs seem to be effective and safe also for the treatment of patients with extreme body weights, both underweight and overweight. Further prospective studies are needed to support these findings. [ABSTRACT FROM AUTHOR]

Abstract Background Direct oral anticoagulants (DOACs) are considered high-risk medications and used to prevent thromboembolic events and stroke. This study aimed to examine patients’ views and experiences of DOACs use and factors that can promote safety associated with DOACs. Methods In-depth interviews were conducted with adult patients who had been prescribed DOACs, identified and invited by local collaborators in three different tertiary care hospitals in Saudi Arabia. A topic guide developed based on was used to inform the interview. Data were analysed thematically. Results Data saturation was achieved by the ninth participants. Three major themes were identified: (1) factors affecting DOAC's safety from the patients view; (2) barriers to adherence to DOACs and (3) strategies to promote the safety of DOACs. Lack of knowledge of DOACs, using inappropriate sources of information, lack of communication with HCPs, difficulty in having access to DOACs and lack of monitoring were the main factors affecting the safe use of DOACs. Unavailability of the drugs and difficulty in timely getting to hospitals affected adherence. Patients acknowledged difficulties communicating with healthcare professionals, timely access to anticoagulation clinics and in obtaining their DOACs on time. Conclusions There is a need to develop and evaluate theory-based interventions to promote patient knowledge, understanding and shared decision-making to optimise DOACs use and improve their safety.

Abstract A major advancement in the field of medicine has been the introduction and usage of direct oral anticoagulants (DOACs) such as dabigatran (Pradaxa), apixaban (Eliquis), and rivaroxaban (Xarelto). DOACs have been increasing in popularity for mainstay anticoagulation pharmacotherapy and are being preferred by physicians over warfarin due to their rapid onset, fewer drug and food interactions, and lack of frequent blood monitoring. DOACs have been indicated in the management of thromboembolic conditions and have been extensively researched in various medical trials and studies before the approval of dabigatran (Pradaxa) in 2010 by the FDA. DOACs, like warfarin, are associated with a risk of bleeding, requiring clearance of the drug from the bloodstream or administration of reversal agents. It is important for physicians to familiarize themselves with the various types of DOACs and their dosages, along with their advantages and disadvantages in comparison to other non-DAOC classes of medications before incorporating them into their patient management plans.