Search Results (97)

Background/Objectives: Venous thromboembolism (VTE) is an important global health concern associated with considerable morbidity and mortality. Despite established guidelines for VTE treatment, there is a gap between clinical recommendations and their implementation in practice because of limited accessibility, particularly in low- and middle-income countries and among patients with cancer. This study aimed to assess the cost-effectiveness of direct oral anticoagulants (DOACs) on VTE in patients with cancer at a Thai university-affiliated hospital. Methods: A cost–utility analysis using a Markov model was developed to estimate costs and quality-adjusted life-years (QALYs) of DOACs and low-molecular weight heparin (LWMH) in Thai patients with cancer aged over 60 years. The model with eight health states, including CAT on treatment, pulmonary embolism (PE), deep vein thrombosis (DVT), clinically relevant nonmajor bleeding (CRNMB), non-intracranial hemorrhage major bleeding (non-ICH MB), intracranial hemorrhage (ICH), off treatment, and any death, was developed with a one-month cycle length and used to estimate costs and health outcomes from a societal perspective with a lifetime horizon. The efficacy and safety of DOACs compared to LMWH were obtained from a network meta-analysis, while the costs were based on a Thai university hospital database. All costs and outcomes were discounted at 3%, and the Thai societal willingness-to-pay (WTP) threshold (THB 160,000 per QALY gained) was applied. The incremental cost-effectiveness ratio (ICER) was calculated to compare costs and QALYs of the interventions. Results: The total lifetime cost of LMWH was THB 70,928 (USD 2,163), while for apixaban, dabigatran, edoxaban, and rivaroxaban, the costs were THB 26,323 (USD 803), THB 33,667 (USD 1,027), THB 29,570 (USD 902), and THB 22,310 (USD 680), respectively. The QALYs for LMWH, apixaban, dabigatran, edoxaban, and rivaroxaban were 0.771, 0.775, 0.746, 0.759, and 0.770 QALYs, respectively. Compared to LMWH, apixaban provided 0.004 additional QALYs, with a decreased cost of THB 44,605 (USD 1,360), resulting in reduced expenses. On the other hand, dabigatran, edoxaban, and rivaroxaban were also associated with lower lifetime costs but reduced life-years and QALYs when compared with LMWH. Conclusions: This study revealed that apixaban is likely to be the preferred option for treating patients with CAT. However, policy decision-making process should take into account the uncertainties related to the implementation of this practice. Full article

Background/Objectives: Non-valvular atrial fibrillation (NVAF) is a common arrhythmia in the elderly and carries a high risk of cardioembolic stroke. Oral anticoagulation is central to prevention, with direct oral anticoagulants (DOACs) increasingly replacing warfarin due to better safety and convenience. However, major bleeding remains a key concern, particularly in older patients. This study aimed to determine the prevalence of major bleeding among elderly patients (≥65 years) with NVAF treated with oral anticoagulants. Methods: A retrospective cohort study was conducted on 886 elderly NVAF patients managed at a tertiary hospital between January 2012 and December 2023. Data on demographics, anticoagulant type, comorbidities, and bleeding events were collected. Associations between categorical variables were tested using Chi-square or Fisher’s exact tests, while logistic regression identified predictors of major bleeding. Results: The mean age was 78.4 ± 7.2 years, with equal gender distribution. Most patients (87.1%) received DOACs, while 12.9% were prescribed warfarin. A total of 63 patients (7.1%) experienced major bleeding, including 51 (6.6%) in the DOAC group and 12 (10.5%) in the warfarin group. Intracranial and intra-/retroperitoneal hemorrhages were most common. Logistic regression showed older age, prior bleeding, a higher HASBLED score, and antiplatelet use as significant predictors. Among patients with a recorded weight (n = 70), dosing adherence was better for apixaban and edoxaban compared to dabigatran and rivaroxaban. Conclusions: DOACs were associated with fewer major bleeding events than warfarin. Bleeding risk was strongly linked to age, prior bleeding, HASBLED score, and concomitant antiplatelet therapy, highlighting the importance of appropriate DOAC dosing for safety. Full article

Background/Objectives: While direct oral anticoagulants (DOACs) are widely used, robust evidence for low-energy trauma is scarce. Studies have shown similar or better outcomes of traumatic brain injury (TBI) under DOAC therapy compared to vitamin K antagonists, but there is limited data on the differences among DOAC types. Methods: We performed a retrospective study of TBI patients with pre-injury DOACs who presented to our level 1 trauma unit and received cranial computed tomography. Only low-energy trauma mechanisms were included. Results: We included 643 patients with an average age of 82 years. As per the Glasgow Coma Scale, 637 patients (99.1%) had a mild TBI and 34 patients (5.3%) had intracranial hematomas. No delayed intracranial bleeding occurred during in-hospital observation. Rivaroxaban was the most frequent DOAC (278, 43.2%), followed by apixaban (221, 34.4%), dabigatran (84, 13.1%), and edoxaban (60, 9.3%). Neurosurgical interventions were performed in three cases (0.5%). The head injury-related in-hospital mortality was 0.9% (six patients). Fisher’s Exact Test and regression analysis did not demonstrate statistically significant differences among the DOAC types regarding occurrence of intracranial bleeding, surgical interventions, or mortality. Conclusions: We found no statistically significant differences between DOACs regarding complications of TBI after low-energy trauma. This study shows an overall low risk of complications after low-energy trauma in a predominantly geriatric population with TBI and DOAC therapy. Full article

The prevalence of atrial fibrillation (AF) is increasing and often coexists with frailty. The management of anticoagulation therapy in frail older adults with AF is especially challenging due to the high risk of bleeding complications. The aim of this narrative review is to provide a comprehensive overview of current evidence about the management of anticoagulation in frail older adults with non-valvular AF. First, frailty itself should not be considered a contraindication. A comprehensive geriatric assessment is recommended to identify and potentially address conditions that may increase the risk of bleeding, such as inappropriately prescribed medications or malnutrition. Overall, the net clinical benefit remains in favour of oral anticoagulation in frail older adults, even if it decreases with increasing frailty severity. Direct Oral Anticoagulants (DOACs) show a better effectiveness and safety profile compared with Vitamin K antagonists (VKAs) in this population. Among DOACs, apixaban seems to be the safest. Also, edoxaban at a very low dosage (15 mg/day) could be an effective therapy in patients for whom the standard anticoagulation is contraindicated. Moreover, switching from VKAs to DOACs in frail older adults is a complex decision and should be personalized according to the stability of the ongoing anticoagulant therapy, the bleeding risk profile, and the severity of frailty. Finally, although further studies are required to confirm their effectiveness, factor XIa inhibitors are emerging as new promising alternative therapies because they have been associated with a lower bleeding risk compared with DOACs. Full article

Background/Objectives: Real-world data about clinical characteristics and edoxaban performance in patients with heart failure (HF) and atrial fibrillation (AF) are lacking. The EMAYIC study aimed to assess and compare the profile and cardiovascular outcomes in those patients according to HF subtypes based on left ventricular ejection fraction (LVEF). Methods: Multicentre, prospective (follow-up: 12 months), observational study. Consecutive adult patients were included at cardiology and internal medicine clinics across Spain with HF (NT-proBNP > 600 pg/mL) and AF, receiving edoxaban as per routine clinical practice. Incidence of major or clinically relevant non-major (CRNM) bleeding and composite of incidence of stroke or systemic embolism (SE) were assessed according to HF subtypes: reduced (HFrEF, LVEF < 40%), mildly reduced (HFmrEF, LVEF40–49%), and preserved (HFpEF, LVEF ≥ 50%) left ventricular ejection fraction. Results: Between March 2021 and January 2022, 497 patients were enrolled (HFrEF: 30.4%, HFmrEF: 17.3%, HFpEF: 52.3%). The median age was 76.3 years, 57.9% were male, and the mean CHA2DS2-VASc score was 4. A 60 mg edoxaban dose was prescribed in 70% of patients. The observed rate of bleeding was 6.6% (95% CI: 4.5–9.3%), without differences across HF subtypes (HFrEF: 7.5%, HFmrEF: 3.6%, HFpEF: 7.1%; p = 0.474). Intracranial bleeding occurred in one patient (HFrEF). Stroke occurred in seven patients (1.5%) (HFrEF: 3, HFmrEF: 1, HFpEF: 3), two cases of which were fatal (HFrEF: 1, HFpEF: 1). No SE events were reported. Cardiovascular death occurred in 19 patients (4.1%) (HFrEF: 4.8%, HFmrEF: 3.6%, HFpEF: 3.8%; p = 0.871). Conclusions: This study evidences a low incidence of major or CRNM bleeding in patients with HF and AF treated with edoxaban, regardless of HF subtype. Low rates of stroke (1.5%) and SE events (0%) were assessed. Full article

Heart Failure (HF) remains a major cause of mortality despite the advances in pharmacological treatment. Anticoagulation therapies, including Clopidogrel, Aspirin, Warfarin, and novel oral anticoagulants (NOACs) such as Apixaban, Rivaroxaban, Edoxaban, and Dabigatran, are frequently administered to HF patients to prevent thromboembolism and adverse, life-threatening outcomes (e.g., stroke and myocardial infarction). In these settings, drug resistance and variability in responsivity to therapeutic approaches are challenging issues. Recent studies suggest that non-coding RNAs, particularly microRNAs (miRs) may play a modulatory role in HF therapy context, affecting drug efficacy. Specific miRs have been associated with resistance to Clopidogrel (e.g., miR-223 and miR-26a), Aspirin (e.g., miR-19b-1-5p and miR-92a) and Warfarin (e.g., miR-133 and miR-137). Moreover, Digoxin, a cardiac glycoside acting also over bleeding risk, upregulates miR-132, which is involved in HF-associated cardiac alteration and hypertrophy. Evidence linking miR expression to NOAC pharmacodynamics, cardiac remodeling and regulation of the coagulation is growing. These findings highlight the need of deeply harnessing the potential of miRs as predictive biomarkers or therapeutic targets in HF. Improving the knowledge on the relationship between miR and anticoagulant drugs in HF patients will contribute to personalization of the anticoagulant therapies, aimed at enhancing patient responsivity and minimizing adverse effects, ultimately improving patient life quality. Full article

Background: Anticoagulation is the cornerstone of thromboembolic event prevention. Adversely, anticoagulants (ACs) are linked to a variety of adverse events. We aimed to assess the link between vitamin K antagonists (VKA) and direct anticoagulant (DOACs) use and acute kidney injury (AKI) using the FDA Adverse Events Reporting System (FAERS) Database. Methods: We conducted a disproportionality analysis on the adverse events (AEs) of interest in the FAERS database using the reporting odds ratio (ROR), proportional reporting ratio (PPR) with the Yates correction (x²yates), and the information component (IC). Results: A total of 20,253 cases of AKI associated with use of ACs were analyzed. Edoxaban, dabigatran and warfarin showed greater association with AKI (ROR 2.63; ROR 1.46; ROR). In cases with manifest bleeding, edoxaban, dabigatran, warfarin and rivaroxaban had a stronger statistical association with AKI. Rivaroxaban showed greater association with AKI compared to other ACs when used concomitantly with Aspirin (ROR 2.25). Conclusion: We showed increased odds of reporting AKI with use of edoxaban, dabigatran and warfarin compared to other anticoagulants. In cases with reported bleeding, AKI was more commonly reported with all five analyzed anticoagulants, except for apixaban, highlighting its favorable side-effect profile. Caution and clinical awareness are needed when prescribing ACs to vulnerable populations. Full article

Background: Deep learning methods may be useful for drug compound interaction and discovery analysis. However, there has been limited research on their use for screening biologically related adverse effects. Objectives: This study aims to pre-emptively screen for likely drug use persistence or success in clinical trials. Methods: This shall be achieved through the extension, application, and evaluation of a deep learning-based framework. Specifically, it shall be considered in the discovery of novel candidates and mechanisms underlying AF management-related adverse effects. The targets were linked to their adverse effects specified in two previous studies, their corresponding protein sequences, and the organs affected. Results: The new model showed good performance when compared to existing approaches in the Side Effect Resource (SIDER) and Food and Drug Administration Adverse Event Reporting System (FAERS) external validation datasets. A precision of 0.879 was obtained for enoxaparin, along with a recall of 0.746 for rivaroxaban. Stronger bleeding-related adverse effects were found for edoxaban compared with apixaban and enoxaparin. The binding and safety profiles of sequoiaflavone were very similar to those of rivaroxaban. Conclusions: This study presents a framework that could be used to pre-emptively screen for adverse effects. In doing so, it considers the biological basis for guiding optimal drug selection. Full article

Background: While anticoagulant and antiplatelet therapies are commonly combined in clinical settings, this combination increases the risk of hemorrhage. However, comparative data on the bleeding risks of different drug combinations remain limited. This study assesses hemorrhage risk associated with various anticoagulant–antiplatelet combinations using data from the USFDA Adverse Event Reporting System (AERS). Methods: Hemorrhage-related reports were extracted from the AERS database (March 2004–June 2024). Anticoagulants analyzed included warfarin, rivaroxaban, dabigatran, apixaban, edoxaban, betrixaban, and acenocoumarol; antiplatelets included aspirin, clopidogrel, ticagrelor, cilostazol, prasugrel, and dipyridamole. Disproportionality analysis using frequentist and Bayesian approaches was conducted to detect hemorrhage signals. Results: Out of 160,715 hemorrhage reports, rivaroxaban, warfarin, and apixaban were the most frequently reported anticoagulants, while aspirin and clopidogrel were the top antiplatelets. Apixaban had the lowest reporting odds ratio for hemorrhage. The rivaroxaban-aspirin combination showed the highest hemorrhage risk, while combinations with cilostazol were the lowest. Apixaban, alone and in combination, was associated with reduced hemorrhage and mortality risks. Conclusions: Combining anticoagulants with antiplatelets increases hemorrhage and mortality risk. While our findings highlight potential safety signals related to hemorrhage with antithrombotic drug combinations, they remain hypothesis-generating and should not be interpreted as causal associations. Instead, they provide an initial basis for further validation in well-designed clinical cohorts where comorbidities can be adequately accounted for. Full article

Background: This study aimed to evaluate the risk of upper gastrointestinal (UGI) adverse events (AEs) associated with oral anticoagulants (OACs) and identify potential interactions with cardiovascular (CV) drugs. Methods: Individual case safety reports (ICSRs) from the FDA Adverse Event Reporting System from July 2014 to December 2023 were analyzed. Dataset I was constructed to assess the associations between OACs and UGI AEs using disproportionality analysis. Dataset Ⅱ included OAC-related ICSRs to explore potential interactions with CV drugs through logistic regression. Positive signals were defined as potential associations identified by disproportionality analysis metrics, such as reporting odds ratios (RORs) or adjusted RORs (aRORs) accounting for confounders. Results: Dataset I included 12,905,290 ICSRs, and a positive signal for dabigatran was detected with an ROR of 1.19 (95% CI, 1.13–1.25). A total of 364,044 OAC-related ICSRs were included in dataset II. At the pharmacologic drug class level, several positive signals were identified, represented as aRORs with 95% CIs: for warfarin, amiodarone analogs (1.22; 1.04–1.43); for apixaban, angiotensin-converting enzyme inhibitors (1.34; 1.24–1.45), angiotensin receptor blockers (1.23; 1.14–1.33), dihydropyridine calcium channel blockers (1.30; 1.21–1.41), and digitalis glycosides (1.72; 1.49–2.00); and for edoxaban, angiotensin receptor blockers (1.88; 1.48–2.37), amiodarone analogs (1.73; 1.06–2.85), and anti-platelets (1.56; 1.20–2.03). No signals were observed for rivaroxaban or dabigatran. At the individual drug level, 62 OAC-CV pairs were identified as having potential interactions. Conclusions: Drug-specific interaction profiles should be considered to ensure safe and personalized use of OACs in clinical practice. Full article

Blunt cerebrovascular injury (BCVI) defines a relatively common finding in trauma-injured patients, seen in roughly 2.4% of trauma patients. Unrecognized and untreated complications of BCVI can include stroke and neurological deficits. Increased use of CT angiography has led to a greater incidence of BCVI in traumatic brain injury and polytrauma patients, prompting a greater understanding of treatment options to mitigate morbidity. Antiplatelet medications, including aspirin and P2Y12 inhibitors (e.g., clopidogrel), as well as warfarin, dual oral anticoagulants (DOAC, e.g., dabigatran, rivaroxaban, apixaban, and edoxaban) provide a wide variety of medical treatment options. This article serves as a review of current evidence from 2015 to 2025 regarding best practices involving antiplatelet and anticoagulation use in the treatment of BCVI. Full article

(1) Background: Atrial fibrillation (AF) is the most common arrhythmia and poses a clinical dilemma in the very elderly due to increased thromboembolic and bleeding risks. This study aimed to evaluate clinical outcomes—including thromboembolic events, major bleeding, and all-cause mortality—by age group in elderly East Asian patients with non-valvular AF receiving oral anticoagulants. (2) Methods: This retrospective single-center study included 502 patients aged ≥70 years treated with direct oral anticoagulants (DOACs: dabigatran, rivaroxaban, edoxaban, or apixaban) or warfarin between 2016 and 2024. Patients were stratified into two age groups: 70–79 and ≥80 years. The primary outcomes were ischemic stroke, systemic thromboembolism, and major bleeding. (3) Results: Although patients aged ≥80 years showed a numerically higher incidence of bleeding in both the DOAC and warfarin groups, these differences were not statistically significant after multivariable adjustment (DOAC group: HR 0.832; 95% CI, 0.456–1.518; p = 0.549; warfarin group: HR 3.617; 95% CI, 0.600–21.804; p = 0.161). Ischemic and thromboembolic event rates were also comparable between age groups. (4) Conclusions: Despite a numerically higher bleeding risk in the very elderly, DOACs remained safe and effective when appropriately managed. These findings support individualized anticoagulation decisions based on clinical factors rather than age alone in elderly East Asian patients with AF. Full article

Oral anticoagulants, including warfarin, a vitamin K antagonist, have been used for anticoagulation therapy, but their limitations, such as drug interactions and complex dosing, have prompted the development of direct oral anticoagulants (DOACs) like rivaroxaban, apixaban, dabigatran, and edoxaban. This study reviews the interactions of both warfarin and DOACs, particularly those influenced by cytochrome P450 enzymes and P-glycoprotein. Warfarin is metabolized by various cytochrome P450 isoforms, making it vulnerable to interactions with medications and herbs that modulate these enzymes. In contrast, DOACs, while having fewer interactions, are still affected by strong inducers or inhibitors of cytochrome 3A4 and P-glycoprotein, depending on the specific drug. Some herbs may also interfere with these pathways. Continuous monitoring of these interactions is crucial to ensure the safe use of oral anticoagulants. The findings underscore the importance of identifying and understanding these interactions to improve patient safety and guide appropriate anticoagulant therapy. Full article

Background/Objectives: Atrial fibrillation (AF) is a very common arrhythmia and the main cause of embolic events. Early diagnosis and treatment are crucial to prevent thromboembolic events. Although DOACs are an important advance in AF management, optimization is required. This study aims to evaluate the newly available evidence and experts’ opinions on the clinical care of AF patients and to develop a set of practical recommendations to improve the management of patients with AF. Methods: A questionnaire was developed on the topics of AF diagnosis, stroke prevention, rate and rhythm control, and management of comorbidities, based on the scientific committee’s judgment and a rapid literature review. The level of agreement of the panelists with each statement was evaluated using the Likert 5-point scale. The results of the questionnaire were discussed in a final meeting and practical recommendations were made. Results: Thirty-five Spanish panelists, all experts in AF management, answered the questionnaire. Most of the statements (78%) reached the levels of agreement or unanimity. Discrepancy (9%) and rejection (13%) were also reported. Conclusions: This study underscores the importance of a 12-lead electrocardiogram to diagnose AF, with wearable devices serving as useful tools; catheter ablation as a superior strategy for restoring and maintaining sinus rhythm compared to pharmacotherapy; the importance of comorbidity management to reduce incidence and recurrence of AF; adherence and persistence as critical factors for the efficacy and safety of anticoagulation; and the preference for DOACs, particularly apixaban and edoxaban, for stroke prevention in patients ≥75 years old or with chronic kidney disease. Full article

Background/objectives: In some cases of concomitant use of direct oral anticoagulants (DOAC) and certain anticancer medications, pharmacokinetic interactions are expected; however, clinical data is scarce. This report reviews the recommendations on the use of DOAC concurrently with anticancer drugs according to different clinical decision support systems and sources, with a focus on discrepancies. Methods: We reviewed the recommendations from the American Heart Association (AHA), European Heart Rhythm Association (EHRA), summary of product characteristics (SPC) in FASS (Swedish medicine information portal), the Swedish clinical decision support system Janusmed, and information from the Food and Drug Administration (FDA) on the concomitant use of apixaban, edoxaban, and rivaroxaban (activated factor X (FXa) inhibitors) and 80 anticancer drugs from 11 categories (240 drug pairs). Results: No warnings of expected pharmacokinetic drug interactions between FXa inhibitors and anticancer drugs were found for 155 drug pairs (65%) across all sources. The remaining 35% of drug pairs were flagged as having possible interactions with FXa inhibitors according to at least one source. Discrepancies in the recommendations from the different sources were reported. The reported discrepancies were, for the most part, associated with different assessments of the mechanism and the extent of pharmacokinetic interactions of each anticancer medication. Also, knowledge sources have different approaches to reporting potential interactions, in some cases reporting clinically relevant strictly pharmacokinetic interactions, whereas others include even patient-specific factors. Conclusions: The lack of clinical data and different recommendations can make clinical decisions on the concomitant use of DOAC and anticancer drugs difficult. Our compilation is meant to assist clinicians in making decisions based on the available evidence, even if it is scarce. Full article