Background: Critically ill adults are more commonly being admitted to intensive care units (ICU) with a recent history of direct oral anticoagulant (DOAC) use. No consensus guidance exists on optimal anticoagulation strategies in critically ill adults with non-valvular atrial fibrillation (NVAF) on DOAC's prior to ICU admission, and there is considerable variability in clinical practice. Objective: To evaluate rates of major bleeding and thrombosis between 2 anticoagulation strategies for NVAF upon ICU admission: package insert (continuation of oral or parenteral anticoagulation per manufacturer recommendations) vs non-package insert (prophylactic dosing or delayed therapeutic anticoagulation). Study design: This was a retrospective cohort study conducted from January 2019 to August 2023. Patients with NVAF and objective evidence of DOAC exposure within 48 hours of ICU admission were included. Those admitted to the ICU for a bleeding event or who received anticoagulation for indications other than NVAF were excluded. Results: A total of 353 patients met inclusion criteria (122 vs 231 in the package insert and non-package insert groups, respectively). There was no significant difference in the composite incidence of major bleeding and stroke or systemic embolism between groups (4.1% in package insert vs 6.1% in non-package insert; P = 0.437). Conclusion: This study demonstrated no difference in the incidence of major bleeding, in-hospital stroke, or systemic embolism with a package insert vs a non-package insert approach to anticoagulation in critically ill patients receiving DOAC therapy for atrial fibrillation. However, more studies are needed to develop evidence-based guidance on anticoagulation management in this population.

Despite the use of direct oral anticoagulants (DOACs), acute ischemic stroke can occur for several reasons. According to international data, 20% of patients with acute ischemic stroke take DOACs, but no comprehensive analysis of this occurrence has been available in Hungary to date. Our aim was to determine the prevalence of DOAC users in Hungarian ischemic stroke patients. We used retrospective analysis of the Semmelweis University stroke registry to evaluate DOAC use in patients with acute ischemic stroke treated consecutively between October 2020 and September 2024. Among the 2918 consecutive patients with acute ischemic stroke within 24 hours, 320 were taking DOAC (10,57%), of these, 276 (86,25%) had a history of atrial fibrillation. 183 patients (57%) were treated with apixaban, 72 (23%) with rivaroxaban, 38 (12%) with dabigatran, and 27 (8%) with edoxaban. Regarding thrombolysis time windows, 173 out of 1379 (12.54%) patients within the standard intravenous thrombolysis window (0-4.5 h) and 63 out of 656 (9.6%) patients within the extended thrombolysis window (4.5-9 h) were receiving DOAC treatment. Among acute ischemic stroke patients taking DOACs, the proportion of women was higher (56.7%), and the average age for was significantly greater (76 years) compared to the overall acute ischemic population (70 years). The 10.57% prevalence of DOAC use among acute ischemic stroke patients was significantly lower than the 20% observed in international data. This discrepancy may be attributable to the later introduction of DOACs in Hungary, differing reimbursement policies, and high drug costs. Further studies are needed to explore the factors explaining this difference and their impact on stroke prevention. The rate of DOAC use among Hungarian acute ischemic stroke patients was below the international average, which warrants targeted studies to optimize anticoagulation strategies. Orv Hetil. 2026; 167(20): 779-783.

The safety of direct oral anticoagulants use during lactation: A systematic review.

Background Cirrhosis results in complex modifications of the hemostatic system, creating both an increased risk of thrombosis and a propensity for bleeding. Historically, anticoagulation in patients with liver disease has relied on vitamin K antagonists (VKAs) and low-molecular-weight heparins (LMWHs). More recently, direct oral anticoagulants (DOACs) have been introduced into treatment guidelines for venous thromboembolism (VTE), supported by findings from large phase III clinical trials. However, these trials have mostly excluded individuals with significant liver disease; thus, management of cirrhotic patients with VTE and atrial fibrillation (AF) is informed primarily by retrospective and real-world studies. Materials and methods To evaluate the safety and efficacy of DOACs in cirrhosis, we conducted a systematic review and meta-analysis. The MEDLINE, Google Scholar, EMBASE, and Cochrane databases were searched for studies comparing DOACs with traditional anticoagulants (VKAs, LMWHs) in patients with cirrhosis. A total of 26 studies comprising 11,258 patients with cirrhosis (predominantly with Child class A and B) were included. Results DOAC use was associated with a significant reduction in thrombotic events (relative risk [RR] 0.72, 95% CI 0.52–0.98) compared to VKAs. Furthermore, DOACs were associated with a significant reduction in major bleeding risk (odds ratio [OR] 0.63, 95% CI 0.47–0.85) Conclusions DOAC appear to offer a favorable treatment option for cirrhotic patients with VTE or AF and compensated Child-Pugh A or B disease, demonstrating an improved balance between efficacy and safety compared to traditional anticoagulants. Given the predominantly observational evidence base, these findings should be considered hypothesis-generating, particularly for patients with decompensated cirrhosis.

Design and rationale of the GUARD-OAC: A randomized controlled trial evaluating proton pump inhibitor cotherapy for gastrointestinal protection in patients requiring direct oral anticoagulants.

Background: Lower limb arterial calcification (LLAC) is a robust imaging biomarker of peripheral artery disease (PAD) severity. Vitamin K antagonists are presumed to accelerate cardiovascular calcification. Direct oral anticoagulants (DOACs) may influence vascular calcification differently, but lower limb data are limited. Methods: We performed a single-center retrospective cross-sectional study comparing LLAC on clinically acquired non-contrast CT between DOAC users and controls without anticoagulation. Patients were propensity score-matched 1:1 (48 DOAC vs. 48 control; n = 96) using baseline clinical covariates. Associations between LLAC scores and perioperative or cardiovascular events were assessed. Segment-specific LLAC was quantified on non-contrast CT and normalized for arterial segment length. A prespecified exposure–duration sensitivity analysis compared the outcomes in patients with ≥5 years of continuous DOAC therapy (n = 22) versus matched controls. Results: In the matched cohort, total LLAC scores did not differ significantly between DOAC and control groups (infrarenal aorta: median 7596.0 vs. 8637.0 (p = 0.487), iliac segment: median 5689.5 vs. 5193.5 (p = 0.602). However, in patients with ≥5 years of DOAC use, LLAC scores were significantly lower in proximal segments: infrarenal aorta median 5593.5 vs. 11,185.0 (p = 0.001997) and iliac arteries 5624.5 vs. 11,501.0 (p = 0.001867)). Higher LLAC was associated with major adverse cardiovascular events (such as myocardial infarction, stroke, or significant bleeding) in controls (p = 0.0023) but not in DOAC-treated patients. Conclusions: In this propensity-matched, cross-sectional CT study, long-term DOAC exposure was associated with lower proximal LLAC scores in a small duration-defined subgroup, while the primary matched analysis showed no overall difference in total LLAC scores. Because baseline (pre-DOAC) imaging was unavailable and residual confounding/survivor bias is possible, these findings should be considered hypothesis-generating and require prospective validation. The cohort reflected a mixed lower-extremity vascular population rather than exclusively classic chronic atherosclerotic PAD, which may limit biological interpretation and generalizability.

Background/Objectives: Atrial fibrillation (AF) is highly prevalent among older adults and is associated with increased thromboembolic risk. Although anticoagulant therapy (AC) is strongly recommended, its use in elderly and multimorbid patients remains suboptimal. This study aimed to describe long-term trends in AC prescribing patterns among hospitalized older patients with AF. Methods: We conducted a retrospective observational analysis using data from the Italian REPOSI registry, including patients aged ≥65 years hospitalized with AF between 2010 and 2023. AC at admission and discharge was analyzed, including vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs), and antiplatelet agents. Temporal trends, admission-to-discharge treatment changes, and patient characteristics associated with therapy modification were assessed descriptively. Results: The study included 2061 AF patients, characterized by multimorbidity and high thromboembolic risk. A marked shift from VKAs to DOACs was observed over time. However, a substantial proportion of cases remained without AC or received only antiplatelet therapy at both admission and discharge, with untreated individuals being generally older and more clinically complex. DOAC use increased steadily but showed a slight decline at discharge after 2020. Clinical variables available in the registry only partially explained AC changes during hospitalization. Conclusions: Despite increasing adoption of DOACs, AC underuse remains frequent among elderly hospitalized patients with AF. These real-world data highlight persistent challenges in AC management in complex older adults and underscore the need for more comprehensive clinical information and data-driven tools to support individualized therapeutic decision-making.

Bleeding is a side effect of direct oral anticoagulants (DOACs) and selective serotonin reuptake inhibitors (SSRIs). However, it is unknown whether their concomitant use would further exacerbate bleeding risk. To compare hazard of bleeding in patients with concomitant use of DOACs and SSRIs versus non-SSRI antidepressants. Population-based cohort and case-crossover study using primary care data from the UK Clinical Practice Research Datalink (CPRD) Aurum between 1/1/2011 and 29/3/2021. We used a cohort design to estimate hazard ratios (HRs) using propensity score weighting, comparing DOAC+SSRI and DOAC+non-SSRI users, and a 6-parameter model case-crossover design comparing odds of exposure to different drug initiation patterns for outcomes in hazard vs referent window within an individual to eliminate time-invariant confounding (confounding that do not change over time). There was no difference in bleeding risk in the cohort design (intracranial bleeding: HR1.16, 99% confidence interval [CI] 0.62-2.20; gastrointestinal bleeding: HR1.09, 99% CI 0.83-1.41; other bleeding: HR1.01, 99% CI 0.78-1.29). In the case-crossover design, we observed higher odds ratio (OR) of 1.64 (99%CI 1.14-2.35) for other bleeding associated with SSRI initiation while taking DOAC than SSRI monotherapy (OR1.06; 99% CI 1.01-1.11; p for Wald test=0.002), but greater odds ratio was not observed in DOAC users initiated non-SSRI (p for Wald test=0.83). We found no evidence of increased risk of intracranial and gastrointestinal bleeding during concomitant use of DOAC+SSRI in the cohort analysis. However, the case-crossover analysis suggested some evidence of a higher risk of other bleeding when initiating SSRIs (but not non-SSRIs) while taking DOACs.

Direct oral anticoagulants vs dual antiplatelet therapy following left atrial appendage closure in atrial fibrillation.

Venous thromboembolism (VTE), encompassing deep vein thrombosis and pulmonary embolism, remains a major global health concern due to its high morbidity and mortality. Over the past decades, significant advances in the understanding of its pathophysiology and management have led to a shift from standardized therapeutic approaches to more individualized strategies. This narrative review aims to analyze contemporary VTE management, focusing on clinical risk stratification, thromboprophylaxis, and the use of direct oral anticoagulants (DOACs). A narrative literature review was conducted using PubMed/MEDLINE, Scopus, Web of Science, and ScienceDirect, including studies published between 2015 and 2026. Clinical trials, systematic reviews, and international guidelines were analyzed to synthesize current evidence. Findings highlight the central role of risk stratification tools, such as the Pulmonary Embolism Severity Index (PESI), in guiding clinical decisions, including outpatient management for low-risk patients. Thromboprophylaxis strategies have evolved with the implementation of validated risk assessment models, particularly in hospitalized populations. The introduction of DOACs represents a major advancement, offering comparable or superior efficacy to vitamin K antagonists, with improved safety profiles and greater convenience. However, their use requires careful consideration in specific populations, including patients with renal impairment, cancer, or pregnancy. Overall, contemporary VTE management reflects a paradigm shift toward personalized medicine, integrating clinical assessment, evidence-based protocols, and patient-centered decision-making. Despite these advances, challenges remain in guideline implementation and treatment individualization. Future research should focus on optimizing long-term outcomes and refining risk stratification models to further enhance clinical care.

DIRECT ORAL ANTICOAGULANTS IN PORTAL VEIN THROMBOSIS IN CIRRHOTIC PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS.

Thrombosis, when considering all its manifestations including myocardial infarction, stroke, and venous thromboembolism, constitutes the leading cause of death world-wide. Treatment of thrombotic diseases has been revolutionized by direct oral anticoagulants (DOACs) targeting thrombin and factor (F)Xa. However, the therapeutic or prophylactic use of DOACs is not without limitations, including persistent and significant bleeding risks. In this review, we summarize and discuss current state-of-the-art of novel and experimental anticoagulation and fibrinolytic/thrombolytic therapies beyond DOACs. In particular, we review studies investigating contact pathway inhibition, including in vitro and in vivo studies of FXIIa and FXIa inhibition, and clinical trials of contact pathway inhibition. We review in vitro and in vivo studies investigating inhibition of common pathway coagulation targets, including FV, FVIII, and FIX. This is followed by analysis of options for the therapeutic targeting of fibrin or fibrinogen and FXIII. Next, we explore opportunities for the therapeutic harnessing of naturally occurring anticoagulant pathways as well as fibrinolytic mechanisms. The current state-of-the-art research for each of these mechanisms is summarized, including whether studies have progressed from in vitro to in vivo experimentation and whether clinical trials have been performed. We highlight particularly novel areas of interest and include evaluation of the relative preclinical and clinical trial progress for the selected targets. The increased understanding of mechanisms driving thrombosis holds promise for future developments in novel anticoagulants that may contribute to reducing the impact and burden of thrombotic diseases while improving safety of current therapeutic options.

Real world experience of direct oral anticoagulant (DOAC) use in Australian children.

Clinical outcomes of direct oral anticoagulants versus warfarin for ischemic stroke caused by left ventricular thrombus: A retrospective one-center study.

ABSTRACTPurposeTo examine oral anticoagulant (OAC) use in older adults residing in long‐term care facilities (LTCFs) since direct OACs (DOACs) were introduced, including trends over time and in people with high‐risk comorbidities (prior gastrointestinal bleed and dementia).MethodsA repeated cross‐sectional study using the Registry of Senior Australians National Historical Cohort was conducted and included individuals aged ≥ 65 years residing in LTCFs in Australia between 2013 and 2019. Yearly age‐ and sex‐adjusted prevalence of OACs and 95% confidence intervals (CIs) were estimated using generalised estimating equation (GEE) Poisson models and adjusted prevalence ratios (aPRs) were calculated to estimate trends.ResultsIn 500 883 individuals, the prevalence of OAC use increased from 12.2% (95% CI 12.1–12.4) in 2013 to 16.5% (95% CI 16.4–16.7) in 2019 [aPR 1.05 (95% CI 1.05–1.05)]. This was driven by an increase in the use of DOACs, from 2.24% (95% CI 2.19–2.29) to 12.5% (95% CI 12.3–12.6) [aPR 1.25 (95% CI 1.25–1.26)]. Increases in OAC use were also observed in people with prior gastrointestinal bleed, from 12.9% (95% CI 11.8–13.9) to 17.1% (95% CI 16.2–17.9) [aPR 1.05 (95% CI 1.03–1.06)]. The use of OACs increased over the study period for people living with dementia from 9.93% to 12.8% [aPR 1.04 (95% CI 1.04–1.05)], and for people without dementia from 15.7% to 21.7% [aPR 1.06 (95% CI 1.06–1.06)].ConclusionsThis population‐based study showed increasing use of OACs among residents of LTCFs, including in higher‐risk comorbidity groups, indicating growing confidence in the use of DOACs in these groups.

Abstract Background Percutaneous coronary intervention (PCI) is a widely used treatment strategy for coronary artery disease. A key challenge in long-term care post-PCI is the optimal antithrombotic regimen. Aim This substudy of the Vienna PCI Registry investigated the long-term effects of direct oral anticoagulant (DOAC) use on major adverse cardiac events (MACE) after PCI in patients with chronic coronary syndrome (CCS), exploring possible pleiotropic properties of DOACs. Methods We analyzed patients from the Vienna PCI Registry treated with a drug-eluting stent (DES) between January 1st, 2015, and December 31st, 2020. The primary endpoint was clinically driven target lesion revascularization (TLR). The secondary composite endpoint (MACE) included TLR, target vessel revascularization (TVR), stent thrombosis (ST), and all-cause death. Results A total of 1,046 CCS patients met inclusion criteria. Among them, 176 patients (16.8%) received triple antithrombotic therapy (TAT) followed by DOAC monotherapy. The primary endpoint TLR occurred significantly less often in TAT patients (2.8% vs 8.4%). MACE rates were similar between TAT and dual antiplatelet therapy (DAPT) patients (17.0% vs 17.0%). All-cause mortality was higher in the TAT group (11.9% vs 7.8%). Multivariable regression showed that TAT followed by DOAC monotherapy was associated with a reduced 5-year risk of TLR compared to patients on DAPT (OR 0.367, 95% CI: 0.147–0.917; p=0.032). Conclusion Patients with triple antiplatelet therapy (TAT) demonstrated a statistically significant risk decrease for the primary endpoint clinically driven TLR in the elective CCS PCI setting at 5-years follow-up, which may be in part due to pleiotropic effects of DOACs.Central IllustrationFor image description, please refer to the figure legend and surrounding text. Cumulative Incidence - TLRFor image description, please refer to the figure legend and surrounding text.

Continuous anticoagulation guided by the CHA2DS2-VASc score is standard for atrial fibrillation (AF) but does not reflect real-time AF occurrence. We evaluated an Apple Watch-guided event-triggered anticoagulation strategy that adjusts direct oral anticoagulant (DOAC) use according to smartwatch detection. This multicenter prospective single-arm study enrolled postablation patients in sinus rhythm who were taking DOACs and had a CHA2DS2-VASc score ≤3. Apple Watch monitoring continued for 360 days. If no AF occurred during Days 1-30, anticoagulation was stopped on Day 31; thereafter, Apple Watch notification or electrocardiogram (ECG) evidence of AF prompted DOAC resumption through Day 360. Of 54 enrolled patients enrolled in the study, 50 comprised the analysis population (mean age 63 years; 10% female; median CHA2DS2-VASc score 2). Across 15,865 person-days, Apple Watch guidance reduced DOAC exposure by 94.6% compared with continuous anticoagulation. Reductions were similar for patients with CHA2DS2-VASc scores of 2-3 and 0-1 (95.0% and 94.0%, respectively; P=0.818). No deaths, strokes, systemic thromboembolic events, or bleeding events were observed. One device malfunction prevented ECG acquisition. In this cohort, Apple Watch-guided event-triggered anticoagulation markedly reduced DOAC exposure without thromboembolic events. Given the limited sample size and low baseline thromboembolic risk, these safety findings should be interpreted cautiously. Results were similar in the prespecified analysis restricted to patients with CHA2DS2-VASc scores of 2-3, the group for whom postablation anticoagulation decisions are most clinically relevant.

The optimal anticoagulation strategy for patients with atrial fibrillation (AF) and obstructive hypertrophic cardiomyopathy (oHCM) remains unclear. This study compared the outcomes of direct oral anticoagulants (DOACs) versus warfarin in this patient population. Data from the TriNetX Research Network were used to identify patients with AF and oHCM treated with either DOACs or warfarin. Patients with a prior history of stroke were excluded. Propensity score matching (PSM) was performed to balance baseline characteristics. The primary outcome was ischemic stroke. Secondary outcomes included: all-cause death, all-cause hospitalization, acute myocardial infarction, gastrointestinal bleed, hematuria, and brain hemorrhage. Hazard ratios (HRs) were estimated by Cox proportional hazard models. A total of 7090 patients in the DOAC group and 3350 in the warfarin group were included prior to PSM. Following PSM, each cohort included 3307 patients. The incidence of ischemic stroke was lower in the DOAC group (3.5%) compared with the warfarin group (4.8%), with a hazard ratio (HR) of 0.74 (95% confidence interval [CI]: 0.58-0.95). All-cause mortality was similar between groups, with 555 (16.8%) deaths in the DOAC group and 575 (17.4%) in the warfarin group (HR: 0.996, 95% CI: 0.89-1.12). All-cause hospitalization rates were lower in the DOAC group (64.5%) compared with the warfarin group (68.7%) (HR: 0.90, 95% CI: 0.85-0.95). No significant differences were observed in the rates of acute myocardial infarction (12.1% versus 12.2%; HR: 1.01, 95% CI: 0.88-1.16), gastrointestinal bleeding (6.9% versus 7.9%; HR: 0.89, 95% CI: 0.74-1.06), hematuria (8.0% versus 8.5%; HR: 0.96, 95% CI: 0.82-1.14), or intracranial hemorrhage (1.5% versus 2.0%; HR: 0.75, 95% CI: 0.52-1.09) between groups. DOACs demonstrated a lower risk of ischemic stroke and all-cause hospitalization rates compared with warfarin in patients with AF and oHCM, supporting the use of DOACs in this patient population.

BackgroundWe aimed to evaluate the impact of concomitant use of oral anticoagulants (OAC) and antiplatelet drugs (APD) on clinical outcomes compared with OAC monotherapy in patients aged ≥75 years with atrial fibrillation.MethodsThe ANAFIE (All Nippon AF [Atrial Fibrillation] in Elderly) Registry was a prospective multicenter observational study in Japan. This subanalysis included patients aged ≥75 years with nonvalvular atrial fibrillation receiving OAC. Patients were classified into OAC monotherapy and concomitant OAC+APD therapy groups. Clinical outcomes, including stroke/systemic embolism, major bleeding, and all‐cause mortality, were compared using Cox proportional hazards models. Within the OAC+APD group, outcomes were also compared between patients using direct OACs and those using warfarin.ResultsAmong 29 818 patients (median age 81 years, 42.3% female), 4861 (16.3%) received OAC+APD therapy. This group had higher proportion of men, previous cerebrovascular disease, and previous myocardial infarction. The group showed increased risk of cardiovascular death [1.57 versus 0.94/100 person‐years, adjusted hazard ratio (aHR), 1.29 [95% CI, 1.01–1.64]. There were no significant differences in stroke/systemic embolism, major bleeding, or all‐cause mortality. Within the OAC+APD group, direct OAC use was associated with lower risks of stroke/systemic embolism (aHR, 0.55 [95% CI, 0.38–0.80]), intracranial hemorrhage (aHR, 0.52 [95% CI, 0.30–0.90]), and all‐cause mortality (aHR, 0.73 [95% CI, 0.58–0.91]) compared with warfarin.ConclusionsIn older patients with atrial fibrillation, OAC+APD therapy was associated with higher incidence of cardiovascular death than OAC monotherapy, without significant differences in other clinical outcomes. For patients requiring combination therapy, DOACs may be preferable to warfarin.

Bariatric surgery (BS) can modulate drug pharmacokinetics. This review sought to provide an overview of the available literature and to establish practical recommendations pertaining to the use of drugs commonly used in dermatology in the post-BS setting. PubMed, EMBASE and Cochrane Library databases were systematically reviewed. This study utilised the PRISMA guidelines and was registered on PROSPERO (ID CRD42024505309). Data collection and risk of bias analysis were conducted in duplicate. This review identified 132 eligible studies. Key inclusion criteria included: primary clinical publication, contains information on the implications of BS on medications used in dermatology and full-text availability. Key exclusion criteria included secondary clinical publications, editorials, animal studies and conference abstracts, not providing information on the impact of BS on drugs commonly used in dermatology, articles written in languages other than English and unavailability of the full-text. Oral liquid formulations, crushed tablets, opened capsules or non-oral alternatives may be preferred over solid formulations. Avoidance of enteric-coated and extended-release formulations has been suggested. Dose escalation may be required for highly lipophilic drugs such as acitretin and isotretinoin. Switching to non-oral contraceptive options may be favoured due to reports of reduced efficacy with oral contraception. Avoidance of non-steroidal anti-inflammatory drugs and oral corticosteroids has been recommended due to the risk of gastrointestinal bleeding and marginal ulceration. The use of direct oral anticoagulants may also increase bleeding risk, post-BS. Dose modifications for mycophenolate mofetil may not be required post-laparoscopic sleeve gastrectomy. The bioavailability of oral tyrosine/Janus kinase inhibitors may be decreased; dose escalation may be required in cases of suboptimal treatment response. Consideration of the potential pharmacokinetic effects of BS on drugs used in dermatology is fundamental to ensure optimal patient care. Until more robust data are available, management should be individualised with frequent monitoring of clinical response, laboratory markers and plasma drug levels. Collaboration with a clinical pharmacist is strongly advised.