Oral Anticoagulant Prescription Research Articles

Abstract 4118668: Understanding Medication Adherence to Oral Anticoagulants in Atrial Fibrillation Management: Patient and Provider Perspectives in a Mixed Methods Study

Background: Atrial fibrillation (AF) increases risk of stroke. National guidelines recommend oral anticoagulant (OAC) use to reduce this risk. Medication adherence is pivotal for effective AF management, necessitating an understanding of adherence barriers. Aims: This mixed-methods study aimed to identify patient and provider factors influencing OAC adherence. Methods: Patients with nonvalvular AF and OAC prescriptions were sampled from a large community health system serving seven states. A stratified random sample of 2,000 patients was surveyed by mail, achieving a 13.3% response rate (266 patients). Twenty-eight semi-structured interviews were conducted with a purposive sample of patient survey respondents. Eligible providers were surveyed by email, resulting in a 3% response rate (78 providers). Survey data were analyzed descriptively and using multivariable regression models. Interview data were analyzed thematically. Results: Of 213 patients with an adherence score available, 31.5% reported non-adherence. Nonadherent patients were more likely to report poor healthcare experiences, including discrimination in a healthcare setting and poorer mental/emotional health. Receiving information from providers was significantly associated with adherence, especially among younger patients and those with fewer chronic conditions. High self-efficacy score was associated with adherence, particularly among older and rural patients. Interview analyses showed provider communication about AF medications, perceptions of AF as a serious illness, and a sense that medication was helping manage AF were all important for medication adherence. In contrast, most providers (87%) perceived high non-adherence among AF patients, citing forgetfulness, cost, and side effects as the main reasons. Providers’ responses indicate a need for improving communication and support for addressing adherence barriers. Conclusion: Most patients reported adherence to their medications, with adherence being associated with positive healthcare experiences and better mental/emotional health. Providers perceived relatively low adherence among their patients but aligned with patients on the need for improved communication and shared decision making. Tools that encourage discussion with patients and open communication between providers and patients are pivotal for optimizing patient care and enhancing medication adherence and treatment outcomes.

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.

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.

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

Temporal trends in initiation of oral anticoagulants and stroke-free survival among elderly and very elderly patients with new onset atrial fibrillation - a 20-year perspective.

Abstract Background Oral anticoagulants (OACs) significantly reduce the risk of ischemic stroke in patients with atrial fibrillation (AF). However, evidence regarding efficacy of OACs are lacking in the very elderly patients. Aim To examine temporal trends in initiation of OACs and five-year stroke-free survival in the very elderly patients with new onset AF over a time span of 20 years. Methods From the Danish nationwide registries, we identified patients ≥ 65 years of age with new onset AF from 1999 to 2018. The index date was defined as the day of AF diagnosis for outpatients and as the day of discharge for inpatients. Patients with a prescription of OAC, history of bleeding events, or history of stroke/transient ischemic attack prior to index were excluded. Patients were divided into two age groups based on their age at index: 1) 65-84 years (elderly); and 2) ≥ 85 years (very elderly). Patients were further divided into four calendar year groups from 1999-2018, based on the year of inclusion. We investigated the initiation of OACs and calculated the absolute five-year probability of stroke-free survival in both age groups. Results We included 167,122 patients with new-onset AF between January 1st, 1999, and December 31st, 2018. Among the patients, 23.1 % were aged 85 years or older, 48 % were male and 80.5 % had a CHA2DS2-VASc score equivalent to 2 or higher for men and 3 or higher for women. Initiation of OACs increased in both age groups after the guideline implementation of DOACs in 2010 (Figure 1). In the elderly age group, the proportion of patients receiving OACs increased from 50% in 2010 to almost 90% in 2018. In the very elderly age group, the proportion increased from 25% in 2010 to almost 90% in 2018. The probability of the five-year stroke-free survival improved by approximately 15% from 1999 to 2018 in the elderly age group, with no significant changes in the very elderly age group. Conclusion The proportion of elderly AF patients receiving OAC has increased markedly in the last 20 years. Even so, stroke-free survival remains the same among the very elderly patients.Five-year stroke-free survival

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

Risk of death, thromboembolic events, and bleeding in elderly patients with Atrial Fibrillation and Clinical Complexity who are not taking oral anticoagulation

Abstract Background Patients with Atrial Fibrillation (AF) often exhibit Clinical Complexity (CC), defined as ≥2 features, i.e. patients aged ≥75 years plus a body mass index (BMI) &amp;lt; 23/kg/m2 and/or bleeding history and/or chronic kidney disease. No data are available about the clinical course of patients with Atrial Fibrillation (AF) and CC who are not taking oral anticoagulation (OAC). Purpose To assess the risk of thrombotic and hemorrhagic events in patients with Atrial Fibrillation (AF) and CC who are not taking OAC. Methods Retrospective study with a health care research network (TriNetX). Based on the ICD-10-CM codes entered between 2011-2022 from 85 health care organizations mainly located in the United States, AF patients ≥75 years with CC were categorized into two groups based on the use of OAC during the last year before the study period. The primary outcomes were the one-year risk of death, major cardiovascular events ([MACE]: heart failure, stroke, and myocardial infarction), and major bleeding (central nervous system, gastrointestinal, internal bleeding, and hypovolemic shock). Secondary outcomes were each component of the primary outcome and catheter ablation. Cox regression analyses were used to calculate hazard ratios (HRs) and 95% CIs following propensity score matching 1:1. Results Overall, we identified 271,402 AF CC patients not on OAC (80.1±6.8 years, 46.5% females) and 87,101 AF CC patients on OAC (79.8±6.5 years, 47.6% females). Before PSM, AF CC patients not on OAC showed no significant differences in cardiovascular and bleeding risk factors but were less treated with pharmacological treatment than AF CC patients on OAC. After PSM, no significant differences were found between the two groups, but AF CC not on OAC were at higher risk of all-cause death (HR 1.54, 95%CI 1.50-1.57), MACE (HR 1.13, 95%CI 1.11-1.16), and major bleeding (HR 1.34, 95%CI 1.31-1.38), when compared to AF CC on OAC. AF CC patients not on OAC were associated with a higher risk of each component of the primary outcome and with a lower use of catheter ablation procedures (HR 0.48, 95%CI 0.43-0.54) (Table 1). The risk of the composite outcomes was the highest in those with all the three CC components. A progressive increase in OAC prescription was observed during the follow-up period, with increasing of NOACs and lower use of warfarin being observed. There was a clear temporal relationship between increasing OAC prescription and incidence of bleeding in CC patients (Figure 1) Conclusions AF CC patients not on OAC have a high risk of all-cause death, thrombotic and hemorrhagic events. Over time, increasing NOAC use was associated with more bleeding in CC patients. New antithrombotic approaches aimed at reducing thrombotic risk without increasing bleeding risk are needed in these patients.Figure 1 OAC new prescriptions

Temporal trends of prescription rates, dosing of non-vitamin K antagonist oral anticoagulants and clinical outcomes in patients with atrial fibrillation

Abstract Background The launch of non-vitamin K antagonist oral anticoagulant (NOAC) has revolutionized the landscape of stroke prevention in atrial fibrillation (AF). We aimed to analyze the temporal trends of prescription rates of oral anticoagulants (OACs), NOAC dosing, clinical outcomes and in patients with AF. Methods This was a retrospective study using the Taiwan National Health Insurance Research Database. During 2011 to 2020, A total of 249,107 patients aged ≥30 years with newly diagnosed AF were identified. We analyzed the 1-year risks of ischemic stroke, intracranial hemorrhage (ICH), and all-cause mortality for overall population and specifically for NOAC users. Results The prescription rate of OAC increased from 22.1% in year 2011 to 57.7% in 2020 (P&amp;lt;0.001) with NOAC accounting for 91.0% of overall OAC prescriptions. Compared to patients with incident AF diagnosed in 2011, there were increasing trends for a greater decrease in the risks of ischemic stroke (adjusted hazard ratios [aHRs] 0.914 in 2012, 0.879 in 2013, 0.925 in 2014, 0.822 in 2015, 0.754 in 2016, 0.763 in 2017, 0.769 in 2018, 0.713 in 2019 and 0.707 in 2020; all P&amp;lt;0.05) and mortality (aHRs 0.903 in 2014, 0.899 in 2015, 0.830 in 2016, 0.808 in 2017, 0.788 in 2018, 0.810 in 2019, 0.788 in 2020; all P&amp;lt;0.05), while the risk of ICH did not change significantly (Figure 1). For NOAC users, the percentages of high-dose NOACs increased from 11.04% in year 2012 to 44.29% in year 2019 to 2020. The increasing trend in the use of high-dose NOACs was temporally associated with a lower risk of ischemic stroke observed for patients receiving NOACs in year 2015 to 2017 (aHR 0.794) and year 2018 to 2020 (aHR 0.688) compared to those in year 2012 to 2014 (Figure 2). Conclusion In this nationwide cohort study, there was an increasing trend of OAC prescription, temporally associated with a decline of the risk of ischemic stroke and mortality. Even among NOACs users, the risk of ischemic stroke declined gradually, partly explained by the increasing prescriptions of high-dose NOACs.

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.

Assessing methods to ascertain persistence and adherence of oral anticoagulants in patients with atrial fibrillation

BackgroundPersistence and adherence to oral anticoagulants (OACs) is crucial for its effectiveness in stroke prevention in atrial fibrillation (AF). We aimed to assess the impact of different ascertainment methods on estimated persistence rates. MethodsWe conducted a retrospective cohort study based on the Medicare claims data (01/01/2013-12/31/2019). We built an incident user cohort of OAC (apixaban, dabigatran, edoxaban, rivaroxaban, and warfarin) prescription filling. We measured OAC medication persistence and adherence using the following approaches: 1) treatment-anniversary based persistence: if there is an active prescription overlapping the 180th and 365th day with vs. without a 15-day buffer period (i.e., overlapping with 165th-195th and 350th-380th day); 2) dispensing-gap-based persistence: if there is OAC discontinuation defined as having gap between prescriptions more than a threshold (e.g., 5 to 60 days) and secondarily, 3) proportion of days covered (PDC) adherence: proportion of days in which patient had filled medication available over the 365-day interval. ResultsWe identified 1,398,692 patients who initiated OACs during the study interval. With the treatment-anniversary based approach, only 51.2 to 65.4% of the patients persisted with the medication for either warfarin or DOACs at 180 days, and the number dropped to 43.4 to 60.7% at one year. Adding a 15-day buffer period increased the treatment-anniversary based persistence rates by 6.5 to 10.5%. When the allowable gap increased from 5 to 60 days, the persistence rates increased by 36.3 to 42.4% for all OACs. Apixaban users had the highest PDC (74 to 75%) over the 365 days, compared to other OACs (60 to 69%). ConclusionsWe found that the estimated persistence rates are sensitive to the choice of ascertainment methods. When reporting and comparing persistence findings using the claims database, definitions of OAC discontinuation must be clearly delineated.

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.

Ten rules for oral anticoagulants prescription after a stroke

Ten rules for oral anticoagulants prescription after a stroke

Post-discharge pharmacotherapy in people with atrial fibrillation hospitalised for acute myocardial infarction: an Australian cohort study 2018-2022.

Dual antiplatelet therapy with P2Y12 inhibitors (P2Y12i) and aspirin following acute myocardial infarction (AMI) prevents future ischaemic events. People with atrial fibrillation (AF) also require oral anticoagulants (OAC), increasing bleeding risk. Guidelines recommend post-discharge prescribing of direct OAC with clopidogrel and discontinuation of P2Y12i after 12 months, but little is known about use in clinical practice. To describe post-discharge use of OACs and P2Y12i in people with AF and a history of OAC use hospitalised for AMI. We identified 1,330 people hospitalised for AMI with a diagnosis of AF and history of OAC use in New South Wales, Australia, July 2018-June 2020. We identified three aspects of post-discharge antithrombotic medicine use with possible safety implications: (1) not being dispensed OACs; (2) dispensing OAC and P2Y12i combinations associated with increased bleeding (involving warfarin, ticagrelor or prasugrel); and (3) P2Y12i use longer than 12 months.After discharge, 74.3% of people were dispensed an OAC, 45.4% were dispensed a P2Y12i, and 35.8% were dispensed both. People with comorbid heart failure or cancer were less likely to receive OACs. Only 11.2% of people dispensed both an OAC and P2Y12i received combinations associated with increased bleeding; this was more common among people with chronic kidney disease or prior warfarin or statin use. 44.6% of people dispensed both medicines continued P2Y12i for over 12 months; this was more common in people who received a revascularisation or lived in areas of social disadvantage. We identified potential gaps in pharmacotherapy, including underuse of recommended therapies at discharge, use of combinations associated with increased bleeding, and P2Y12i use beyond 12 months. Prescribing vigilance across both hospital and community care is required.

Presentation, care, coronary intervention and outcomes of patients with NSTEMI according to age: insights from the international prospective ACVC-EAPCI EORP NSTEMI registry.

Older people less frequently receive invasive coronary angiography (ICA) for NSTEMI than younger patients. We describe care, ICA data, and in-hospital and 30-day outcomes of NSTEMI by age in a contemporary and geographically diverse cohort. Prospective cohort study including 2947 patients with NSTEMI from 287 centres in 59 countries, stratified by age (≥75years, n = 761). Quality of care was evaluated based on 12 guideline-recommended care interventions, and data collected on ICA. Outcomes included in hospital acute heart failure, cardiogenic shock, repeat myocardial infarction, stroke/transient ischaemic attack, BARC Type ≥3 bleeding and death, as well as 30-day mortality. Patients aged ≥75years, compared with younger patients, at presentation had a higher prevalence of comorbidities and oral anticoagulation prescription (22.4% vs 7.6%, p< 0.001). Older patients less frequently received ICA than younger patients (78.6% vs 90.6%, p< 0.001) with the recorded reason more often being advanced age, comorbidities or frailty. Of those who underwent ICA, older patients more frequently demonstrated 3-vessel, 4-vessel and/or left main stem coronary artery disease compared to younger patients (49.7% vs 34.1%, p< 0.001) but less frequently received revascularisation (63.6% vs 76.9%, p< 0.001). Older patients experienced higher rates of in-hospital acute heart failure (15.0% vs 8.4%, p< 0.001) and bleeding (2.8% vs 1.3%, p= 0.006), as well as in-hospital and 30-day mortality (3.4% vs 1.3%, p< 0.001; 4.8% vs 1.7%, p< 0.001; respectively), than younger patients. Patients aged ≥75years with NSTEMI, compared with younger patients, less frequently received ICA and guideline-recommended care, and had worse short-term outcomes.

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.

Associations Between Changes in Maximum Daily Atrial Fibrillation Duration, Ischemic Stroke, and Mortality.

Atrial fibrillation (AF) outcomes are strongly associated with continuous measures of AF burden. This study sought to assess the association between changes in maximum daily AF duration (MDAFD) and stroke or mortality in patients with cardiac implantable electronic devices (CIEDs). The Optum deidentified electronic health record data set (2007-2021) was linked with the Medtronic CareLink heart rhythm database. Patients with CIEDs and health care activity recorded in the electronic health record were included, excluding those with oral anticoagulation prescription. MDAFD was assessed 30days post implant (baseline period) and 30days before censoring or an event. HRs for the primary analysis were adjusted for components of CHA2DS2-VASc, baseline MDAFD category, and chronic kidney disease. Of 26,400 patients (age 68 ± 13 years; follow-up 2.6 ± 1.6 years) analyzed, 2,544 (9.6%) had AF during baseline. Increased (vs stable or decreased) MDAFD category in follow-up was associated with a higher adjusted rate of stroke and mortality (HR: 1.80; 95%CI: 1.61-2.01). There was no association between decreased MDAFD in follow-up and the combined endpoint (HR: 0.82; 95%CI: 0.68-1.00). Subgroup analysis by baseline MDAFD category demonstrated that increased MDAFD in follow-up was associated with a greater risk of stroke or mortality among patients with no AF at baseline, and decreased MDAFD in follow-up was associated with a lower risk of stroke or mortality among patients with baseline MDAFD of 1 to<5.5 hours and 5.5 to<23.5 hours. In CIED patients not on oral anticoagulation, increased MDAFD in follow-up was associated with a higher rate of stroke and mortality. These results suggest that AF burden, and associated risk, s not stable over time.

Prescription and switching patterns of direct oral anticoagulants in patients with atrial fibrillation

BackgroundThe patterns of direct oral anticoagulant (DOAC) selection and switching to a different oral anticoagulant (OAC) in patients with atrial fibrillation (AF) are unknown. ObjectivesTo describe temporal patterns in first DOAC prescriptions, estimate the incidence, and identify predictors of switching to a different OAC within 1 year in OAC-naive AF patients. MethodsIn this retrospective cohort study, using a near-nationwide prescription registry (IQVIA, the Netherlands), we determined the number of patients per month initiated on each DOAC and identified predictors of switching within 1 year with robust Poisson regression. ResultsWe included 94,874 patients. From November 2015 to November 2019, the monthly use of apixaban (n = 366 to n = 1066, +191%), rivaroxaban (n = 379 to n = 868, +129%), and edoxaban (n = 2 to n = 305, +15,150%) increased, whereas that of dabigatran decreased (n = 317 to n = 179, −44%). In the 66,090 patients with ≥1 year of available calendar time, 7% switched to a different OAC within 1 year. Strong predictors of switching to a different DOAC were using dabigatran (adjusted risk ratio [aRR], 3.33; 95% CI, 3.02-3.66) or edoxaban (aRR, 1.56; 95% CI, 1.34-1.82) rather than apixaban and using a standard DOAC dose (aRR, 2.54; 95% CI, 2.23-2.88). Strong predictors of switching to a vitamin K antagonist were using rivaroxaban (aRR, 1.36; 95% CI, 1.19-1.54 vs apixaban) and using a standard DOAC dose (aRR, 1.49; 95% CI, 1.26-1.77). ConclusionIn the Netherlands, factor Xa inhibitors are increasingly being selected for OAC-naive AF patients. Seven percent of patients switch to a different OAC within 1 year, and the initial DOAC type and dose are strong predictors of switching.

Atrial fibrillation fact sheet in Korea 2024: part 2—stroke prevention in Korean patients with atrial fibrillation

ObjectiveAtrial fibrillation (AF) increases the risk of thromboembolic events, making oral anticoagulants (OACs) essential for high-risk patients. This fact sheet provides nationwide statistics on AF management for stroke prevention in Korea. We aimed to evaluate current anticoagulation treatment trends and strategies in Korea.MethodThe Korean national health claims database from the National Health Insurance Service was used. AF patients aged ≥ 18 years from 2013 to 2022 were included. OAC use, including warfarin and non-vitamin K antagonist OACs (NOACs), was tracked through prescription data. The rates of OAC use were calculated based on continued use, considering prescription dates and amounts. For patients with multiple encounters, the last encounter was used for analysis.ResultsDuring the study, 20.4% of strokes were accompanied by AF, with AF diagnosed within 6 months before or after the stroke. The number of patients diagnosed with AF after a stroke increased from 4893 in 2013 to 6978 in 2022. Among newly diagnosed AF patients requiring OACs, 51% were not prescribed OACs within 6 months. OAC treatment rates for high-risk AF patients increased from 44.6% in 2013 to 77.5% in 2022, with NOAC prescriptions rising significantly after 2015. Regional variations in OAC prescription rates were observed, with lower rates in suburban/rural areas than in urban regions (76.0% vs. 79.6%, p < 0.001).ConclusionsConsiderable strokes could have been prevented with earlier AF detection and OAC treatment through more intensive electrocardiogram screening.