Anticoagulant Prescription Research Articles

Association of care specialty with anticoagulant prescription and clinical outcomes in newly diagnosed atrial fibrillation: Results from the GARFIELD-AF registry

ObjectiveTo determine whether stroke prevention strategy, comorbidity management, and clinical outcome risks differ across atrial fibrillation (AF) care specialties. MethodsNewly diagnosed non-valvular AF patients enrolled in the international, prospective GARFIELD-AF registry (enrolment: 2010–2016) were analysed. Prescription of oral anticoagulation (OAC) therapy and select comorbidities was assessed by baseline care specialty: cardiology, primary care, or other specialties (internist/neurologist/geriatrician). Associations between care specialty and 2-year clinical outcomes were evaluated using multivariable Cox frailty models to account for within-country homogeneity. ResultsIn 52,011 patients, 34,172 (65.7 %) were diagnosed and initially managed in cardiology care, 7396 (14.2 %) in primary care, and 10,443 (20.1 %) in other specialties. The inter-country care specialty distribution varied considerably. Non-vitamin K OAC (NOAC) therapy among CHA2DS2-VASc ≥2 patients was more common in cardiology care (31.0 %) than primary care (19.8 %) and other specialty care (24.9 %), but comorbidity management was similar across specialties. Compared to cardiology care, primary care was associated with greater non-cardiovascular mortality (1.21 [1.01–1.45]), major bleeding (1.31 [1.05–1.62]), and new/worsening heart failure risk (2.09 [1.69–2.59]). Care in other specialties was associated with greater all-cause (adjusted hazard ratio, 1.19 [95 % CI, 1.09–1.29]), cardiovascular (1.15 [1.01–1.31]), and non-cardiovascular mortality (1.29 [1.13–1.47]), as well as non-haemorrhagic stroke/systemic embolism (1.48 [1.26–1.73]), major bleeding (1.21 [1.02–1.43]), and new/worsening heart failure risk (1.45 [1.21–1.75]) than cardiology care. ConclusionComorbidity management was similar across AF care specialties, but patients outside of cardiology care had fewer NOAC prescriptions and greater risk for most clinical endpoints. Cardiology expertise may have important implications for AF prognosis.Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF: NCT01090362

Factors influencing the use of direct oral anticoagulants among patients with chronic chagas cardiomyopathy

Objective. Chronic Chagas cardiomyopathy (CCC) carries a high risk of embolic events due to structural changes in the left ventricle and frequent conduction disorders. However, there is limited data on anticoagulant prescription patterns and factors influencing the use of direct oral anticoagulants (DOACs) in these patients. This study aims to characterize CCC patients based on the anticoagulant therapy received and identify factors associated with DOACs use. Materials and Methods. A cross-sectional study was conducted at a tertiary-level hospital in Colombia between 2019-2022. Multivariate logistic regression models were used to assess factors associated with anticoagulant therapy and DOACs use. Results. Among 224 CCC patients, 65.7% (n=153) were on anticoagulants, with DOACs being the most prescribed (53%). Notably, 35% of patients at high risk of stroke (CHA2DS2-VASc) were not receiving anticoagulants. Atrial fibrillation (OR 256.08; 95% CI 61.94-1058.72), ventricular aneurysms (OR 4.82; 95% CI 1.54-15.09), and reduced interventricular septal thickness (OR 0.75; 95% CI 0.60-0.92) were associated with anticoagulant use. DOACs were mainly prescribed for patients with atrial fibrillation (OR 13.29; 95% CI 2.47-71.56) and high bleeding risk (HAS-BLED ≥3, OR 11.36; 95% CI 1.15-112.11). Conclusions. A significant proportion of CCC patients were not receiving anticoagulants despite their high risk of stroke and embolic events. The use of anticoagulation was significantly associated with atrial fibrillation, the presence of ventricular aneurysms and reduced interventricular septal thickness. It is crucial to raise awareness among healthcare professionals in endemic areas to improve treatment.

Abstract 4143227: Incidence of Hemorrhagic Stroke in Hypertrophic Cardiomyopathy

Background: Individuals with hypertrophic cardiomyopathy (HCM) have an elevated risk of ischemic stroke, primarily driven by the increased risk of atrial fibrillation (AF) development in this patient population. This risk remains elevated regardless of CHADS2VASC score; thus, anticoagulation is recommended for all HCM patients with AF. Given the known association between anticoagulant medications and hemorrhagic events, there is likely an assumed risk of hemorrhagic stroke in these individuals. Currently, the incidence of hemorrhagic stroke in HCM and its relationship to AF and anticoagulation has not been well-established in the literature. The goal of this study was to establish the presence of and risk factors for hemorrhagic stroke in individuals with HCM. Methods: A retrospective review of all HCM patients ages 18 and older in our institution’s health system was performed from 2019-2023. ICD 10 codes were used to identify individuals with hemorrhagic stroke. Patient charts were reviewed for additional data including demographics, comorbid conditions, anticoagulant prescription, and other inciting factors prior to the hemorrhagic event. Results: The study cohort comprised 343 HCM patients, of which 47.1% were female and 72.7% were Caucasian. Concurrently, 30% (n=103) had a diagnosis of AF. The overall incidence of hemorrhagic stroke was 2.9% (5.8%, n=6 in those with AF vs 1.7%, n=4 in those without AF); furthermore, AF was associated with a non-statistically significant increased risk of hemorrhagic stroke (RR = 3.36, 95% CI 0.97-11.7). Anticoagulant use at the time of hemorrhagic event was observed in 4 individuals (67%) with AF and 1 individual (25%) without AF. Head trauma and falls were frequently observed as precipitating events prior to hospital admission for hemorrhagic stroke, occurring in 83% (n = 5) of patients with AF and 50% (n = 2) of those without AF. Conclusions: While ischemic stroke and anticoagulant use are commonly studied in those with HCM, the incidence of hemorrhagic stroke in this population is not negligible. Risk of hemorrhagic events in HCM appears largely influenced by anticoagulant use, particularly in those with concurrent AF, and by head trauma. Given the known benefits of anticoagulation on ischemic stroke risk in the HCM population, appropriate counseling and careful attention to individual patient factors may be warranted in the administration of anticoagulants.

An evaluation of the impact of the Lambeth PCN pharmacist anticoagulation skills development project

Abstract Background Atrial Fibrillation (AF) is a prevalent heart condition linked to significant morbidity and mortality due to its association with stroke.1 Despite the clear benefits of anticoagulation in reducing stroke risk, its underuse and suboptimal monitoring remain a concern.2 Aim This study aims to evaluate the impact of a pharmacist-led training programme in Lambeth, London, focusing on improving pharmacists' competency and confidence in managing Direct Oral Anticoagulants (DOACs). It assesses if the training met pharmacists' needs, evaluates current monitoring patterns to determine if training was warranted, and identified areas for further training improvement. Methods The study involved 41 GP practices across 9 Primary Care Networks (PCNs) in Lambeth. Practices were eligible based on their involvement in the management of AF patients prescribed DOACs. All pharmacists at these practices who were actively engaged in anticoagulation management and willing to participate in pre- and post-training assessments were invited to take part. Recruitment involved direct communication through practice managers and emails detailing the study’s objectives and benefits. DOAC monitoring data was extracted from patient medication records and subsequently compared to the South East London anticoagulation guidelines3 to establish compliance percentages. A competency assessment was conducted on pharmacists using a pre- and post-training checklist framework devised by the Consultant Anticoagulant Team at Guy’s and St Thomas’ NHS Foundation Trust (GSTT). The Wilcoxon signed-rank test analysed this paired data, with a p < 0.05 set for statistical significance. Additionally, semi-structured interviews were conducted to gather insights on their training experience and perceptions. Transcripts were coded using NVIVO software to identify themes. Ethical approval was obtained from Kingston University London. Results Of the 2,987 AF patients across the 41 GP practices, 87.6% were on DOACs. Prescribing and monitoring trends were consistent across all GPs, with scope to improve compliance across all parameters, such as CHA₂DS₂-VASc score assessment prior to DOAC initiation. The competency assessment, completed by ten pharmacists, showed a significant improvement post-training, with mean scores rising from 3.3 to 4.1 (p< 0.00001). Improvements were seen across all domains, particularly in explaining the rationale for anticoagulation, showing CHA₂DS₂-VASc and HASBLED scores, and discussing modifiable HASBLED factors. Competency in patient communication remained highest, while managing particular cases like reversal procedures and patients with cancer showed lower competency, indicating areas for training improvement. The interviews, conducted with ten pharmacists, revealed three main themes: (1) Confidence and competence in anticoagulant prescribing and optimisation, (2) Evaluation of the training programme's effectiveness, and (3) Professional growth and career development. Pharmacists reported greater confidence in managing DOACs post-training, though challenges remained in patient engagement and collaboration with GPs lacking DOAC knowledge. Discussion / Conclusion The evaluation proved a positive impact on pharmacists' competency and confidence in DOAC management. Suboptimal monitoring practices in Lambeth highlighted the need for this training programme and its crucial role in improving patient outcomes. Limitations include a small interview sample and potential biases in self-reported evaluations. A longitudinal study is recommended to assess long-term impacts. Ongoing training and systematic data collection are essential, and similar training should be extended to other healthcare professionals.

System-Wide, Electronic Health Record-Based Medication Alerts for Appropriate Prescribing of Direct Oral Anticoagulants: Pilot Randomized Controlled Trial.

While direct oral anticoagulants (DOACs) have improved oral anticoagulation management, inappropriate prescribing remains prevalent and leads to adverse drug events. Antithrombotic stewardship programs seek to enhance DOAC prescribing but require scalable and sustainable strategies. We present a pilot, prescriber-level randomized controlled trial to assess the effectiveness of electronic health record (EHR)-based medication alerts in a large health system. The pilot assessed prescriber responses to alerts for initial DOAC prescription errors (apixaban and rivaroxaban). A user-centered, multistage design process informed alert development, emphasizing clear indication, appropriate dosing based on renal function, and drug-drug interactions. Alerts appeared whenever a DOAC was being prescribed in a way that did not follow package label instructions. Clinician responses measured acceptability, accuracy, feasibility, and utilization of the alerts. The study ran from August 1, 2022, through April 30, 2023. Only 1 prescriber requested trial exclusion, demonstrating acceptability. The error rate for false alerts due to incomplete data was 6.6% (16/243). Two scenarios with alert design and/or execution errors occurred but were quickly identified and resolved, underlining the importance of a responsive quality assurance process in EHR-based interventions. Trial feasibility issues related to alert-data capture were identified and resolved. Trial feasibility was also assessed with balanced randomization of prescribers and the inclusion of various alerts across both medications. Assessing utilization, 34.2% (83/243) of the encounters (with 134 prescribers) led to a prescription change. The pilot implementation study demonstrated the acceptability, accuracy, feasibility, and estimates of the utilization of EHR-based medication alerts for DOAC prescriptions and successfully established just-in-time randomization of prescribing clinicians. This pilot study sets the stage for large-scale, randomized implementation evaluations of EHR-based alerts to improve medication safety. ClinicalTrials.gov NCT05351749; https://clinicaltrials.gov/study/NCT05351749.

Delay and Pay? Healthcare Costs Associated with Late Oral Anti-coagulant Prescribing in People with Atrial Fibrillation.

Atrial fibrillation (AF) is associated with increased morbidity and mortality and exerts an increasingly significant burden on global healthcare resources, with its prevalence rising with an ageing population. Despite a substantial thromboembolic risk, particularly in the period immediately following diagnosis, oral anti-coagulation is frequently not initiated or is delayed. The aim of this study was to evaluate healthcare costs in people with AF, comparing those who were commenced on oral anti-coagulation in the immediate period following the index diagnosis date with those in whom initiation was late and those who never started anti-coagulation. This retrospective cost analysis used linked Scottish health data to identify adults newly diagnosed with AF between January 1st 2012 and April 30th 2019 with a baseline CHA2DS2-VASc score of ≥2. This AF population was sub-divided according to timing of the first prescription of oral anti-coagulant (OAC) during a 2-year follow-up period: never started (OAC never initiated), immediate OAC (OAC prescribed within 60 days of incident AF diagnosis), and delayed OAC (OAC prescribed more than 60 days after incident AF diagnosis). A two-part model was developed, adjusted for key covariates, including age, sex, and frailty, to estimate costs for inpatient admissions, outpatient care, prescriptions, and care home admissions, and overall costs. Of an overall AF population of 54,385, 26,805 (49.3%) never commenced OAC, 7654 (14.1%) initiated an OAC late, and 19,926 (36.6%) were prescribed anti-coagulation immediately. The mean adjusted cost for the overall AF population was £7807 per person per year (unadjusted: £8491). Delayed OAC initiation was associated with the greatest adjusted estimated mean annual cost (unadjusted: £13,983; adjusted: £9763), compared to those that never started (unadjusted: £10,433; adjusted: £7981) and those that received an immediate OAC prescription (unadjusted: £3976; adjusted: £6621). Increasing frailty, mortality, and female sex were associated with greater healthcare costs. AF is associated with significant healthcare resource utilisation and costs, particularly in the context of delayed or non-initiation of anti-coagulation. Indeed, there exists substantial opportunity to improve the utilisation and prompt initiation in people newly diagnosed with AF in Scotland. Interventions to mitigate against the growing economic burden of AF should focus on reducing admissions to hospitals and care homes, which are the principal drivers of costs; prescriptions and outpatient appointments account for a relatively small proportion of overall costs for AF.

10-Year Trends of Antithrombotic Therapy Status and Clinical Outcomes in Patients With Atrial Fibrillation and Renal Dysfunction - The Fushimi AF Registry.

Anticoagulation therapy for atrial fibrillation (AF) has undergone major changes following the introduction of direct oral anticoagulants (DOAC) in 2011. However, the transition of anticoagulation therapy for AF patients with severe renal dysfunction remains to be elucidated. Follow-up data, including creatinine clearance (CrCl), were available for 3,706 patients in the Fushimi AF Registry. We divided patients into 3 groups based on CrCl as follows: (1) CrCl ≥50 mL/min; (2) 50 mL/min>CrCl≥30 mL/min; and (3) CrCl <30 mL/min. In patients with CrCl ≥50 mL/min and 50>CrCl≥30 mL/min, prescription of oral anticoagulants increased year-by-year from 2011 to 2021 with a growing proportion of DOAC; however, the prescription of oral anticoagulants remained almost unchanged in those with CrCl <30 mL/min. In patients with CrCl ≥50 mL/min and 50 mL/min>CrCl≥30 mL/min, the incidence of adverse events, including stroke/systemic embolism and major bleeding, was lower among patients enrolled after 2014 than before 2013. However, these trends were not seen in patients with CrCl <30 mL/min. Despite the increased use of DOAC in patients with AF since 2011, anticoagulation therapy for AF patients with severe renal dysfunction has largely remained unchanged, and a reduction in adverse events in those patients has not been observed.

Incidence and outcomes of transient new-onset atrial fibrillation complicating acute coronary syndromes: results from a systematic review and meta-analysis

Abstract Background The overall risk of long-term adverse events of a transient episode of new-onset atrial fibrillation (AF) in patients with acute coronary syndrome (ACS) remains uncertain. This meta-analysis aimed to assess the prognostic impact of transient new-onset AF complicating ACS. Methods and results Cohort studies examining the risk of adverse events in patients with transient new-onset AF compared to those in sinus rhythm after ACS were identified through a comprehensive search of MEDLINE, Scopus, Cochrane, and Google Scholar Library. Studies reporting the incidence of ischaemic stroke events, recurrent AF, or all-cause mortality at the longest follow-up were included. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CI) were synthesized using inverse variance-weighted random-effects meta-analysis. In the seven observational studies included, comprising 151 735 patients, 6 597 (4.3%) experienced transient new-onset AF, which was associated with an increased risk of ischaemic stroke, recurrent AF, or all-cause mortality (HR: 2.24, 95% CI: 1.75–2.85; P &amp;lt; 0.0001; I2 = 30.76%; seven studies). The results remained consistent across each individual endpoint, including ischaemic stroke (HR 2.38, 95% CI: 1.64–3.44; P &amp;lt; 0.01; I2 = 50.2%; five studies), recurrent AF (HR 4.68, 95% CI: 2.07–10.59; P = 0.0002; I2 = 50.2%; four studies), and all-cause mortality (HR 1.36, 95% CI: 1.08–1.71; P = 0.0089; I2 = 53.25%; four studies). Meta-regression analyses revealed a significant increase in these adverse events associated with ST-elevation myocardial infarction (P = 0.001), while there was a tendency for their decrease associated with oral anticoagulant prescription at discharge (P = 0.07). Conclusions The occurrence of transient new-onset AF is associated with an elevated long-term risk of stroke, recurrent AF, and all-cause mortality in patients with ACS. Consequently, these data urge randomized clinical trials to assess the best antithrombotic regimen while potentially helping the current treatment decision-making process for these patients.

Predictors of discordance in estimating the presence of chronic kidney disease among patients with atrial fibrillation and impact on prescription of anticoagulants and cardiovascular outcomes

Abstract Background In patients with atrial fibrillation (AF), the prevalence, predictors and clinical implications of a potential discordance in estimating the presence/absence of chronic kidney disease (CKD) according to Cockroft-Gault (CG) and CKD-EPI formulas remain unclear. Objective To examine patients characterized by discordance in evaluation of renal function, specifically with regard to the threshold for defining the presence of CKD according to an estimated glomerular filtration rate (eGFR) &amp;lt; 60 ml/min, in a large cohort of European AF patients, and to assess the association with prescriptions of oral anticoagulants (OAC) and the risks of adverse outcomes. Methods Data related to AF patients enrolled in a large European observational prospective registry with an average follow up of 645.2 days were analysed. We evaluated renal function for assessing the presence of CKD according to CG and CKD-EPI formulas and we categorized the population in four groups: eGFR ≥ 60 ml/min according both to CG and CKD-EPI (Concordant ≥ 60); &amp;lt; 60 ml/min according to both formulas (Concordant &amp;lt;60); CG &amp;lt;60 ml/min and CKD-EPI ≥60 ml/min (Discordant-CKD-EPI), CG ≥ 60 ml/min and CKD-EPI &amp;lt;60 ml/min (Discordant-CG). Logistic regression analyses were used to assess factors associated with a Discordant assessment of CKD and its association with OAC therapy. Cox regression analysis was used to determine association between categories and the risk of adverse outcome. The primary endpoint was a composite of all-cause death and major adverse cardiovascular events (MACEs). Results 8.786 patients with AF (mean age 68.70, SD 11.58 years; 40.9% female) were included in the analysis. 1360 (15.5%) of them had Discordant CKD assessment: 577 (6.6%) with Discordant-CKD-EPI and 783 (8.9%) with Discordant-CG. Increasing age, female sex and coronary artery disease (CAD) were associated with Discordant-CKD-EPI, while BMI and heart failure (HF) showed an inverse association (Figure 1). Conversely, BMI and HF were factors significantly associated with Discordant-CG. Discordant-CKD-EPI patients showed lower odds of being prescribed with OAC therapy (odds ratio [OR] 0.71, 95% confidence interval [CI] 0.54-0.95) with no significant differences regarding the type of OAC therapy (warfarin or direct oral anticoagulants). At Cox regression analysis, patients with Discordant-CKD-EPI showed a higher risk of composite endpoint events (Figure 2) and both Discordant-CKD-EPI and Discordant-CG patients were associated with a higher risk of all-cause death. Conclusions Age, BMI, female sex and comorbidities associated with AF (CAD and HF) significantly influenced the probability of having a discordant assessment of the presence of CKD, according to estimation of renal function impairment using CG or CKD-EPI formulas, respectively. A discordant assessment of CKD influenced the probability of being prescribed with OAC and was associated with a higher risk of adverse outcomes.Figure 1Figure2

Frailty and anticoagulant prescription in older hospitalized patients with atrial fibrillation: a multi-centred observational study

Abstract Background Evidence of the impact of frailty on anticoagulant prescription in older people with atrial fibrillation (AF) is conflicting. Some studies suggested that oral anticoagulants (OACs) were underutilized in older people with frailty while others have not found this. Aims The primary aim of this study was to examine the prevalence of frailty in hospitalized older patients with AF and the association between frailty and OAC prescription during admission. The secondary aim was to examine the association between frailty and prescription of rate/rhythm control medications during admission. Methods This is a retrospective observational cohort study. Adults aged ≥65 years with AF admitted to six hospitals in Australia between 1 June 2022 and 31 August 2022 were eligible for this study. Frailty was defined by a Frailty Index constructed using information from the electronic medical records. Logistic regression models were applied to examine the association between frailty and the prescriptions of OACs, rate control drugs and rhythm control drugs during admission. Results are presented as odds ratios and 95% confidence intervals. Results A total of 685 patients were included in this analysis. They had a mean age of 82.6, and 49.8% were female. Using the cut-off point of 0.25, 42.8% of the patients were identified as being frail. Overall, 75.6% of the patients were prescribed OACs (67.9% in the frail compared to 81.4% in the non-frail, p&amp;lt;0.001), 37.7% received rate control drugs (42.0% in the frail versus 34.4% in the non-frail, p=0.044), while 27.3% received rhythm control drugs (22.9% in the frail compared to 30.6% in the non-frail, p=0.024). The adjusted odds ratios of frailty on prescriptions during admission were 0.53 (95%CI 0.37 – 0.78) for OACs, 1.45 (95%CI 1.05 – 1.99) for rate control drugs, and 0.79 (95%CI 0.55 – 1.13) for rhythm control drugs. Conclusion Our study found a high prevalence of frailty in older inpatients with AF and frailty was associated with a reduced likelihood of receiving OACs. Further studies are needed to understand the reasons for under-coagulation in frail patients with AF.Prescriptions of OACs during admission

Dynamic recommendation for anticoagulant treatment in patients with atrial fibrillation using deep reinforcement learning method

Abstract Background Recent evidence suggests that the guideline-directed anticoagulant therapy for atrial fibrillation (AF) remains controversial. Widely-used CHA2DS2-VASc score is solely based on limited traditional cardiovascular risk factors, omitting AF characteristics and other markers of thromboembolic risk. A more efficient, safer and more personalized anticoagulant approach is warranted. Purpose To develop a data-driven deep reinforcement learning (DRL) model for guiding dynamic anticoagulant treatment in AF patients to improve cardiovascular outcomes. Methods Participants of this study were enrolled from the multicentred China Atrial Fibrillation (China-AF) Registry between August 2011 and December 2022, who were with regular follow-up every 6 months. We excluded patients on warfarin at baseline due to its declining usage trend in non-valvular AF patients in China. The DRL model was trained in 70% randomly selected patients for optimal dynamic decision-making, and then subsequently tested in the remaining 30%. Data of sociodemographic characteristics, AF characteristics, medical history, lifestyle factors, laboratory examination, and medications were input for model training. Concordance rate between DRL model’s recommendations and physicians’ actual decisions of non-vitamin-K-antagonist oral anticoagulant (NOAC) prescription among all visits before censoring was calculated for each patient. Primary outcome was the composite of cardiovascular death, ischemic stroke, transient ischemic attack or systemic embolism (SSE), and major bleeding. Shapley additive explanation analysis ranked the most important factors affecting decision-making of the DRL model. Results A total of 20068 patients (mean age: 63.0±12.0 years; 36.2% female) were randomly divided into a training cohort of 14050 patients and a testing cohort of 6018 patients. The model’s NOAC recommendations were mostly affected by age, prior NOAC prescription, body mass index, hypertension history and prior statin prescription (Figure 1). Patients with concordance rates of 50.1%-75% and 75.1%-100% had significant risk reductions for the primary outcome (adjusted HR =0.63; 95% CI, 0.46-0.85; P = 0.003 and adjusted HR =0.59; 95% CI, 0.46-0.75; P &amp;lt;0.001, respectively), compared to those with a concordance rate of 0-25%. Similar results were observed for all-cause death, cardiovascular death and SSE outcomes, that patients with the highest concordance rate had a significant lower risk, compared to those with the lowest concordance rate. There was a nonsignificant but similar trend with regard to major bleeding events (Figure 2). Conclusions This modelling study suggests that a data-driven DRL model might provide more efficient, safer and more personalized anticoagulant suggestions, potentially assisting physicians in clinical practice.

Association between warfarin and direct oral anticoagulants users and risk of mortality: cohort studies in England and Hong Kong

Abstract Background The evidence of the association between warfarin and risk of mortality compared with direct oral anticoagulants (DOACs) has been mixed in current literature. Purpose To investigate the association between all-cause mortality and warfarin, compared with DOACs. Methods Population-based cohort studies were conducted using the data from the Hong Kong Clinical Data Analysis and Reporting System (CDARS) and United Kingdom Clinical Practice Research Datalink (CPRD) Aurum. People with atrial fibrillation aged ≥18 years who initiated warfarin or a DOAC during the study period (1st Jan 2014 - 31st Dec 2019) were identified. Follow-up started from the first date of oral anticoagulant prescription and ended at earliest of the date of death, the day before drug switching (between warfarin and DOACs), transferring out of the practice (CPRD Aurum only), last data collection date for the practice (CPRD Aurum only) or the end of study period. We estimated propensity score (PS) based on the list of potential confounders including demographics, co-morbidities, co-medications and polypharmacy. Cox proportional hazards regression model with PS-weighting was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results Among 227,190 new oral anticoagulant users, 54,367 (23.93%) died. The median follow-up was 2.96 and 2.45 years in CPRD and CDARS, respectively. Compared with DOAC use, a lower hazard of all-cause mortality was found in warfarin use (PS-weighted hazard ratio [HR]=0.94, 95% confidence interval [CI]=0.89-0.99) in CPRD; while a higher hazard was observed in warfarin users (PS-weighted HR=1.31, 95% CI=1.24-1.39) in CDARS, versus DOAC users. Consistent results were seen in both databases when stratified warfarin users by Time in Therapeutic Range (TTR). We observed a lower hazard of all-cause mortality in warfarin users with TTR≥65% (PS-weighted HR=0.90, 95% CI=0.85-0.94 in CPRD; 0.87, 0.79-0.96 in CDARS) and increased hazard in warfarin users with TTR&amp;lt;65% (PS-weighted HR=1.37, 95% CI=1.25-1.49 in CPRD; 1.57, 1.48-1.66 in CDARS), versus DOAC users. Conclusions The hazard of all-cause mortality associated with warfarin compared with DOACs were found to be conflicting across databases. However, both databases consistently showed that an increased hazard of all-cause mortality was only found in warfarin users with TTR&amp;lt;65% but not in those with TTR≥65%, suggesting that the differences in hazard of all-cause mortality associated with warfarin compared with DOAC, in part may depend on anticoagulation control in warfarin users. We recommend that warfarin users with poor INR control warrant closer clinical attention and could be considered for a switch to DOACs.

Epidemiology of Deep Venous Thrombosis Among United States Emergency Departments Over an Eight-Year Period.

Deep vein thrombosis (DVT) is a significant cause of morbidity and mortality worldwide, accounting for substantial healthcare utilization. However, as management strategies have evolved, there is a critical need for current data on incidence, admission rates, and medical management of DVT in the ED setting. This cross-sectional study analyzed ED presentations for DVT from 2016-2023 using the Cosmos database. Inclusion criteria comprised patients aged ≥18 years with an ICD-10 code for acute extremity DVT. Outcomes included incidence rates, admission rates, and anticoagulant prescriptions. Data were analyzed using descriptive statistics, and subgroup analyses were performed for upper and lower extremity DVTs. Out of 190,144,463 total ED encounters, DVT represented 368,044 cases (0.2%). Among these cases, 119,986 (32.6%) were admitted, with admission rates stable over the study period. Apixaban was the most prescribed anticoagulant (40.3%), followed by rivaroxaban (28.3%), enoxaparin (7.9%), warfarin (3.6%), and dabigatran (0.3%). Use of apixaban increased from 12.4% in 2016 to 56.2% in 2023. Lower extremity DVTs comprised 88.5% of cases, with a 32.1% admission rate, while upper extremity DVTs accounted for 11.7% of cases, with a 37.0% admission rate. This study provides a summary of DVT presentations and management in United States EDs over an eight52 year period. The findings highlight stable incidence rates, reduced admission rates compared to historical data, and a significant shift towards the use of DOACs, particularly apixaban, for outpatient management. These trends underscore the importance of evidence-based practices 54 and ongoing research to optimize DVT management and improve patient outcomes.

Sex Differences in Prescription Patterns and Medication Adherence to Guideline-directed Medical Therapy Among Patients with Ischemic Stroke.

Background: Ischemic stroke is a leading cause of death and disability. Society guidelines recommend pharmacotherapies for secondary stroke prevention. However, the role of sex differences in prescription and adherence to guideline-directed medical therapies (GDMT) after ischemic stroke remains understudied. The aim of this study was to examine sex differences in prescription and adherence to GDMT at 1-year after ischemic stroke in a cohort of commercially insured patients. Methods: Using the Truven Health MarketScan database from 2016-2020, we identified patients admitted with ischemic stroke. GDMT was defined as any statin, antihypertensive, and anticoagulant prescription within 30-days after discharge. Medication adherence was estimated using the proportion of days covered (PDC) at 1-year. PDC <0.80 was used to define non-adherence. A multivariable model adjusting for covariates was performed to identify the factors associated with non-adherence at 1-year. This analysis was restricted to new users of GDMT. Results: Among 155220 patients admitted with acute ischemic stroke during the study period, 15,919 met the inclusion criteria. The mean age was 55.7 years, and 7,701 (48.3%) were women. Women were less likely prescribed statins (58.0% vs 71.8%), and antihypertensives (27.7% vs 41.8%). In this subset of patients with atrial flutter/fibrillation, women were also less likely prescribed anticoagulants (41.2% vs 45.0%). Women were more likely to be non-adherent (i.e., PDC <0.80) to statins (47.3% vs 41.6%, P<0.0001), antihypertensives (33.3% vs 32.2%, P=0.005), and the combination of both (49.6% vs 45.0%, P=0.003). On multivariable analysis, women were likely to be non-adherent to GDMT at 1-year (odds ratio 1.23, 95% confidence interval 1.08-1.41). Conclusions: In this real-world analysis of commercially insured patients with ischemic stroke, women were less likely initiated on GDMT within 30 days after discharge. Women were more likely to be non-adherent to statins and antihypertensive agents at 1-year. Future efforts and novel interventions are needed to understand the reasons and minimize these disparities.

Brain lesion and echocardiogenic predictors of newly detected atrial fibrillation in acute ischemic stroke

ObjectivesAtrial fibrillation (AF) is one of the notorious risk factors in acute ischemic stroke (AIS), and the use of anticoagulants has been shown to be effective in preventing ischemic stroke in AF patients. Therefore, identifying AF in AIS patients has become increasingly important. However, the impact of brain imaging and cardiac indices on the development of new AF after stroke remains unclear. MethodsA consecutive series of AIS patients who were admitted to the Ulsan University Hospital between January 2013 and December 2019 were identified. Patients with relevant ischemic brain lesions on MRI were included, and those without echocardiography data were excluded. We included and classified the AF patients who had the disease prior to or during hospitalization or met the criteria for cryptogenic stroke (CS). Differences in baseline characteristics, stroke risk factors, stroke severity, insular lesion, and echocardiographic data were investigated among each group. ResultsA total of 850 patients were enrolled in the study, comprising 231 patients with AF detected after stroke (AFDAS), 287 patients with known AF (KAF), and 350 patients with CS. Compared with KAF, patients with AFDAS had a lower prevalence of underlying coronary heart disease and stroke history. They had greater right insular cortex lesions and lesser left atrial enlargement in unadjusted analysis. Following adjusted analysis, the involvement of the right insular cortex was found to be associated with the AFDAS patient group (odds ratio, 1.57). When compared to the CS group, AFDAS patients were older, experienced more severe initial strokes, and had similar rates of pre-stroke anticoagulation prescription. Additionally, they demonstrated a higher prevalence of both insular lesions, increased left atrium volume index, reduced ejection fraction, and elevated e/e′ ratio. After adjustment, age, initial stroke severity, insular involvement, left atrium volume index, ejection fraction, and e/e′ ratio were found to be significant. ConclusionsThese results suggest that the right insular cortex lesion on acute stroke may be a cause of AFDAS.

Time Trends and Excess Mortality Compared to Population Controls after a First-Time Pulmonary Embolism or Deep Vein Thrombosis.

Recent data on temporal trends in excess mortality for patients with pulmonary embolism (PE) and deep vein thrombosis (DVT) compared with the general population are scarce. A nationwide Swedish register study conducted from 2006 to 2018 including 68,960 PE and 70,949 DVT cases matched with population controls. Poisson regression determined relative risk (RR) for 30-day and 1-year mortality trends while Cox regression determined adjusted hazard ratios (aHRs). A significance level of 0.001 was applied. In PE cases, both 30-day mortality (12.5% in 2006 to 7.8% in 2018, RR: 0.95 [95% CI: 0.95-0.96], p < 0.0001) and 1-year mortality (26.5 to 22.1%, RR: 0.98 [0.97-0.98], p < 0.0001) decreased during the study period. Compared with controls, no significant change was seen in 30-day (aHR: 33.08 [95% CI: 25.12-43.55] to 24.64 [95% CI: 18.81-32.27], p = 0.0015 for interaction with calendar year) or 1-year (aHR: 5.85 [95% CI: 5.31-6.45] to 7.07 [95% CI: 6.43-7.78], p = 0.038) excess mortality. The 30-day excess mortality decreased significantly (aHR: 39.93 [95% CI: 28.47-56.00) to 24.63 [95% CI: 17.94-33.83], p = 0.0009) in patients with PE without known cancer before baseline, while the excess 1-year mortality increased (aHR: 3.55 [95% CI: 3.16-3.99] to 5.38 [95% CI: 4.85-5.98], p < 0.0001) in PE cases surviving to fill a prescription of anticoagulation. In DVT cases, 30-day and 1-year mortality declined, while excess mortality compared with controls remained stable. In general, the improved mortality following PE and DVT paralleled population trends. However, PE cases without cancer had decreasing excess 30-day mortality, whereas those surviving to fill a prescription for anticoagulant medication showed increasing excess 1-year mortality.

Epidemiology of pulmonary embolism diagnosis and management among United States emergency departments over an eight-year period

IntroductionPulmonary embolism (PE) is a major cause of morbidity and mortality in the United States. However, as diagnostic imaging, risk stratification tools, and treatment have evolved over time, there is a critical need for current data on the incidence, testing, admission rates, and medical management of PE in the ED setting. MethodsThis was a cross-sectional study of ED patients with PE diagnoses from 1/1/2016 to 12/31/2023 using the Epic Cosmos national database. ED visits were identified using ICD-10 codes corresponding to acute PE. Chronic PEs were excluded. Outcomes included total ED visits, admission rates, anticoagulant treatment prescribed from the ED, and thrombolytic therapy. Anticoagulant prescriptions included warfarin, enoxaparin, dabigatran, apixaban, rivaroxaban, edoxaban, and betrixaban. Thrombolytic agents included alteplase, tenecteplase, and urokinase. We also assessed changes in the overall rate of CT pulmonary angiograms (CTPA) performed. ResultsOut of 186,138,130 total ED encounters, PE represented 531,968 (0.29 %). The overall rate of PE diagnosis rose slowly from 0.20 % in 2016 to a peak of 0.35 % in 2021. Among those with PE, 363,584 (68.3 %) were admitted. The rate of admission declined over time from 75.6 % to 66.1 %. Among those prescribed anticoagulation, the most common medication was apixaban (40.0 %), followed by rivaroxaban (17.3 %), enoxaparin (6.1 %), warfarin (2.6 %), and dabigatran (0.4 %). Thrombolytics were administered in 4.5 % of cases, with the rate of thrombolytics peaking at 5.3 % in 2018 before lowering to 3.5 % in 2023. The overall rate of CTPA increased from 2.4 % to 5.0 %, while the rate of proportion of PEs diagnosed declined from 8.7 % to 6.4 %. ConclusionThis study highlights significant shifts in the epidemiology and management of PE within the ED setting. Overall rates of PE rose, while a larger proportion were discharged. Direct oral anticoagulants have become the predominant therapy with the majority of patients receiving apixaban. Thrombolytic use occurs in a small subset and has been declining over time. CTPA rates have risen, while the overall diagnostic yield has declined.

Gender and contemporary risk of adverse events in atrial fibrillation.

The role of gender in decision-making for oral anticoagulation in patients with atrial fibrillation (AF) remains controversial. The population cohort study used electronic healthcare records of 16 587 749 patients from UK primary care (2005-2020). Primary (composite of all-cause mortality, ischaemic stroke, or arterial thromboembolism) and secondary outcomes were analysed using Cox hazard ratios (HR), adjusted for age, socioeconomic status, and comorbidities. 78 852 patients were included with AF, aged 40-75 years, no prior stroke, and no prescription of oral anticoagulants. 28 590 (36.3%) were women, and 50 262 (63.7%) men. Median age was 65.7 years (interquartile range 58.5-70.9), with women being older and having other differences in comorbidities. During a total follow-up of 431 086 patient-years, women had a lower adjusted primary outcome rate with HR 0.89 vs. men (95% confidence interval [CI] 0.87-0.92; P < .001) and HR 0.87 after censoring for oral anticoagulation (95% CI 0.83-0.91; P < .001). This was driven by lower mortality in women (HR 0.86, 95% CI 0.83-0.89; P < .001). No difference was identified between women and men for the secondary outcomes of ischaemic stroke or arterial thromboembolism (adjusted HR 1.00, 95% CI 0.94-1.07; P = .87), any stroke or any thromboembolism (adjusted HR 1.02, 95% CI 0.96-1.07; P = .58), and incident vascular dementia (adjusted HR 1.13, 95% CI 0.97-1.32; P = .11). Clinical risk scores were only modest predictors of outcomes, with CHA2DS2-VA (ignoring gender) superior to CHA2DS2-VASc for primary outcomes in this population (receiver operating characteristic curve area 0.651 vs. 0.639; P < .001) and no interaction with gender (P = .45). Removal of gender from clinical risk scoring could simplify the approach to which patients with AF should be offered oral anticoagulation.

Venous thromboembolism prevention program implementation in a community oncology practice: a cohort study

While national guidelines recommend Venous Thromboembolism (VTE) risk assessment in cancer outpatients and consideration of pharmacologic prophylaxis in high-risk patients, prophylaxis rates are low in community oncology practices. A successful model for guideline implementation (the Vermont Model, VM) is validated in an academic tertiary oncology setting. We undertook an implementation study to determine the success of this model in a multi-site community oncology practice. The study objectives were to: 1) adapt the VM to the community practice setting; 2) implement the adapted VM into practice; and 3) evaluate clinical and implementation outcomes. The study was carried out in three phases: (1) Pre-implementation, a multidisciplinary team addressed the need to adapt the VM to the local context including electronic medical record (EMR) optimisation and clinician education; (2) implementation of the strategies adapted to the local context, informed by VM and adapted based on stakeholder feedback; (3) prospective evaluation of clinical and implementation outcomes at six months after implementation. Following creation of a comprehensive initiation roadmap for the adaptation of VM program to the community practice, 302 cancer outpatients initiating new treatment met inclusion criteria over a 6 month implementation period. VTE risk education was provided to 100% of patients, and 98% (296) of patients received a VTE risk assessment. Of 52 patients (18%) who scored as high risk based on a modified Khorana (Protecht) score, 14 (27%) initiated prophylaxis. Barriers to program adaptation included EMR optimization challenges and practice-level responsibility assignment, time constraints, concern about potential drug interactions, and financial & insurance issues. Implementation of a multidisciplinary VTE prevention model in the community-based oncology setting successfully increased VTE education and risk assessment rates. AC prophylaxis rates were modestly increased, highlighting the need to understand and address barriers to anticoagulant prophylaxis prescribing in this setting. Northern New England Clinical Oncology Society Research Funding Program.

Surgical Management for Primary Intracerebral Hemorrhage.

The incidence of primary intracerebral hemorrhage (ICH) is increasing, particularly in younger patients, in part, because of increased prescription of anticoagulants. The ICH incidence rate from 2016 to 2018 in the United States was nearly 79 per 100,000 person-years and as high as 367 per 100,000 person-years among those 75 years or older. Worldwide, ICH comprises 28% of all new strokes, but a higher disease burden than ischemic stroke because of its higher morbidity and mortality. While mortality seems to be decreasing, functional outcomes are not improving. After negative trials of open surgical evacuation, recent trials of medical management strategies including intensive blood pressure control and prothrombotic agents intended to reduce hematoma expansion failed to demonstrate efficacy. Concomitantly, continued interest in minimally invasive surgical approaches arose from appreciation of secondary iatrogenic injury incurred to subcortical white matter tracts from open surgical techniques. A positive trial of minimally invasive surgery for lobar hemorrhage has recently been reported, bringing new optimism and demanding a reconsideration of surgical management of ICH. In this narrative review, we summarize the landmark studies, review recent literature, and consider the outstanding questions surrounding surgical management of ICH.