Direct Oral Anticoagulants Dosing Research Articles

Trends of anticoagulant use and outcomes of patients with non-valvular atrial fibrillation: Findings from the RAFFINE registry

BackgroundThe management of non-valvular atrial fibrillation (AF) has evolved with the development of direct oral anticoagulants (DOACs). However, data regarding the effectiveness and safety of DOACs outside clinical trial settings are limited, and off-label dosing of DOACs has not been thoroughly investigated. MethodsWe examined the clinical outcomes of patients with non-valvular AF in the RAFFINE registry, a prospective registry of Japanese patients with AF who were followed-up for more than 3 years. ResultsAmong 3706 patients with non-valvular AF, 42.5% received warfarin and 44.7% received DOACs at baseline. The administration of DOACs increased annually. The mean CHADS2 and HAS-BLED scores were significantly higher in the warfarin group. The unadjusted all-cause mortality, cardiovascular mortality, and incidence of major bleeding events were higher in the warfarin group. The incidence of ischemic stroke/systemic embolism was not different between groups. After adjustment for baseline characteristics, the incidence of these events was not different between groups. Off-label dosing was performed for 32% of patients in the DOAC group, but this did not affect clinical outcomes. ConclusionsThe all-cause mortality, cardiovascular mortality, and incidence of major bleeding events were higher in the warfarin group than in the DOAC group. After adjustment, warfarin use was not associated with an increase in these events. Off-label dosing of DOACs is not rare and is not associated with reduced effectiveness. The impact of off-label dosing of each DOAC on clinical events should be assessed using a larger population.

The Efficacy and Safety of the Off-Label Dose of Direct Oral Anti-Coagulants Treatment in Patients with Atrial Fibrillation in China

Background: Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. Anti-coagulation therapy, especially direct oral anti-coagulants (DOACs) is an indispensable therapy for AF. Considering the increased risks of bleeding, the off-label dose of DOACs has been applied in East Asia. However, the efficacy and safety of off-label dose of DOACs is controversial. Here, we investigate its efficacy and safety in AF patients in China. Methods: This is a retrospective cohort study. Patients diagnosed with AF between January 2015 and December 2015 were recruited. Participants were divided into three groups according to DOACs dose: standard dose of anti-coagulation (SAG) group, off-label dose of DOACs (OFL) group and non-anti-coagulation (NCG) group. Primary endpoint event was all-cause mortality. Secondary endpoint events included thromboembolic events, acute coronary syndrome, major bleeding and any rehospitalization. All endpoints were collected in 2020. Results: 296 patients were included in this study. All-cause mortality in NCG (52%) group was the highest among these three groups (p<0.001), and there was no significant difference between OFL (14%) and SAG group (19%, p=0.601). Compared to SAG group (1.8%), patients in OFL group (16.2%) had higher risk of stroke and thromboembolic events (p<0.001). The incidence of other events including major bleeding (p=0.597) were similar between SAG group (8.1%) and OFL group (5.4%). Conclusions: Off-label dose of DOACs shows no overall benefits in the occurrence of thromboembolic risk compared to the standard dose of DOACs in AF patients in China. Collectively, standard dose of DOACs should be advocated in China.

DOAC dosing: new study suggests pharmacist-led protocol may reduce errors

Studies generally observe that about one-third of all direct oral anticoagulant (DOAC) prescriptions contain at least one dosing error. Could hospital practitioners benefit from pharmacist DOAC dosing consultations? A team of researchers at the University of Maryland Medical Center set out recently to answer this question, publishing the results of a pharmacist-to-dose DOAC pilot study from July of 2021 in the Journal of the American College of Clinical Pharmacy.

Different Renal Function Equations and Dosing of Direct Oral Anticoagulants in Atrial Fibrillation.

Randomized trials of direct oral anticoagulants (DOACs) adopted the Cockcroft-Gault (CG) formula to calculate estimated glomerular filtration rate (eGFR) to determine the dosages of DOACs. The authors aimed to investigate the agreements/disagreements of eGFRs calculated using different equations (CG, Modified Diet in Renal Disease [MDRD], and Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formulas), and their impacts on the dosages of DOACs and clinical outcomes. Medical data from a multicenter health care provider in Taiwan including 39,239 patients with atrial fibrillation were used. Among these patients, there were 11,185 and 2,323 patients treated with DOACs and warfarin, respectively. At the cutoff values of eGFR of<15, 15-50, and >50mL/min, the agreements were 78% between MDRD and CG and 81% between CKD-EPI and CG. The disagreements among the different equations were largely due to overestimations, especially for patients aged >75 years and with a body weight of<50kg (58.8% for MDRD and 50.9% for CKD-EPI). Among patients receiving DOACs whose dosages were defined as "on label" based on MDRD or CKD-EPI, only those whose dosages were "truly on label" based on CG were associated with a lower risk of major bleeding (adjusted HR: 0.34; 95%CI: 0.26-0.45) compared to warfarin. The adoptions of MDRD or CKD-EPI rather than CG would result in inappropriate dosing of DOACs (mainly overdosing), which would attenuate the advantages of DOACs compared to warfarin. The CG equationshould be used as the gold standard to calculate eGFRs and guide the DOAC dosages.

Abstract 104: A Step In The Wrong Direction: The Lack Of Drug Subsidies Drives Patients To Switch From Direct Oral Anticoagulants To Warfarin

Background: Direct oral anticoagulants (DOACs) are superior to warfarin in preventing ischemic stroke from nonvalvular atrial fibrillation (AF). Transitioning from a DOAC to warfarin is rarely medically indicated. The frequency and determinants of switching from DOAC to warfarin, including the potential influence of cost, are not known. Objective: Examine the impact of financial assistance available through Medicaid prescription coverage or low-income subsidy programs on likelihood of switching to warfarin after initiating a DOAC. Methods: We identified patients in the Medicare 5% sample who initiated a DOAC from 2015 to 2017. Patients were eligible if they were age 65 or older, had AF diagnosis, had no oral anticoagulant use during the prior 12 months, and were enrolled in a Medicare Prescription Plan for at least 12 months prior to first oral anticoagulant. Patients who switched to warfarin after an initial DOAC were identified, and their characteristics were evaluated in bivariable and multivariable analyses using Cox regression to adjust for potential confounders and censor for death or end of the observation period. Results: Of 27,151 eligible patients,16,599 (61%), 8,930 (33%), and 1,622 (6%) initiated apixaban, rivaroxaban, and dabigatran, respectively. 30% (8,110) initiated a low dose DOAC. A total of 1,481 (5.5%) switched to warfarin sometime during the follow-up period. The median time to first warfarin dose among patients who switched was 153 days. Overall, 14% of patients were eligible for Medicaid prescription coverage and an additional 8.8% were eligible for other drug subsidies; these patients were significantly less likely to switch to warfarin, compared to other patients (3.4%, 4.1%, 5.8% of patients with Medicaid coverage, other drug subsidies, or neither). After risk adjustment, the relative hazard of switching to warfarin was 0.57 (95% confidence interval (CI): 0.47-0.68) and 0.69 (95% CI: 0.56-0.85), for patients with Medicaid coverage or drug subsidy, respectively, compared to other patients. Conclusions: The financial burden of DOACs may contribute to patients switching to warfarin, despite guideline recommendations. Financial assistance may facilitate evidenced-based best practices in stroke prevention.

Low Exposure to Direct Oral Anticoagulants Is Associated with Ischemic Stroke and Its Severity.

Background and purposeIn acute stroke patients, plasma concentrations of direct oral anticoagulants (DOAC) at hospital admission only poorly mirror DOAC exposure or the coagulation status at the time of the event. Here, we evaluated whether DOAC exposure and DOAC plasma concentration at the time of transient ischemic attacks (TIA) and ischemic strokes correlate with their likelihood of occurrence. Methods Prospectively, consecutive DOAC patients with acute ischemic stroke or TIA were included. Admission DOAC plasma concentrations were measured by ultraperformance liquid chromatography– tandem mass spectrometry. Individual DOAC exposure (area under the curve) and DOAC concentrations at event onset were derived from population pharmacokinetic analyses. Results DOAC exposure was successfully modeled in 211 patients (ischemic stroke 74.4%, TIA 25.6%). Compared to published values, 63.0% had relatively lower DOAC exposure and they more often received lower DOAC doses than recommended (odds ratio [OR], 2.125; 95% confidence interval [CI], 1.039 to 4.560; P=0.044). These patients more likely suffered ischemic strokes than TIA (OR, 2.411; 95% CI, 1.254 to 4.638; P=0.008) and their strokes were more severe (slope, 3.161; 95% CI, 0.741 to 5.58; P=0.011). Low relative DOAC concentrations at event onset were likewise associated with ischemic strokes (OR, 4.123; 95% CI, 1.834 to 9.268; P=0.001), but not to stroke severity (P=0.272). DOAC exposure had a higher explanatory value for stroke severity than concentrations at event. Conclusions Low DOAC exposure is strongly associated to ischemic stroke and its severity. By monitoring DOAC plasma concentrations, patients prone to ischemic stroke might be identified.

Prior direct oral anticoagulant dosage and outcomes in patients with acute ischemic stroke and non-valvular atrial fibrillation: A sub-analysis of PASTA registry study

Background and purposePrescribing under-dose direct oral anticoagulants (DOACs) for non-valvular atrial fibrillation (NVAF) is alerted to increase cardiovascular events or death. However, the association between dose selection of DOACs and the clinical course remains unclear. This study aimed to propose a novel criterion for selecting the DOAC dose and investigate clinical characteristics of ischemic stroke (IS) under this criterion. MethodsWe assessed the pooled prospective multicenter registry data of stroke patients taking anticoagulant agents, including IS patients with NVAF and prior DOAC usage. The recommended dose according to the reduction criteria of each DOAC and the selected dose were identified for each patient, and patients were categorized into four groups: no alternative low-dose, selecting low-dose appropriately with all DOACs applicable for reduction criteria; selected low-dose, selecting low-dose appropriately or inappropriately despite at least one DOAC inapplicable for reduction criteria; selected standard-dose, appropriate standard-dose use; and absolute over-dose, inappropriate standard-dose regardless of criteria. We investigated the effects of dose selection of DOACs on short-term poor functional outcomes. Results322 patients were included in the analysis. The prevalence of no alternative low-dose, selected low-dose, selected standard-dose, and absolute over-dose was 74 (23%), 144 (45%), 89 (27%), and 15 (5%), respectively. Multivariable analysis found that the selected low-dose group showed significantly poorer functional outcomes than the selected standard-dose group only in patients without renal dysfunction (OR, 2.60; 95% CI, 1.17–6.00; P = 0.0186). ConclusionsSelecting a low dose DOAC might be associated with poor functional outcomes in patients without renal dysfunction.

Plasma levels of direct oral anticoagulants in atrial fibrillation patients at the time of embolic stroke: a pilot prospective multicenter study.

Patients with atrial fibrillation (AF) who are on long-term direct oral anticoagulants (DOAC) with low anti-Xa or anti-IIa levels may be at higher risk of recurrent stroke. However, no prospective post-marketing study has investigated these DOAC plasma levels at the time of embolic stroke. The aim of this study was to assess the anti-Xa (rivaroxaban, apixaban) and anti-IIa (dabigatran) plasma levels in DOAC-treated AF patients at the time of acute embolic stroke. We prospectively identified 43 patients with AF on long-term DOAC who experienced embolic strokes. We compared the DOAC plasma levels of these patients with a control sample of 57 patients who tolerated long-term therapeutic dose DOAC therapy without any adverse event. DOAC levels were assessed with drug-specific anti-Xa chromogenic analysis (rivaroxaban, apixaban) and with Hemoclot Thrombin Inhibitor assay (dabigatran). Dabigatran-treated patients with stroke had significantly lower anti-IIa levels when compared with the trough (40.7 ± 36.9 vs. 85.4 ± 57.2ng/mL, p < 0.05) and peak samples of the controls (40.7 ± 36.9 vs. 138.8 ± 78.7ng/mL, p < 0.001). Similarly, there were significantly lower anti-Xa levels in apixaban-treated patients with stroke compared to the trough control samples (72.4 ± 46.7 vs. 119.9 ± 81.7ng/mL, p < 0.05), and in rivaroxaban- and apixaban-treated patients when compared to peak control samples (rivaroxaban: 42.7 ± 31.9 vs. 177.6 ± 38.6ng/mL, p < 0.001; apixaban: 72.4 ± 46.7 vs. 210.9 ± 88.7ng/mL, p < 0.001). This observational study showed significantly lower anti-IIa and anti-Xa plasma levels in AF patients with embolic stroke compared to those who tolerated long-term therapeutic dose DOAC therapy.

Secondary prophylaxis of venous thromboembolism with direct oral anticoagulants: comparison between patients with major congenital thrombophilia versus non-thrombophilic patients.

Direct oral anticoagulants (DOACs) are widely used for the treatment and secondary prophylaxis of venous thromboembolism (VTE). Congenital thrombophilia is a condition that predisposes to a higher incidence of VTE and often requires long-term anticoagulation for secondary prophylaxis. It is less clear the efficacy of DOACs in patients with major thrombophilia. The aim of our study was to evaluate the efficacy and safety of full and reduced DOACs dose for VTE secondary prophylaxis, in patients affected by major congenital thrombophilia compared to a control group of patients with idiopathic recurrent VTE without thrombophilia. We retrospectively evaluated consecutive patients who required long-term anticoagulation for recurrent VTE, treated with DOACs, and compared the outcomes between patients affected by major thrombophilia and the control group. The examined patients were 209. The median time of DOACs therapy was 20months (range 6-90). Two (2.7%) thrombotic events were observed in the subset affected by major congenital thrombophilia (n = 72) and five (3.6%) in the control group (n = 137) (p 0.73). Four (5.5%) hemorrhagic events were reported in the group with major thrombophilia; 21 (15.3%) in the other group (p 0.039). No statistically significant differences were observed in terms of efficacy and safety between DOACs at full and reduced dose. Our data suggest that DOACs may be effective and safe in the secondary VTE prophylaxis in patients affected by major congenital thrombophilia, also at reduced dose.

Direktni oralni antikoagulansi i periferna arterijska bolest

Peripheral arterial disease (PAD) is a disease of the arteries of the lower extremities and represents a global health problem with an increasing prevalence rate. Evidence for the use of standard anticoagulant therapy in patients with PAB is limited. Direct oral anticoagulants are selective inhibitors of activated coagulation factor X and thrombin, thereby blocking the common pathway of the coagulation cascade and preventing fibrin formation. In addition to their procoagulant role, these drugs potentially participate in the regulation of the process of inflammation and tissue fibrosis, which may inhibit the progression of atherosclerotic plaque. The first large study examining the effects of DOAC in patients with atherosclerosis was COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies). This study showed the first encouraging results, although the design was not adapted exclusively to patients with PAD. The VOYAGER PAD (Vascular Outcomes of ASA Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) study laid the groundwork for the use of low doses of direct oral anticoagulants in patients with PAB after revascularization. The applicability of the results of the COMPASS and VOYAGER PAD studies in everyday practice is still questionable. There is clear evidence that the use of direct oral anticoagulants in patients with the peripheral arterial disease may play an important role in the secondary prevention of adverse cardiovascular events, with an acceptable risk of hemorrhagic complications. Additional studies are needed to clarify which groups of patients these drugs have the greatest effect on, in everyday practice.

Prevalence and Risk of Inappropriate Dosing of Direct Oral Anticoagulants in Two Swiss Atrial Fibrillation Registries

Prevalence and Risk of Inappropriate Dosing of Direct Oral Anticoagulants in Two Swiss Atrial Fibrillation Registries

Efficacy and Safety of Direct Oral Anticoagulants in Stable Coronary Artery Disease and Atrial Fibrillation: A Systematic Review and Network Meta-Analysis.

Direct Oral Anticoagulants (DOACs) , which partially replace warfarin, have been developed as a safe and effective therapy for patients with stable coronary artery disease (SCAD) and atrial fibrillation (AF). However, the choice of DOACs and warfarin remains controversial. We conducted a network meta-analysis (NMA) using randomized controlled trials (RCTs) through a systematic literature review to evaluate the the efficacy and safety of DOACs in SCAD and AF patients. Five RCTs with 6524 patients were included. The results showed that patients taking DOACs had a lower risk of stroke/systemic embolism (OR, 0.64; 95% CI, 0.54-0.76, P < .00001, I2 = 89%), intracranial bleeding (OR, 0.41; 95% CI, 0.26-0.64, P = .0001, I2 = 0%), major bleeding (OR, 0.98; 95% CI, 0.81-1.148, P = .80, I2 = 88%), and all-cause mortality (OR, 1.04; 95% CI, 0.88-1.22, P = .66, I2 = 51%) than those taking warfarin. Compared to warfarin, rivaroxaban (20 mg, once/day) was more advantageous in preventing stroke/systemic embolism, as was apixaban (5 mg or 2.5 mg, twice/day) in reducing major bleeding (OR, 0.79; 95% CI, 0.48-1.3) and all-cause mortality (OR, 0.97; 95% CI, 0.69-1.4). Different doses of DOACs showed obvious advantages against intracranial hemorrhage, without significant differences. Thus, DOACs have more effective than warfarin in clinical efficacy and safety.

Off-Label Dose Direct Oral Anticoagulants and Clinical Outcomes in Asian Patients with Atrial Fibrillation: A New Evidence of Asian Dose

Off-Label Dose Direct Oral Anticoagulants and Clinical Outcomes in Asian Patients with Atrial Fibrillation: A New Evidence of Asian Dose

Underdosed Direct Oral Anticoagulants in Atrial Fibrillation Patients Reduce Stroke Severity and Improve Outcome

Background and Purpose: Anticoagulant drugs, including vitamin K antagonist (VKA) and direct oral anticoagulants (DOACs), can reduce stroke severity and are associated with good functional outcomes. Some patients are prescribed lower-than-recommended doses of DOACs; whether these have similar effects has not been clarified. Methods: We retrospectively evaluated 1,139 consecutive ischemic stroke and transient ischemic attack patients with atrial fibrillation. Patients were divided into 5 groups according to their preceding anticoagulant drug therapies: no anticoagulant therapy (AC_n), undercontrolling VKA doses (VKA_uc), recommended, controlling VKA doses (VKA_rec), prescribed underdoses of DOAC (DOAC_ud), and recommended doses of DOAC (DOAC_rec). We investigated the associations between these anticoagulant drug therapies and patients’ initial stroke severity and 3-month outcomes. Results: Median National Institutes of Health Stroke Scale scores at admission were as follows: AC_n: 16, VKA_uc: 15, VKA_rec: 9, DOAC_ud: 5, and DOAC_rec: 7. When the AC_n group was used as a reference, regression analysis showed that VKA_rec (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.01–2.21), DOAC_ud (OR 2.84, 95% CI: 1.47–5.66), and DOAC_rec (OR 1.83, 95% CI: 1.23–2.74) were associated with milder stroke severity, while VKA_uc was not. Median 3-month modified Rankin Scale scores were 2 in the DOAC_ud and DOAC_rec groups and 4 in all other groups. After adjusting for confounding factors, DOAC_ud (OR 3.14, 95% CI: 1.50–6.57) and DOAC_rec (OR 1.67, 95% CI: 1.05–2.64) were associated with good 3-month outcomes while VKA_uc and VKA_rec were not. Conclusions: In patients with atrial fibrillation, recommended doses and underdoses of DOACs reduced stroke severity on admission and were associated with good 3-month outcomes.

Off-label direct oral anticoagulants dosing in atrial fibrillation and venous thromboembolism is associated with higher mortality

Background Direct oral anticoagulants (DOAC) are widely used in our practice. Data on inappropriate DOAC dosing in atrial fibrillation (AF), and venous thromboembolism (VTE) treatment is lacking. Our study aimed to assess the frequency, patterns and clinical outcomes in a racially mixed population. Methods We retrospectively evaluated 1,087 DOAC prescriptions for AF or VTE treatment in six months. Prescriptions were classified as either off-label or appropriate following FDA labeling. The off-label group was subclassified as under or overdosing according to the recommended daily dose. Results Most prescriptions (67%) were for AF. African American and Caucasian patients were equally represented (45% each). There were 171 inappropriate prescriptions (16%), with the majority, 106 (62%), being underdosed. There was a significantly higher 30-day readmissions risk (OR=1.69, 95% CI:1.11-2.54, p=0.012) and 1-year all-cause mortality (OR=1.90, 95% CI:1.02-3.37, p=0.032) in the off-label group. There was no significant difference between major bleeding (OR=1.27, 95% CI:0.63-2.37, p=0.480) or new thromboembolic event (OR=1.27, 95% CI:0.73-2.13, p=0.369) based on dose appropriateness. However, underdosing was associated with higher risk of new thromboembolic events (OR=3.15, 95% CI:1.09-9.15, p=0.024). Conclusions One in every six patients received off-label DOACs dosing. Off-label dosing was associated with increased 30-day readmissions and 1-year all-cause mortality.

Off-Label Under- and Overdosing of Direct Oral Anticoagulants in Patients With Atrial Fibrillation: A Meta-Analysis.

Prescriptions of off-label under- and overdosing of direct oral anticoagulants (DOACs) are common for patients with atrial fibrillation, but their efficacy and safety remain unknown. Databases were searched for randomized controlled trial or adjusted observational study that compared an off-label versus on-label dosing of DOACs through June 15, 2021. The primary efficacy outcome was ischemic stroke/system embolism (IS/SE), and primary safety outcome was major bleeding. Net clinical outcome was generally defined as the composite of IS/SE, major bleeding, and all-cause death. Hazard ratios (HRs) with 95% CIs were pooled with random-effects models with Hartung-Knapp-Sidik-Jonkman method for adjustment. Sixteen studies with 130 609 patients were included. Compared with on-labeling dosing, off-label underdosing of DOACs was associated with a higher risk of IS/SE (HR, 1.22 [95% CI, 1.05-1.42], P=0.01). The incidence of major bleeding was similar (HR, 0.95 [95% CI, 0.82-1.11], P=0.48). Off-label underdosing was associated with a higher risk of net clinical outcome (HR, 1.19 [95% CI, 1.04-1.40], P=0.04) and all-cause death (HR, 1.24 [95% CI, 1.04-1.48], P=0.02). Stratified analysis of off-label underdosing of DOACs for IS/SE showed subgroup differences among different DOAC types and study regions. Limited data showed that off-label overdosing was associated with a higher risk of IS/SE (HR, 1.26 [95% CI, 1.11-1.43], P=0.003) and major bleeding (HR, 1.30 [95% CI, 1.04-1.62], P=0.025). Compared with on-label dosing, off-label underdosing of DOACs increased the risk of thromboembolic events but did not decrease the risk of bleeding. Limited data for off-label overdosing showed higher risks of thromboembolic and bleeding. Further studies are warranted to confirm the results of off-label overdosing DOACs and subgroup results of underdosing DOACs.

Less bleeding associated with apixaban versus other direct acting oral anticoagulation in solid organ transplant recipients.

The purpose of this study was to evaluate outcomes of bleeding and thrombosis resulting from the use of direct oral anticoagulants (DOACs) in a large cohort of solid organ transplant (SOT) recipients. This was a single center, retrospective cohort study of adult kidney, heart, lung, and liver transplant recipients transplanted between August 2009 and May 2018. Patients were stratified into two groups: those who received apixaban (apixaban group) or those patients receiving either rivaroxaban or dabigatran (non-apixaban group). The primary endpoint was the cumulative incidence of bleeding while receiving DOAC therapy. The secondary endpoints were incidence of major bleeding and thrombosis at any time while receiving DOAC therapy. A total of 106 patients were included; 70 patients received apixaban and 36patients received non-apixaban anticoagulation. Cumulative incidence of any bleeding was lower in the apixaban group compared to the non-apixaban group at both 90days (4.9% vs. 16.1%) and 180 days (11.4% vs. 24.9%, P=.034). Cumulative incidence of major bleeding (P=.686) and thrombosis (P=.515) were similar between groups. DOAC dosing congruent with the package insert(s) was associated with a lower risk of thrombosis. Apixaban-based anticoagulation was associated with a lower cumulative incidence of any bleeding compared to non-apixaban DOACs.

Abstract 12248: Dosing of Direct Oral Anticoagulants in Patients With Non-Valvular Atrial Fibrillation and Renal Dysfunction

Introduction: Reduced doses of direct oral anticoagulants (DOACs) are approved to prevent bleeding complications in specified populations of patients with non-valvular atrial fibrillation (NVAF). Little is known about the accuracy of DOAC dosing in patients with renal dysfunction. Hypothesis: We hypothesized that NVAF patients with renal dysfunction would be more likely to receive an inappropriate dose of a DOAC compared with patients with normal renal function. Methods: We examined all patients who had at least two claims for NVAF between 2015 and 2017 in the Symphony Health claims dataset. We defined under-dosing as patients treated with a reduced dose without meeting label specified criteria for dose reduction, and excess dosing as patients treated with a full dose despite meeting criteria for dose reduction. We performed a logistic regression model to measure the effect of CrCl on DOAC dosing. Results: Among 86,919 patients with NVAF and CHA 2 DS 2 -VASc &gt; 2, 12.3% were underdosed and 5.0% were excess dosed. Patients who received excess-dosed or under-dosed DOACs were older and more likely to have comorbidities such as heart failure or history of prior stroke (all p&lt;0.001), compared with patients who were appropriately dosed. Among patients with CrCl &gt; 60 ml/min, under-dosing occurred in 9% of patients, highest among patients treated with edoxaban (18%) and rivaroxaban (10.4%). Under-dosing rates were higher among patients with CrCl 30-59 ml/min, especially for apixaban and dabigatran ( Table) . Excess dosing occurred in approximately 1 in 5 patients with CrCl &lt;30 ml/min. For every 10 unit decrease in CrCl, the odds of the patient receiving an inappropriately dosed DOAC increased by 27%. Conclusions: Incorrect DOAC dosing was observed in a substantial number of patients with NVAF in this large national study. Dosing errors occurred more frequently in patients with lower renal function, suggesting the need for efforts to improve effective and safe dosing of DOACs.

Abstract 11742: Knowledge on Anticoagulation Use in Atrial Fibrillation With Left Atrial Appendage Thrombus Among Medicine Residents

Introduction: Left atrial appendage (LAA) thrombus increases thromboembolic risk in patients with atrial fibrillation (AF). Importantly, 40% of LAA thrombus patients will have an inadequate response to anticoagulation during follow-up. Of note, these patients are frequently followed by medicine residents in the clinic. Therefore, we aimed to explore residents' knowledge on anticoagulation use for the treatment of LAA thrombus. Hypothesis: Insufficient knowledge on anticoagulation for the treatment of LAA thrombus could contribute to inadequate treatment response during patients' follow-up. Methods: All medicine residents (n=96) at Rutgers University New Jersey Medical School were emailed a 26-question survey on the indication, dosing, pharmacokinetics and clinical experience using direct oral anticoagulants (DOACs) and vitamin-K-antagonists (VKA) in AF patients with LAA thrombus. Results: Of 62 responders, 42 (68%) have been prescribing DOACs in the clinic with apixaban being most commonly prescribed. Thirty-seven (61%) indicated DOACs as the first-line agents for LAA thrombus whereas 24 (39%) chose VKA. Nineteen (33%) responders indicated apixaban dosing correctly, and 51 (84%) indicated appropriately relation of apixaban with meals. If follow-up imaging reconfirmed LAA thrombus, 54 (89%) would switch to VKA whereas 7 (11%) would use other DOACs. Nineteen (32%) responders indicated rivaroxaban dosing correctly and only 10 (16%) indicated appropriately how to administer rivaroxaban with meals. If follow-up imaging reconfirmed LAA thrombus, 43 (71%) would switch to VKA whereas 18 (29%) would use other DOACs. Forty-one (72%) responders indicated dabigatran dosing correctly and 36 (58%) indicated no relation to food intake. If follow-up imaging reconfirmed LAA thrombus, 40 (65%) responders would switch to VKA whereas 22 (35%) would use other DOACs. For VKA, 51 (88%) indicated therapeutic INR range of 2-3 and 7 (12%) chose 2.5-3.5. If follow-up imaging reconfirmed LAA thrombus, 38 (61%) would increase INR goal whereas 24 (39%) would switch to DOACs. Conclusions: This survey identified knowledge gaps in dosing and pharmacokinetics of DOACs among medicine residents despite being more likely to prescribe DOACs over VKA to treat LAA thrombus.

Abstract 10113: Improving Safety of Direct Oral Anticoagulant Dosing in Patients with Advanced Chronic and End-Stage Renal Disease

Introduction: Direct oral anticoagulants have become a mainstay in therapy for venous thromboembolism as well as mitigation of stroke and systemic embolism risk in atrial fibrillation. Although guidelines have been put forth for dose reduction in renal impairment, significant inconsistency in dosing practices exists. No study has directly evaluated the dosing practice of apixaban and rivaroxaban in those with advanced chronic kidney disease (stage 4 and 5) and end-stage renal disease at a quaternary care institution. Methods: We screened 853 patients from 1/1/2017 to 3/21/2020 with advanced chronic kidney disease and end-stage renal disease and identified 312 patients on either apixaban or rivaroxaban. Clinical data collected include anticoagulation indication, dosing, serum creatinine, age, weight, and creatinine clearance (calculated by the Cockcroft-Gault equation). Results: A total of 312 patients were studied (268 apixaban, 44 rivaroxaban). Among all patients with advanced chronic kidney disease and end-stage renal disease, a total of 123 patients (46%) were incorrectly dosed with apixaban compared to 17 patients (38%) with rivaroxaban. Among those with advanced chronic kidney disease, 57 patients (41%) were dosed incorrectly with apixaban compared to 10 patients (27%) with rivaroxaban. Among those with end-stage renal disease, 66 patients (50%) were dosed incorrectly with apixaban. (Figure 1). Conclusion: We demonstrate that there is significant variance in the dosing practice of direct oral anticoagulants among patients with advanced chronic kidney disease and end-stage renal disease. We hope to develop a checklist within the electronic medical record to promote adherence to guidelines when determining whether a patient requires dose reduction in the setting of renal dysfunction. Further investigation is being carried out to determine differences in outcomes among those properly dosed and those incorrectly dosed.