Doses Of Oral Anticoagulants Research Articles

Predictors and Outcomes of Inappropriate Dosing of Direct Oral Anticoagulants in Patients Receiving Transcatheter Aortic Valve Implantation.

Direct oral anticoagulant (DOAC) dose adjustment is based on age, renal function, and body weight. There is a paucity of data describing the factors associated with the prescription of inappropriate dosage and their impact on clinical outcomes among patients receiving transcatheter aortic valve implantation (TAVI). In a single-center study, 432 patients who were on long-term DOAC therapy and underwent TAVI between 2015 and 2022 were included. We analyzed the predictors and outcomes of inappropriate dosing of DOACs; namely apixaban, dabigatran, edoxaban, and rivaroxaban. A composite endpoint, including all-cause mortality, life-threatening/major bleeding, stroke, peripheral thromboembolic complications, or myocardial infarction, was assessed after 1 year. In this TAVI cohort, inappropriate DOAC dosing was observed in 20.6% of patients. Inappropriate DOAC dosage was related to female gender (adj. odds ratio [OR] 2.72, 95% confidence interval [CI] 1.64-4.51, p < 0.001) as well as lower estimated glomerular filtration rate (eGFR) (adj. OR 0.99, 95% CI 0.98-1.00, p = 0.019), and to the administration of non-rivaroxaban DOACs (adj. OR 0.28, 95% CI 0.16-0.50, p < 0.001). After 1 year, patients on both appropriate and inappropriate DOAC dosage exhibited comparable rates of the composite endpoint (OR 0.88, 95% CI 0.53-1.46, p = 0.622). Old age (adj. OR 1.05, 95% CI 1.01-1.10, p = 0.018) as well as anemia (adj. OR 0.86, 95% CI 0.75-0.99, p = 0.031) emerged as independent predictors of the composite endpoint. In this TAVI cohort, female gender and renal insufficiency were associated with inappropriate DOAC dosage, whereas rivaroxaban was linked to appropriate dosing. Inadequate DOAC dosage did not translate into a worse outcome in our TAVI population. Prospective Segeberg TAVI Registry (ClinicalTrials.gov identifier: NCT03192774).

Inappropriate dosing of direct oral anticoagulants in patients with atrial fibrillation undergoing percutaneous coronary intervention

Abstract Background Underdose (inappropriate low-dose) of direct oral anticoagulants (DOAC) is sometimes prescribed due to concerns of bleeding risk in patients with atrial fibrillation (AF). In AF patients with coronary artery disease requiring percutaneous coronary intervention (PCI), careful treatment is required to prevent bleeding events because of intensive antithrombotic therapy with a combination of oral anticoagulants and antiplatelet agents. Purpose The purpose of this study was to investigate the prevalence of underdose of DOAC and its impact on clinical outcomes in AF patients with coronary artery disease undergoing PCI. Methods This multicenter observational cohort study enrolled patients with AF on DOAC undergoing PCI between January 2015 and March 2021 at 15 institutions. Appropriateness of DOAC dose was determined according to the manufacturer's labeling recommendations in Japan. Clinical outcomes within 1 year, including major adverse cardiovascular events (MACE), all-cause mortality, ischemic stroke, and major bleeding events, were evaluated. Results Of 630 patients enrolled, 168 patients (26.7%) received underdose, 227 (36.0%) received appropriate low-dose, 213 (33.8%) received appropriate standard-dose, and 22 (3.5%) received overdose. Because of the extremely small number of patients in the overdose group, the primary analysis of the present study was a comparison between the underdose group (n=168) and the appropriate dose group (appropriate low-dose and standard-dose groups) (n=440). Although the incidence of MACE, all-cause mortality, and major bleeding events was not significantly different between the 2 groups (log-rank p=0.872, p=0.170, and p=0.725), ischemic stroke more frequently occurred in the underdose group compared with the appropriate dose group (log-rank p=0.010) (Figure 1). The multivariable Cox regression analysis determined underdose of DOAC as an independent predictor for ischemic stroke (adjusted HR 3.288, 95% CI: 1.189-9.088, p=0.022). Conclusions Compared with appropriate dose of DOAC, underdose was associated with a higher incidence of ischemic stroke, despite no significant difference in MACE, all-cause mortality, and major bleeding events, in AF patients undergoing PCI.Figure 1

Clinical outcomes of edoxaban treatment in atrial fibrillation patients with high bleeding risk: insights from the ETNA-AF-China 1-year follow-up

Abstract Background In China and many other countries, anticoagulated atrial fibrillation (AF) patients with high bleeding risk often raises clinical concern; the optimal dose of direct oral anticoagulants (DOACs) preventing stroke/systemic embolic events (SEE) in those population remains unclear. Purpose To assess the effectiveness and safety of edoxaban treatment in Chinese AF patients with high bleeding risk, and to compare 60 mg vs 30 mg dose in this real-world registry. Methods ETNA-AF-China is a prospective, observational study conducted in 89 centres across Chinese Mainland enrolling AF patients receiving edoxaban. This subgroup analysis was based on 1-year follow-up data. Patients were categorized to high bleeding risk group who had a DOAC score ≥6 (age, creatinine clearance, underweight, history of stroke/TIA/SEE, diabetes, hypertension, antiplatelet use, NSAIDs use, history of major/critical bleeding, liver disease) at baseline, or moderate-to-low bleeding risk group meeting criteria of DOAC score &amp;lt;6. The safety, effectiveness, and composite outcomes were reported by comparison between patient subgroups using Cox proportional hazards models. Results Of 4883 patients with 1-year follow-up, 1534 (31.4%, 60 mg: n=518, 30 mg: n=1016) were identified as high bleeding risk and 3349 (68.6%) as moderate-to-low bleeding risk. As expected, patients with high bleeding risk were more often elderly (48.2% ≥80 years), had lower body weight, worse renal function, higher CHA2DS2-VASc score than those with moderate-to-low risk (Figure 1). In both high risk and moderate-to-low risk subgroups, patients receiving 60 mg edoxaban were younger, with better renal function, lower CHA2DS2-VASc score compared with 30 mg. Annualised event rates of major bleeding (HR 2.95, 95%CI 1.62–5.36), all cause death (3.42, 2.29–5.09), CV death (3.27, 1.52–7.04), major adverse cardiac events (MACE, 2.61, 1.69–4.02) and all NCOs were significant higher in patients with high bleeding risk compared with moderate-to-low risk (Figure 2). After multivariable adjustment, edoxaban dose of 60 mg other than 30 mg were associated with significantly lower rates of all cause death (adjusted HR 0.41, 0.18–0.90) and lower trend of NCO3 (0.51, 0.28–0.92) and NCO4 (0.51, 0.30–0.88) by composite of stroke/SEE, major bleeding and death events in high risk subgroup; no significant difference between edoxaban doses and stroke or bleeding outcomes with cumulative low event rates were observed. Conclusion In routine clinical care, AF patients at high bleeding risk faces worse outcomes of death events, MACE, as well as the composite outcomes over moderate-to-low risk patients. Among patients with high bleeding risk, edoxaban use showed effectiveness and safety with overall low incidence, and potential better survival, composite endpoint benefit could be associated with 60mg. Further investigation is ongoing.

Appropriateness of direct oral anticoagulant dosing in patients with atrial fibrillation at a tertiary care hospital in Thailand

BackgroundAppropriate dosing of direct oral anticoagulants (DOACs) has been associated with clinical efficacy and safety. Several studies have shown that DOAC dosing are often inconsistent with guideline recommendations. Little is known about this issue in Thailand. This study aimed to evaluate the appropriateness of DOAC dosing in Thai hospitalized patients with atrial fibrillation (AF). MethodThis was a retrospective descriptive study conducted on hospitalized patients at Rajavithi Hospital, a tertiary care hospital in Thailand. Inpatients diagnosed with AF and treated with DOACs between February 2021 and February 2023 were enrolled in the study. The appropriate dosing of DOACs was assessed according to the recommendation of the 2021 European Heart Rhythm Association Practical Guide on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation (EHRA). Descriptive statistics were used to analyze the data; median (interquartile range) for continuous variables, and numbers and percentages for categorical variables. ResultsA total of 120 patients with AF were evaluated for dosing. The patients received rivaroxaban in 47 cases (39.2 %), apixaban in 32 cases (26.7 %), edoxaban in 31 cases (25.8 %), and dabigatran in 10 cases (8.3 %). Most of the patients were elderly, with a median age of 77.5 (68–84) years. Females were predominant (57.5 %). Our findings indicate that the prevalence of appropriate dosing of DOACs was 63.3 %. However, approximately one-third of patients received inappropriate dosing, with 24 (20.0 %) being overdosed, and 20 (16.7 %) being underdosed. The highest overdosing and underdosing rates were seen in dabigatran (90.0 %) and apixaban (21.9 %), respectively. ConclusionInappropriate dosing of DOACs according to the 2021 EHRA recommendations was high in 36.7 %, with overdosing mostly occurring in 20.0 %. The high number of inappropriate dosing highlights the need for implementation of optimal strategies to select the appropriate dose of DOACs in Thai hospitalized patients with AF.

Timing of Off-Label Dosing of Direct Oral Anticoagulants in Three Large Health Systems.

While direct oral anticoagulants (DOACs) may be viewed as simpler to manage then warfarin, they present their own unique management challenges resulting in frequent off-label dosing. It is unknown to what extent off-label dosing occurs when a patient is started on a DOAC versus later in their treatment. We aimed to better characterize when off-label DOAC dosing is occurring and to evaluate the effectiveness of prescribing oversight using a registry-based intervention. We evaluated data from the Michigan Anticoagulation Quality Improvement Initiative (MAQI2) registry, a retrospective quality-improvement process using data abstractors, from 2018 to 2022 on the number of "alerts" that are generated in response to dosing deviating from the U.S. Food and Drug Administration instructions for atrial fibrillation (AF) and venous thromboembolism (VTE). Among a sample of 789 to 1,022 annual AF patients and 381 to 484 annual VTE patients prescribed a DOAC in the MAQI2 registry, off-label dosing was relatively common. Over the 5-year period (2018-2022), there were 569 alerts for AF patients and 162 alerts for VTE patients. Alerts occurred more frequently during follow-up than at the time of initial prescribing in AF patients (78.2 vs. 21.8%), but more commonly at initial prescribing in VTE patients (59.9 vs. 40.1%). After initial review by quality-improvement abstractors, 19.3% of AF alerts and 14.8% of VTE alerts resulted in contact to the prescriber. When the prescriber was contacted, it led to an intervention about 75% of the time for both populations. The most common intervention was a change in DOAC dosing. This study demonstrates the benefit of DOAC prescribing oversight using a registry-based intervention to monitor for off-label dosing for the entirety of the time period a patient is prescribed DOAC, particularly for patients with AF, as off-label prescribing occurs frequently during the follow-up period.

EGFR calculated from cystatin C: Implications for dosing of direct oral anticoagulants.

eGFR calculated from cystatin C: Implications for dosing of direct oral anticoagulants.

#1146 Role of renal dysfunction in the use of anticoagulants in COPD patients with atrial fibrillation

Abstract Background and Aims The renal dysfunction is known to be the most important predictor of outcome in patients with atrial fibrillation (AF). At the same time, assessment of the functional state of the kidneys is an integral part of the protocol when selecting the dose of oral anticoagulants. The prognostic role of the functional state of the kidneys during treatment with oral anticoagulants on a possible worsening of the cardiac prognosis during the treatment of AF in patients with concomitant comorbid background, in particular with COPD, has not been sufficiently studied. The aim of the study was to evaluate the prognostic role of renal dysfunction in terms of possible cardiovascular events and bleeding in patients with COPD and AF treated with oral anticoagulants. Method 56 COPD patients with CHF and AF who received oral anticoagulants were examined. Renal function (creatinine level and estimated glomerular filtration rate - eGFR) was assessed at baseline and follow-up. The functional state of the kidneys was calculated using the CKD-EPI-2011 formula. At baseline, the risk of bleeding was assessed using the HAS-BLED scale. Worsening of the functional state of the kidneys was detected when the level of creatinine increased or eGFR decreased by at least 20%. Results In addition to standard treatment for COPD in the presence of AF, patients received oral anticoagulants during six months of observation. Worsening of the functional state of the kidneys was observed in 18.3% of patients. In patients with renal dysfunction, the frequency of episodes of CHF decompensation and non-major bleeding (MB) was significantly higher. With a reduced glomerular filtration rate, there was no effect on the incidence of bleeding and stroke. The oral anticoagulants used did not have a significant effect on the observed renal dysfunction and did not affect the occurrence of new cardiovascular events in patients with COPD. It turned out that predictors of renal dysfunction in patients with COPD are age, female gender, and lower hemoglobin levels. In multivariate analysis, renal dysfunction was identified as an independent predictor of non-major bleeding (OR 2.04, 95%, p &amp;lt; 0.05). Conclusion In patients with COPD and atrial fibrillation, the presence of renal dysfunction was an additional exacerbating factor associated with a poor mid-term cardiovascular prognosis and the risk of bleeding. However, oral anticoagulants did not affect the degree of deterioration of renal function or the incidence of cardiovascular events.

Long-Term Efficacy and Safety of Direct Oral Anticoagulants at Reduced Doses in the Secondary Prevention of Venous Thromboembolism and Post-Thrombotic Syndrome.

Background: Anticoagulation for venous thromboembolism (VTE) is required for at least three to six months; however, it is advisable to extend the duration in certain cases, in which case a reduced dose of Direct Oral Anticoagulants (DOACs) may be an option. Our objective was to investigate the efficacy and safety of reduced-dose DOACs in extended anticoagulation treatment compared to full doses. Methods and Results: This retrospective single-centre study included 185 patients treated with DOACs for at least 6 months who were divided into two groups: (1) the Full Dose (FD) group (n = 113) and (2) the Reduced Dose (RD) group (n = 72), which included patients treated with Apixaban at 2.5 mg bis in die (BID) and Rivaroxaban at 10 mg once daily (OD). Post-thrombotic syndrome (PTS) and its progression were evaluated. During an overall follow-up of 48.32 ± 29.49 months, no VTE occurred, and no patients experienced major bleeding; clinically relevant non-major bleeding occurred in three patients in each group (2.7% vs. 4.2% in FD vs. RD, respectively, p = 0.57). From baseline to follow-up, the prevalence of PTS was not significantly decreased in either group (FD: 54.9% vs. 51.3%, p = 0.29; RD 51.4% vs. 44.4%, p = 0.12); conversely, the Villalta score values were significantly decreased at the last follow-up (FD: 5.51 ± 4.18 vs. 5.12 ± 4.36, p < 0.001; RD 5.49 ± 4.06 vs. 5.11 ± 3.73, p = 0.006). Conclusion: In this real-world retrospective registry, very long-term extended anticoagulant therapy with DOACs at full or reduced doses showed comparable efficacy, safety, and impact on PTS progression. Larger studies are needed.

Unapproved Dose of Direct Oral Anticoagulants for Venous Thromboembolism - Right or Wrong?

Unapproved Dose of Direct Oral Anticoagulants for Venous Thromboembolism - Right or Wrong?

Comparison of different direct oral anticoagulant regimens in atrial fibrillation patients with high bleeding risk

BackgroundThe optimal dose of direct oral anticoagulants (DOACs) to prevent ischemic stroke (IS) and systemic thromboembolism (STE) in atrial fibrillation (AF) patients with a predisposing bleeding risk remains unclear. ObjectiveThe purpose of this study was to compare the effectiveness and safety of different DOAC dosage regimens in AF patients with high bleeding risk but low thrombosis risk. MethodsThis retrospective observational study was conducted with the National Health Insurance claims database in Taiwan to include AF patients aged 20 up to 75 years, under DOAC therapy, with CHA2DS2-VASc score of 1 for males and 2 for females and HAS-BLED score ≥3. Standard-dose regimen was defined as dabigatran 300 mg, rivaroxaban 20 mg, apixaban 10 mg, or edoxaban 60 mg per day. Any other lower-dose regimen were defined as the low-dose regimen. The primary outcomes were IS and major bleeding (MB). The secondary outcomes were STE, gastrointestinal bleeding, intracranial hemorrhage, and cardiovascular death. ResultsA total of 964 patients were included (52.1% standard-dose regimen). Median HAS-BLED score was 3 [interquartile range 3–3]. Compared with standard-dose group, patients in the low-dose group had a significantly increased risk of IS (adjusted hazard ratio [aHR] 5.13; 95% confidence interval 1.37–19.22) and STE (aHR 3.14 [1.05–9.37]) but similar risk of MB (aHR 0.45 [0.12–1.67]). The risks of other hemorrhage and cardiovascular death were similar between the 2 dose groups. ConclusionAmong patients with a predominant bleeding risk but relatively low thrombosis risk, the low-dose DOAC regimen is not a more appropriate selection than standard-dose regimen.

Assessment and predictors of inappropriate dose of direct oral anticoagulants

Direct-Acting Oral Anticoagulants (DOACs) have revolutionized the management of Atrial Fibrillation (AF) and Venous Thromboembolism (VTE). However, recent audits reveal a significant burden of inappropriate dosages in the prescribing of direct-acting oral anticoagulants. Our aim is to identify the prevalence and predictors of such inappropriate dosing in our patients. This retrospective study was conducted from June 2016 to January 2018. Patients who received dabigatran, rivaroxaban, or apixaban for treatment of venous thromboembolism or atrial fibrillation were included. Appropriateness of direct-acting oral anticoagulants dosing was assessed using US Food and Drug Administration guidelines. Data was analyzed using IBM® SPSS Version 26. 337 patients were included, with a mean age of 62.9±18.7 years. The majority were female (196, 58.3%). Of the patients, 194 (57.6%) received apixaban, 99 (29.4%) received rivaroxaban, and 44 (13.1%) received dabigatran. A total of 242 (71.8%) patients were prescribed direct-acting oral anticoagulants appropriately. Under-dosing and over-dosing were identified in 74 (22%) and 21 (6.2%) patients, respectively. Predictors of inappropriate dosing were age greater than 75 years (OR: 2.76, 95% CI: 1.67-4.56, p&lt;0.001) and creatinine clearance less than 50 ml/minute (OR: 0.38, 95% CI: 0.19-0.74, p: 0.005). Inappropriate dosing was significantly associated with mortality (p=0.010).One-third of our patients received an inappropriate dose of direct-acting oral anticoagulants, mostly from underdosing. Elderly age and low creatinine clearance are significant predictors of inappropriate dose administration.

Appropriate Use of Anticoagulants among Nonvalvular Atrial Fibrillation Patients at a University Hospital in Thailand

OBJECTIVE: Warfarin is primarily used for stroke prevention in atrial fibrillation (AF) patients in Thailand. Novel oral anticoagulants (NOACs) are used less commonly due to their high cost. This study aimed to evaluate the appropriate use of anticoagulants and clinical outcomes among nonvalvular AF (NVAF) patients. METHODS: This retrospective study collected data from the electronic medical records of patients who were diagnosed with NVAF between January 2014 and December 2019 at the Faculty of Medicine, Vajira Hospital. Baseline characteristics, prescribed indication, types and doses of anticoagulant, and ischemic and hemorrhagic outcomes were recorded and analyzed. RESULTS: We analyzed 783 patients with NVAF in this study. Of these, 539 (68.90%) were treated with oral anticoagulants (OAC), including 344 patients (43.90%) with warfarin therapy and 195 (24.90%) with NOACs. Meanwhile, 492 (73.10%) patients with CHA2DS2VASC score ≥ 2 received OAC therapy that was suitable for their indication. Of the 344 patients who received warfarin, 112 patients (32.60%) had an optimal time in therapeutic range (TTR) level of ≥ 65%. Of the 195 NOAC patients, only 98 (50.30%) received appropriate doses of NOACs. There was no statistically significant difference in the overall incidence rates of ischemic stroke/systemic embolism, bleeding, cardiovascular death, and all-cause death between the warfarin and NOACS groups. Appropriate TTR levels in the warfarin group was associated with significantly lower incidence rates of cardiovascular death (hazard ratio: 0.14; 95% CI: 0.02–0.79; p = 0.02) and all-cause death (hazard ratio: 0.36; 95% CI: 0.12–0.87; p = 0.01), than inappropriate TTR levels. CONCLUSION: Most NVAF patients received oral anticoagulants with the appropriate indication. Warfarin is the most prescribed oral anticoagulant for patients with NVAF. About half of the patients received inappropriate doses of oral anticoagulants that potentially adversely affected the study outcomes of cardiovascular and all-cause deaths.

Abstract 13741: Off-Label Dosing of Direct Oral Anticoagulants Among Inpatients With Atrial Fibrillation

Introduction: Among patients hospitalized for atrial fibrillation (AF), the frequency of off-label direct oral anticoagulant (DOAC) dosing, associated factors, hospital-level variation, and temporal trends in contemporary practice are unknown. Methods: Using the Get With The Guidelines® Atrial Fibrillation (GWTG-AF) registry, patients admitted from January 1 st , 2014 to March 31 st , 2020, and discharged on DOAC were stratified according to receipt of under, over, or recommended dose. Factors associated with off-label dosing were identified using logistic regression. Hospital-level variation and temporal trends were assessed. Results: Of 22,470 patients prescribed a DOAC at discharge from hospitalization (66% apixaban, 29% rivaroxaban, 5% dabigatran), underdosing occurred among 2006 (8.9%), overdosing among 511 (2.3%), and recommended dosing among 19953 (88.8%). Patient factors associated with off-label use included age (underdosing: OR 1.06 per 1-year increase [95% CI 1.06-1.07] and overdosing: OR 1.07 per 1-year increase [1.06-1.09]), dialysis dependence (underdosing: OR 5.50 [3.76-8.05] and overdosing: OR 5.47 [2.74-10.88]), female sex (overdosing: OR 0.79 [0.63-0.99]) and weight (overdosing: OR 0.96 per 1-Kg increase [0.95-1.00]). Across hospitals, the adjusted median odds ratio for off-label DOAC use was 1.45 [95% CI 1.34-1.65] (underdosing: 1.52 [1.39-1.76] and overdosing: 1.32 [1.20-1.84]), indicating significant hospital-level variation. Hospital characteristics associated with underdosing included West vs. Northeast location (OR: 1.55 [1.04-2.31]), rural vs. urban setting (OR: 0.48 [0.28-0.83]), and number of beds (&lt;200 vs. 500+, OR: 1.95 [1.29-2.95]). Recommended dosing significantly increased over time (81.9% in 2014 to 90.9% in 2020, p&lt;0.0001 for trend) with a corresponding decline in under (14.4% in 2014 to 6.6% in 2020, p&lt;0.0001 for trend) and overdosing (3.8% in 2014 to 2.5% in 2020, p=0.001 for trend). Conclusion: One of 10 patients hospitalized for atrial fibrillation is discharged on off-label dosing of DOAC with significant variation across hospitals. While the proportion of patients receiving recommended dosing has significantly improved over time, opportunities to improve DOAC dosing persist.

Abstract 14204: Efficacy and Safety of Low-Dose Edoxaban According to Body Weight in Very Elderly Patients With Atrial Fibrillation: A Sub-Analysis of the ELDERCARE-AF Trial

Background: The ELDERCARE-AF trial showed that low-dose edoxaban is beneficial in elderly patients with non-valvular atrial fibrillation (AF) who are considered ineligible candidates for standard oral anticoagulants (OACs) due to high bleeding risk, but it was not known whether this is the case in low-body-weight patients. Methods: This was a prespecified sub-analysis, by body weight (≤45 and &gt;45 kg), of the ELDERCARE-AF trial, a randomized, placebo-controlled trial comparing low-dose edoxaban (15 mg once daily) with placebo. All patients were of Japanese ethnicity and considered ineligible for standard doses of OACs. The primary efficacy endpoint was stroke or systemic embolism (SSE). The key secondary endpoints were all-cause mortality and net clinical outcome. The primary safety endpoint was major bleeding according to the definition of the International Society on Thrombosis and Hemostasis. Results: Of the 984 patients, 374 patients (38.0%) were in the ≤45 kg group and 610 (62.0%) patients were in the &gt;45 kg group. The SSE was lower with edoxaban than with placebo in both weight groups (≤45 kg group: hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.16-0.80; &gt;45 kg group: HR 0.31, 95% CI 0.13-0.73; interaction P 0.82). Both all-cause mortality and net clinical outcome were higher in the ≤45 kg group, with no significant difference between treatment groups. Major bleeding was numerically higher with edoxaban than with placebo (≤45 kg group: HR 3.05, 95% CI 0.84-11.11; &gt;45 kg group: HR 1.40, 95% CI 0.56-3.48), with no interaction with body weight (interaction P 0.33). Similar results were obtained in the exploratory analysis of patients divided into four quartiles of body weight (&gt;57.9, &gt;49.0 to ≤57.9, &gt;42.0 to ≤49.0, and ≤42.0 kg). Conclusions: The benefit of edoxaban 15 mg was consistent in elderly AF patients with low body weight, provided clinicians remain vigilant about the risk of major bleeding.

Off-Label Dosing of Direct Oral Anticoagulants Among Inpatients With Atrial Fibrillation in the United States.

Among patients hospitalized for atrial fibrillation, the frequency of off-label direct oral anticoagulant (DOAC) dosing, associated factors, hospital-level variation, and temporal trends in contemporary practice are unknown. Using the Get With The Guidelines-Atrial Fibrillation registry, patients admitted from January 1, 2014, to March 31, 2020, and discharged on DOACs were stratified according to receipt of underdosing, overdosing, or recommended dosing. Factors associated with off-label dosing (defined as underdosing or overdosing) were identified using logistic regression. Median odds ratio (OR) and time-series analyses were used to assess hospital-level variation and temporal trends, respectively. Of 22 470 patients (70.1±12.1 years, 48.1% female, 82.5% White) prescribed a DOAC at discharge from hospitalization for atrial fibrillation (66% apixaban, 29% rivaroxaban, and 5% dabigatran), underdosing occurred among 2006 (8.9%), overdosing among 511 (2.3%), and recommended dosing among 19 953 (88.8%). The overall rate of off-label dosing was 11.2%. Patient-related factors associated with off-label dose included age (underdosing: OR, 1.06 per 1-year increase [95% CI, 1.06-1.07]; overdosing: OR, 1.07 per 1-year increase [95% CI, 1.06-1.09]), dialysis dependence (underdosing: OR, 5.50 [95% CI, 3.76-8.05]; overdosing: OR, 5.47 [95% CI, 2.74-10.88]), female sex (overdosing: OR, 0.79 [95% CI, 0.63-0.99]), and weight (overdosing: OR, 0.96 per 1-kg increase [95% CI, 0.95-1.00]). Across hospitals, the adjusted median OR for off-label DOAC dose was 1.45 (95% CI, 1.34-1.65; underdosing: OR, 1.52 [95% CI, 1.39-1.76]; overdosing: OR, 1.32 [95% CI, 1.20-1.84]), indicating significant hospital-level variation. Over the study period, recommended dosing significantly increased over time (81.9%-90.9%; P<0.0001 for trend) with a corresponding decline in underdosing (14.4%-6.6%; P<0.0001 for trend) and overdosing (3.8%-2.5%; P=0.001 for trend). Over 1 in 10 patients hospitalized for atrial fibrillation are discharged on an off-label DOAC dose with significant variation across hospitals. While the proportion of patients receiving recommended dosing has significantly improved over time, opportunities to improve DOAC dosing persist.

Oral anticoagulants status after acute ischemic stroke and prognosis in patients with atrial fibrillation

ObjectivesTo investigate the oral anticoagulants (OACs) use after acute ischemic stroke (AIS) and prognosis of patients with atrial fibrillation (AF). MethodsThis was a real-world follow-up research of AIS patients with AF admitted to 5 hospitals in northwestern China. We visited these individuals every 6 months to check the type, dosage of OACs, and to record IS recurrence, bleeding, and death events and modified Rankin Scale (mRS) scores until December 2022. When one of the following occurring first was endpoint: IS recurrence, death or study end. Patients were divided into continuous anticoagulation group and non-continuous anticoagulation group based on whether they continued to take OACs from the moment they were discharged until the endpoint. We further analyzed the association between anticoagulation persistence and outcomes. ResultsAmong all 250 patients with OACs indication, 147 patients (58.8 %) received OACs at discharge. Only 37.9 % of patients (39/103) started OACs after discharge. Of the 147 patients treated with OACs, 21.8 % (32/147) discontinued anticoagulation after discharge. 239 of the 250 patients had completed the median 40-month follow-up with 91 patients in continuous anticoagulation group and 148 patients in non-continuous anticoagulation group. In the multivariate COX regression, non-continuous anticoagulation was an independent risk factor for poor prognosis (mRS>2) in AIS patients with AF (1.452[1.011, 2.086], p = 0.043). ConclusionsThis study revealed an upward trend in the use rate of OACs, but low OACs rates that meet guideline-based criteria and low anticoagulation persistence in AF patients after AIS in the northwestern China. Discontinuous anticoagulation was associated with an increased risk of poor prognosis in these patients.

Inappropriate dosing of direct oral anticoagulants: findings from a clinical vignette study and physician survey

ABSTRACT Objective Direct oral anticoagulants (DOACs) are first-line therapy for stroke prevention for 1.4 million atrial fibrillation (AF) patients in the UK. However, the rates of DOAC dosing below evidence-based recommendations are estimated between 9% and 22%. This study explores specific patient and physician factors associated with prescribing inappropriate DOAC underdoses. Methods DOAC-prescribing physicians within the UK completed both a clinical vignette survey, which contained 12 hypothetical patient profiles designed to replicate DOAC prescribing scenarios, and a physician survey to capture sociodemographic, clinical experience, and prescriber-related beliefs and motivations related to DOAC prescribing. Eight patient factors based on a literature search and an expert consultation process were varied within the vignettes. Associations between the prescribers’ dosing choices and patient factors were explored via multilevel logistic regression. The analysis is focused on the most frequently selected DOACs, apixaban and rivaroxaban, both of which have different dosing guidelines. Results In all, 336 prescribers (69% male; 233/336) completed the survey, mostly general physicians (GPs) (45%) or cardiology specialists (36%) with a mean of 17.9 years’ experience. Most prescribers (73%; 244/336) inappropriately underdosed at least once; rates between GPs and specialists were nearly identical. Patient factors most strongly associated with apixaban inappropriate underdosing included a history of major bleeding and falls. For rivaroxaban, these were major bleeding and severe frailty. Only 32% (106/335) of prescribers reported DOAC dosing guidelines as the sole influence on their prescribing behaviour. Among prescribers who did not inappropriately underdose, greater prescribing confidence was aligned to increased perception of inappropriate underdose risk. Conclusions Overall, patient factors such as major bleeding and severe frailty were found to be associated with inappropriate underdosing of apixaban and rivaroxaban. Furthermore, prescribers who were more confident in DOAC prescribing, and were more worried about the risk of stroke, were significantly less likely to inappropriately underdose. These findings suggest that all prescribers, regardless of speciality, may benefit from education and training to raise awareness of the risks associated with inappropriate DOAC underdosing.

Quantifying time from last dose: do direct oral anticoagulant assays correlate with patient's reported last dose.

In the absence of a patient's last direct oral anticoagulant (DOAC) dose time, best practice regarding preoperative DOAC cessation remains unclear. The aim of this study was to investigate, in a real-life patient cohort, if there was an association between subjective patient recall and objective DOAC assay titre. A multicentre cohort study of consecutive surgical inpatients was conducted. DOAC assays were 'expected' if they satisfied both time and titre-based guidelines. Patient-recalled last dose and DOAC assay was available in 285 individuals. DOAC assay titres correlated strongly with the expected levels based on a patient's reported last dose time(rho = 0.70, P value < 0.0001). However, underweight (<50 kg; P = 0.0339) and elderly (>80 years; P = 0.0134) were more likely to have an unexpectedly high assay titre. A significant portion (∼25%) of patients had unexpected DOAC titres. DOAC levels can be clinically impactful in a significant percentage of patients, particularly in elderly and/or underweight.

Safety and Efficacy of Direct Oral Anticoagulants Versus Warfarin for Atrial Fibrillation in End-Stage Renal Disease on Hemodialysis: A Meta-Analysis of Randomized Control Trials

End-stage renal disease (ESRD) and atrial fibrillation (AF) are commonly encountered, with ESRD itself serving as a well-established risk factor for AF.1 The 2018 AF guidelines have recommended apixaban across all the spectrums of renal impairment, including patients on hemodialysis (HD), and the 2019 American Heart Association/American College of Cardiology/Heart Rhythm Society updated guidelines have suggested careful consideration of reduced dose of direct oral anticoagulants (DOACs) in patients with ESRD.2,3 The current data on the safety and efficacy of warfarin versus DOACs in patients with AF with ESRD and HD is variable. This study aimed to perform a study-level meta-analysis to evaluate the effectiveness and safety of warfarin and DOACs in patients with AF who require dialysis.

Features of the use of oral anticoagulants in clinical practice: focus on gastrointestinal complications

The review article presents dates about the physiology and pathophysiology of the hemostasis system, discusses the features of the use of oral anticoagulants in clinical practice. Oral anticoagulants are drugs characterized by predictable pharmacokinetics and pharmacodynamics, a favorable efficacy and safety profile. The article considers the main clinical and pharmacological characteristics of apixaban, rivaroxaban and dabigatran (bioavailability, metabolism, excretion); factors that increase the risk of gastrointestinal bleeding associated with anticoagulant therapy; drug interactions; the possibility of gastroprotection in patients taking oral anticoagulants. In real clinical practice, the reason for not prescribing or unreasonably reducing the dose of oral anticoagulants is the fear of bleeding. In this case, the risks of bleeding, as a rule, are overestimated. Knowledge of bleeding risk factors, prognostic scales and management of risk factors is an approach that can improve the safety of anticoagulant therapy. In clinical practice, the choice of the ideal oral anticoagulants, in addition to taking into account the risk of bleeding, should be based on a comprehensive assessment, including an assessment of the patient's age, risk of stroke and coronary events, renal function, and predicted compliance.