Pharmacokinetic studies suggest that specific prostate cancer therapies may alter the metabolism of direct oral anticoagulants (DOACs), leading to elevated risks of thrombosis or bleeding. To assess the risk of thrombosis or bleeding, population-based, retrospective, parallel analyses were conducted in Ontario and Alberta, Canada, among adults patients with prostate cancer who were prescribed a DOAC and a potentially interacting androgen receptor pathway inhibitor (including enzalutamide, apalutamide, or abiraterone) compared with non-DOACs between 2012 and 2023. Analyses were stratified based on a DOAC-inducer cohort (enzalutamide or apalutamide, which might increase the risk of thrombosis) and a DOAC-inhibitor cohort (abiraterone, which might increase the risk of bleeding). Overlap weighted Cox proportional hazard models accounting for 37 covariates were performed independently in each jurisdiction and were pooled using random-effects meta-analysis. In total, 2997 individuals were included (2107 from Ontario and 890 from Alberta). In patients who received enzalutamide or apalutamide, there was no increased risk of all thrombosis in the DOAC groups compared with the non-DOAC groups (pooled hazard ratio, 0.83; 95% confidence interval, 0.36-1.93). In patients who received abiraterone, no significant differences were observed in any bleeding events comparing the DOAC and non-DOAC groups (pooled hazard ratio, 1.16; 95% confidence interval, 0.10-13.99). The results were consistent in multiple sensitivity analyses. The concurrent use of enzalutamide, apalutamide, or abiraterone with DOACs did not contribute to clinically meaningful changes in the risk of thrombosis or bleeding in individuals with prostate cancer.

Atrial Fibrillation (AF) is a condition that is five times more likely to cause a stroke and necessitates anticoagulation medication. In this regard, rivaroxaban, which is a direct oral anticoagulant (DOAC), has emerged as an alternative to vitamin K agonists (VKAs). Nevertheless, its relative safety and effectiveness compared to VKAs were not well-studied. Thus, a systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to identify the safety and effectiveness of rivaroxaban among patients with AF. The study protocol was registered with PROSPERO (CRD420251059453), and large databases, such as PubMed, Embase, and Scopus, were searched since their inception till March 2025. Outcomes of interest were risk of stroke, myocardial infarction (MI), bleeding, and mortality. The pooled risk ratios (RR) of each outcome were computed using the RevMan random effect model with 95% confidence intervals (CI). In total, four RCTs (n = 17,634) were included, out of which 56.4% of participants were taking rivaroxaban and 43.6% were taking VKAs. Rivaroxaban had a significant effect in reducing the risk of hemorrhagic stroke [RR: 0.59 (95% CI 0.37, 0.94), p = 0.03], systemic embolism [RR: 0.36 (95% CI 0.18, 0.71), p = 0.003], fatal [RR: 0.43 (95% CI 0.29, 0.65), p = 0.0] and intracranial bleeding [RR: 0.63 (95% CI 0.46, 0.86), p = 0.004] while also increasing the risk of death from cardiac causes. There were no significant differences between the cohorts as far as ischemic stroke, MI, Heart Failure hospitalization, mortality, and major and minor bleeding outcomes are concerned. Large-scale trials ought to be carried out to test its importance in enhancing major clinical results such as ischemic stroke, death, and major and minor hemorrhage in AF patients.

The safety and efficacy of direct oral anticoagulants (DOACs) in patients with left ventricular assist devices (LVADs) remain uncertain because of limited comparative data with warfarin. Are DOACs a safe and effective alternative to warfarin in patients with durable LVADs? A retrospective cohort study using the TriNetX database was conducted. Adults with LVADs prescribed DOACs or warfarin were included. Propensity score matching (1:1) was performed to balance baseline characteristics. The primary outcome was all-cause mortality. Secondary outcomes included thromboembolic events, major bleeding, and blood transfusion requirements. Among 3726 patients with LVAD, 79 received DOACs and 3647 received warfarin. After matching, 77 patients remained in each group. At 5 years, all-cause mortality was significantly lower in the DOAC group compared to warfarin (13% vs. 30%, P < 0.001). Rates of thromboembolism and major bleeding were similar, while blood transfusion needs were lower in the DOAC group (13% vs. 22.1%). In this multicenter cohort, DOACs were associated with improved long-term survival and comparable safety outcomes relative to warfarin in LVAD patients. These findings suggest DOACs may be a viable alternative, but larger prospective studies are warranted.

Temporal trends in the use of direct oral anticoagulants prior to stroke admission.

Rationale for and design of the REsolution of LEft VENTricular thrombus (RELEVENT) Trial.

Evaluating patient acceptability of clinical pharmacist engagement following clinical decision support.

Inflammatory protein signatures associated with high rivaroxaban exposure.

P0874 Perioperative management of direct oral anticoagulants in urological surgery – The prospective PAUSE-URO trial

Antithrombotic agents are essential for preventing cerebrovascular and cardiovascular diseases; however, bleeding complications remain a major concern, particularly among elderly patients and those receiving combination therapy. We designed the Bleeding with Antithrombotic Therapy 2 (BAT2) Study, a prospective multicenter registry involving hospitals from a clinical research network in Japan, to clarify the risk of bleeding events in patients taking antithrombotic agents for cerebrovascular and cardiovascular diseases in recent clinical settings. This prospective, multicenter, observational study followed bleeding and ischemic events for up to 2 years in patients with cerebrovascular and cardiovascular diseases. The primary outcome was major bleeding, and secondary outcomes included intracranial hemorrhage (ICH). The 5,250 patients enrolled comprised 3,134 (70±11 years old; male, 66.6%; HASBLED ≥3, 32.8%) treated with single antiplatelet therapy (SAPT), 551 (71±11 years; 25.8%; 40.8%, respectively) with dual antiplatelet therapy (DAPT), 870 (75±10 years; 37.1%; 39.8%, respectively) with direct oral anticoagulant (DOAC) alone, 433 (72±12 years; 34.2%; 41.4%, respectively) with warfarin alone, 143 (76±8 years; 16.8%; 42.7%, respectively) with DOAC plus antiplatelet agents (AP); and 119 (73±12 years; 18.5%; 47.5%, respectively) with warfarin plus AP. During follow-up (median, 1.98 years), 93 patients experienced major bleeding and 55 developed ICH. Compared to the SAPT group (37 events, 0.63%/year), the DOAC (18 events, 1.12%/year; adjusted hazard ratio [aHR] 1.94, 95% confidence interval [CI] 1.09-3.46), warfarin (16 events, 2.02%/year; 3.44, 1.90-6.23), and DOAC plus AP groups (6 events, 2.24%/year; 3.07, 1.28-7.35) exhibited significantly higher risks of major bleeding after multivariable adjustment. DAPT (aHR 2.47, 95%CI 1.11-5.48), warfarin (5.38, 2.65-10.92), and DOAC plus AP (3.86, 1.30-11.47) had significantly higher risks of ICH than SAPT. The DAPT (2.28, 95%CI 1.65-3.14), DOAC plus AP (1.96, 1.08-3.56) and warfarin plus AP (2.83, 1.62-4.92) groups showed significantly higher risks of ischemic events compared to the SAPT group. Oral anticoagulant alone and DOAC with antiplatelet therapy were associated with higher risks of major bleeding events than SAPT in long-term follow-up for patients with stroke and cardiovascular disease.Data access statement:The dataset of the BAT2 study is available to the investigators who participated in this study group upon submission of a reasonable study plan. ClinicalTrials.gov (NCT02889653) and the University Hospital Medical Information Network clinical trial registry in Japan (UMIN 000023669).

Anticoagulation is a critical component in the treatment of cardiovascular diseases. Large randomised controlled trials have demonstrated that direct oral anticoagulants (DOACs) are effective and safe for stroke prevention in patients with atrial fibrillation (AF) and treatment or prevention of venous thromboembolism. Nevertheless, for specific cardiac indications and patient characteristics, vitamin K antagonists (VKAs) rather than DOACs are either preferred, or the benefit of DOACs in comparison to VKAs remains uncertain. These include, among others, mechanical heart valves, AF associated with moderate-to-severe mitral stenosis, left ventricular or atrial thrombus, and older patients with frailty. As VKAs will continue to play a vital role in the management of patients with cardiovascular diseases in the foreseeable future, this review discusses cardiac indications and patient characteristics that necessitate the use of VKAs and general management principles of VKA therapy.

Deep vein thrombosis (DVT) is associated with potentially serious complications such as pulmonary embolism (PE) and postthrombotic syndrome. Superficial vein thrombosis (SVT) is also clinically relevant, as concomitant DVT and/or PE may already be present at initial diagnosis or may develop during follow-up. Which diagnostic and therapeutic steps are most relevant for dermatologists in clinical practice? Overview of the German S2k guideline and selected literature, supplemented by two case vignettes. DVT diagnostics are guided by clinical pretest probability (Wells score). In patients with low probability, anegative D‑dimer test can rule out DVT. In patients with high probability or apositive D‑dimer test, duplex compression ultrasonography is indicated. In confirmed DVT, prompt therapeutic anticoagulation is required, preferably with direct oral anticoagulants, usually for ≥ 3months depending on provocation status and risk of recurrence. In SVT, thrombus length and proximity to the deep venous junction determine management. SVT ≥ 5 cm, marked symptoms, or relevant risk factors warrant 45days of anticoagulation (e.g., fondaparinux 2.5 mgs.c. once daily). SVT < 3 cm from the junction or with progression into the deep venous system requires therapeutic-dose anticoagulation analogous to DVT. Short-segment distal SVT can often be managed symptomatically. Structured risk stratification, focused diagnostic work-up, and guideline-concordant therapy are essential to prevent thromboembolic complications.

Abstract: Non-valvular atrial fibrillation (NVAF) increases the risk of thromboembolic events like stroke. Warfarin has been the standard anticoagulant, but direct oral anticoagulants (DOACs) offer alternatives with fewer monitoring needs. NVAF accounts for a significant portion of ischemic strokes, with estimates suggesting that up to 20-30% of all ischemic strokes are attributable to AF, highlighting the critical need for effective anticoagulation strategies. Warfarin, while effective, is associated with challenges such as narrow therapeutic index, drug interactions, and variability in response due to genetic factors like VKORC1 and CYP2C9 polymorphisms. This systematic review and meta-analysis aims to evaluate the risks of thromboembolic events and bleeding in NVAF patients switching from warfarin to DOACs, synthesizing evidence to guide clinical decisions. The review also explores subgroup variations, long-term implications, and real-world applicability to provide a comprehensive framework for clinicians managing anticoagulation therapy transitions. Following PRISMA guidelines, we searched PubMed, Embase, Scopus, and Cochrane Library up to 2025. Included studies compared outcomes in switching patients. Data were pooled using random-effects models in Review Manager 5.4. We conducted sensitivity analyses to assess the robustness of findings and meta-regression to explore sources of heterogeneity, such as study design and patient demographics. Fifteen studies ( n =120,000) showed slightly reduced thromboembolic risk (RR=0.92, 95% CI: 0.82-1.03, P =0.15, I ²=40%) but reduced major bleeding (RR=0.85, 95% CI: 0.75-0.96, P =0.005, I ²=50%) with DOACs. Subgroup analyses favored apixaban for bleeding reduction ( P -interaction=0.02). Mixed results were noted in frail patients, with some studies showing increased bleeding risk upon switching. Additional analyses revealed that the benefits were more pronounced in patients with CHA 2 DS 2 -VASc (C-Congestive heart failure (1 point)/ H-Hypertension (1 point)/ A2-Age ≥ 75 years (2 points)/ D-Diabetes mellitus (1 point)/ S2-Stroke, TIA, or thromboembolism (2 points)/ V-Vascular disease (prior MI, peripheral artery disease, or aortic plaque) (1 point)/ A-Age 65–74 years (1 point)/ Sc-Sex category (female) (1 point)) scores ≥4, and forest plots demonstrated consistent trends across different DOAC agents. Switching to DOACs generally maintains thromboembolic protection while lowering bleeding risk, supporting their use in select high-risk patients. However, caution is advised in frail or elderly populations where bleeding risks may increase. Future guidelines should incorporate these findings to optimize patient selection and monitoring protocols, potentially integrating pharmacogenomic testing for personalized anticoagulation management.

Intracranial hemorrhage after ischemic stroke in patients on direct oral anticoagulants: results from a prospective observational study.

The efficacy and safety of early direct oral anticoagulant (DOAC) (re)initiation in patients with non-valvular atrial fibrillation (NVAF) after acute onset of intracranial hemorrhage (ICH) are unknown. This study evaluated ischemic and hemorrhagic risks following early DOAC (re)initiation after ICH in patients with NVAF. SAFE-ICH is a multicenter prospective observational single-arm registry study at 32 Japanese hospitals. Eligible patients had NVAF, were aged ≥20 years, and (re)initiated DOAC ≤14 days following symptomatic ICH. Among 240 patients who (re)initiated DOAC (61.3% male; mean [±SD] age 79.4±9.3 years), intraparenchymal hemorrhage predominated (84.6%), followed by subdural (12.9%), intraventricular (1.7%), and epidural (0.8%) hemorrhage. The median (interquartile range) baseline National Institutes of Health Stroke Scale score was 10 (3-16) and time to DOAC (re)initiation was 7 days (5-10 days). Edoxaban, apixaban, and rivaroxaban were used in 55.0%, 35.8%, and 9.2% of patients, respectively. The primary endpoint (composite of symptomatic ICH, any stroke, or death ≤30 days following DOAC [re]initiation) occurred in 12 (5.0%) patients. There were 4 recurrent ICH events (1.7%; all recurrent subdural hemorrhages). Five (2.1%) patients died of non-vascular causes. In Japanese patients with NVAF, early DOAC (re)initiation ≤14 days after ICH appears to have an acceptable risk for ischemic and hemorrhagic events, particularly in patients with intraparenchymal hemorrhage. In patients with subdural hematoma, early DOAC (re)initiation requires vigilant monitoring.

Direct oral anticoagulants (DOACs) are widely used in patients with atrial fibrillation and venous thromboembolism. Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently coprescribed in this population due to comorbid musculoskeletal or inflammatory conditions. However, the combined use of DOACs and NSAIDs is associated with an increased risk of bleeding due to additive pharmacodynamic effects and potential pharmacokinetic interactions. Although the bleeding risk of this drug combination is well-recognized, evidence-based strategies to mitigate such risk remain limited. Current clinical guidelines do not offer detailed, stratified recommendations based on specific NSAID classes, individual DOAC agents, or particular high-risk populations such as elderly patients, individuals with cancer, those with chronic kidney disease, or patients with autoimmune disorders requiring prolonged NSAID therapy. In addition, the clinical relevance of pharmacokinetic interactions involving CYP3A4 and P-glycoprotein (P-gp), which may influence both DOAC and NSAID metabolism, remains insufficiently explored in real-world settings. We conducted a structured literature search across PubMed/MEDLINE, Scopus, and Web of Science from January 2005 to December 2024 using the terms "direct oral anticoagulants," "NSAIDs," "bleeding," "drug interactions," and related MeSH headings. We included pharmacological studies, randomized trials, real-world cohort analyses, narrative reviews, and meta-analyses. Articles were screened by title and abstract, with full-text assessment for eligibility. The concomitant use of NSAIDs and direct oral anticoagulants (DOACs) presents a well-recognized bleeding risk due to their synergistic effects on platelet function and gastrointestinal mucosa integrity. However, the clinical message should not be a blanket prohibition of NSAID use in anticoagulated patients. However, careful and judicious use, at the lowest effective dose and for the shortest necessary duration, should be considered in select clinical situations.

Pancreatic cancer is one of the most thrombogenic malignancies. Venous thromboembolism (VTE) is a frequent and very severe complication. The risk of thrombosis and postoperative hemorrhage, especially post-pancreatectomy, makes thromboprophylaxis difficult to implement in clinical practice depending on what component dominates. A review was conducted using PubMed, Scopus, Web of Science, Elsevier, and Google Scholar databases. Studies published in English focusing on VTE pathophysiology, prevention, and treatment in pancreatic cancer were included. The evidence was summarized descriptively. Two randomized trials (FRAGEM and CONKO-004) have shown that intensified, weight-adjusted low-molecular-weight heparin (LMWH) significantly decreases the incidence of VTE in advanced pancreatic cancer (PC) without significantly increasing major bleeding or enhancing survival rates. Direct oral anticoagulants (DOACs) such as rivaroxaban and apixaban present potential as oral alternatives; however, they are associated with a greater risk of gastrointestinal bleeding. Following pancreatectomy, VTE occurs in 20-25% of patients-frequently after discharge-highlighting the necessity for extended prophylaxis lasting at least 28 days. Minimally invasive surgical techniques are linked to a marginally elevated risk of VTE when compared to open surgery. Nevertheless, the available data concerning dosing, timing, and the resumption of anticoagulation after post-pancreatectomy hemorrhage (PPH) is still inadequate. Current evidence supports the use of LMWH-based anticoagulation strategies for VTE prevention in pancreatic cancer; however, direct evidence for standard prophylactic dosing is lacking, as available randomized trials evaluated intensified regimens. DOACs may be used selectively, considering bleeding risk. The lack of pancreatic-cancer-specific dosing protocols and perioperative guidelines highlights the need for dedicated trials defining optimal anticoagulation strategies and safe timing of therapy after PPH.

Cardiovascular-kidney-metabolic (CKM) syndrome reflects the interplay of cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic risk factors. We examined whether the number, components, and complexity of CKM domains influence outcomes and years of life lost (YLL) in patients with non-valvular atrial fibrillation (AF) receiving direct oral anticoagulants (DOACs). We included 17,378 AF patients (mean age 76.1±10.7 years; 40.9% women) on DOACs from a multicenter Taiwanese database (2012-2021). Patients were followed until outcomes, death, or study end. Overall, 18.2%, 35.0%, 32.2%, and 14.6% of patients had 0, 1, 2, and 3 CKM domains. Women more often exhibited kidney, metabolic, or combined domains. Clinical risks rose stepwise with domain number; patients with 3 domains had the highest risks of ischemic stroke/systemic embolic event/acute coronary syndrome (adjusted hazard ratio (aHR) 1.60, 95% confidence interval (CI) 1.25-2.05), major bleeding (aHR 2.60, 95%CI 2.00-3.38), heart failure hospitalization (aHR 2.83, 95%CI 2.38-3.37), all-cause mortality (aHR 1.80, 95%CI 1.58-2.06), acute kidney injury (aHR 3.42, 95%CI 2.76-4.25), and major adverse renal events (aHR 20.84, 95%CI 14.14-30.71; all p<0.001). Domain-specific analysis showed kidney involvement conferred the strongest risks (except IS/SEE/ACS), while cardiovascular and metabolic domains were more associated with IS/SEE/ACS. YLL rose with more CKM domains, with females associated with greater reductions, especially in cardiovascular (-10.29 vs. -4.67) and metabolic (-4.98 vs. -0.80) domains (p<0.001). Increasing CKM burden was associated with progressively worse prognosis and shorter life expectancy in AF patients on DOACs, with more pronounced impacts in women.

To summarize the clinical experience in emergency surgical treatment of antithrombotic drug-related intracerebral hemorrhage (ATR-ICH) and explore the surgical strategies and key points of perioperative management. A retrospective analysis was conducted on the clinical data of 26 patients with ATR-ICH who underwent emergency surgery in the Department of Neurosurgery of our hospital from January 2023 to December 2024. Targeted coagulation function reversal measures were implemented in all patients preoperatively and intraoperatively. All patients were taking antithrombotic drugs [5 on warfarin, 2 on direct oral anticoagulants (DOACs), 2 on heparin] or antiplatelet drugs (9 on aspirin, 5 on clopidogrel, 3 on aspirin+clopidogrel) when acute intracerebral hemorrhage occurred (including spontaneous intracerebral hemorrhage and posttraumatic intracerebral hemorrhage). Preoperative GCS scores were 6 to 8 in 16 cases and 9 to 12 in 10 cases. The average hematoma volume was 75.6mL. All patients underwent craniotomy for hematoma evacuation, among which 12 cases received decompressive craniectomy. Early postoperative rebleeding (within 72h) occurred in 1 case, and 1 case died. At discharge, GOS scores were as follows: 6 cases of good recovery, 12 cases of moderate disability, 5 cases of severe disability, 2 cases of vegetative state, and 1 case of death. The core of emergency surgery for ATR-ICH lies in rapid and effective reversal of coagulation function, strict grasp of surgical timing, refined surgical operation, and multidisciplinary collaboration during the perioperative period. Data from this group of cases show that standardized comprehensive treatment can significantly reduce the rebleeding rate and improve patient prognosis.

Optimal management of direct oral anticoagulants (DOAC) prior to implantation of cardiac implantable electronic devices (CIED) remains controversial. To determine whether a strategy of minimal interruption of DOAC before cardiac CIED implantation is associated with improved clinical outcomes compared to uninterrupted DOAC use. The electronic clinical records of 310 patients who were on DOAC and underwent CIED implantation were evaluated. The patients were separated into 2 groups: patients in Group 1 had minimal DOAC interruption (DOAC held < 24 h before procedure), while patients in Group 2 continued DOAC before procedure. Resumption of DOAC in both groups was on the same day of the procedure or the next morning at the operator's discretion. Clinically significant pocket hematoma and thromboembolic events were compared. Among the 310 patients, 71 (22.9%) of them had DOAC held < 24 h before procedure, while DOAC was continued without interruption in 239 (77.1%) in the periprocedural period. Clinically significant pocket hematomas were found in 1 patient (1.4%) in the DOAC interrupted group and 24 (10.0%) in the DOAC continuous group (p = 0.046). Low thromboembolic events were observed in both groups: 0 in the minimally interrupted group and 1 (0.4%) in the un-interrupted group (p > 0.05). The bleeding risk in our cohort of patients who underwent CIED implantation with the uninterrupted DOAC approach is higher than previously reported in the literature. A minimally interrupted approach appears to mitigate this risk without significantly increasing the risk of thromboembolism.

Cancer-associated venous thromboembolism (VTE) is one of the most frequent and life-threatening complications in oncology, representing the second leading cause of death in patients with malignancy. Its pathogenesis is multifactorial, driven by tumor-specific procoagulant activity, systemic inflammation, and the prothrombotic effects of anticancer therapies. The risk is particularly high in pancreatic, gastric, cerebral, and pulmonary cancers and is further amplified by advanced disease stage, comorbidities, and treatment-related factors. Management of cancer-associated VTE requires a careful balance between the risks of thrombosis and bleeding. Low-molecular-weight heparins (LMWHs) were long considered the standard of care, based on superior efficacy over vitamin K antagonists. More recently, direct oral anticoagulants (DOACs) have emerged as effective alternatives, offering the convenience of oral administration and comparable efficacy. However, increased rates of gastrointestinal and genitourinary bleeding, drug-drug interactions, and challenges in patients with renal dysfunction or thrombocytopenia complicate their use. Current international guidelines recommend both LMWHs and DOACs as first-line options, with agent selection guided by tumor type, bleeding risk, comorbidities, and patient preference. Despite these advances, unmet needs persist, including recurrent thrombosis despite anticoagulation, management in thrombocytopenic patients, and adherence to prolonged LMWH therapy. Novel strategies, particularly inhibition of coagulation factor XI, hold promise for dissociating antithrombotic efficacy from bleeding risk. Ongoing phase 3 trials of abelacimab may provide critical evidence to refine anticoagulation strategies in patients with complex clinical profiles. Cancer-associated VTE remains a major clinical challenge requiring individualized decision-making and continuous reassessment. Emerging therapies may further improve outcomes in this vulnerable population.