Inappropriate Dosing of Direct Oral Anticoagulants in Patients with Atrial Fibrillation

Sugrue, Alan; Sanborn, David; Amin, Mustapha; Farwati, Medhat; Sridhar, Haarini; Ahmed, Azza M.; Mehta, Ramila A.; Siontis, Konstantinos C.; Mulpuru, Siva K.; Deshmukh, Abhishek; Gersh, Bernard J.; Asirvatham, Samuel J.; Madhavan, Malini

doi:10.1016/j.amjcard.2020.12.062

Cited by 37 publications

(34 citation statements)

References 23 publications

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“…The DOAC's inappropriate dosage did not seem correlated to the incidence both thromboembolic and MB events; however, the underdosage group showed a significatively lower survival compared with appropriate dose group. Previous studies including younger AF cohorts on DOACs therapy reported a prevalence of inappropriate underdosage ranging from 14 to 45% [12,[18][19][20][21][22] and a prevalence of overdosage ranging from 2.40 to 14% [10][11][12]; our data confirmed these prevalences among octogenarians with AF.…”

Section: Discussionsupporting

confidence: 88%

“…In our analysis age, gender male and BMI were negatively associated with overdosage; in particular, younger patients, female and those with lower BMI would be more likely to have an inappropriate overdosage prescription among octogenarians with AF. Moreover, we showed that diabetes mellitus was an independent predictor of inappropriate DOACs' overdosage, according to previous evidence [10]. This data might be explained by the increased risk of ischemic cerebrovascular disease or stroke among AF patients with diabetes [25].…”

Section: Discussionsupporting

confidence: 78%

“…According to the analysis of Sugrue et al [10], the underdosage was independently associated with male gender. Other studies, including younger patients, showed female subjects received more frequently inappropriate DOACs dose [12].…”

Section: Discussionmentioning

confidence: 99%

“…In particular, DOACs showed higher net clinical benefit versus VKAs in octogenarians with AF both in trial [4][5][6][7] and in real-world setting [8,9]. Inappropriate dosage is a relevant issue affecting up to 15% of AF patients receiving DOACs [10] and the older age was associated with DOACs dosage not in compliance with the current recommendation [1,[10][11][12].…”

Section: Introductionmentioning

confidence: 99%

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Prevalence and clinical predictors of inappropriate direct oral anticoagulant dosage in octagenarians with atrial fibrillation

Carbone

Santelli

Bottino

et al. 2022

Eur J Clin Pharmacol

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Purpose Older age is associated with inappropriate dose prescription of direct oral anticoagulants. The aim of our study was to describe the prevalence and the clinical predictors of inappropriate DOACs dosage among octogenarians in real-world setting. Methods Data for this study were sourced from the multicenter prospectively maintained Atrial Fibrillation (AF) Research Database (NCT03760874). Of the AF patients aged ≥ 80 who received DOACs treatment, 253 patients were selected. Participants were categorized as appropriate dosage, overdosage, or underdosage. Underdosage and overdosage were, respectively, defined as administration of a lower or higher DOAC dose than recommended in the EHRA consensus. Results A total of 178 patients (71%) received appropriate DOACs dose and 75 patients (29%) inappropriate DOACs dose; among them, 19 patients (25.6%) were overdosed and 56 (74.4%) were underdosed. Subgroup analysis demonstrated that underdosage was independently associated with male gender [OR = 3.15 (95% IC; 1.45–6.83); p < 0.001], coronary artery disease [OR = 3.60 (95% IC 1.45–9.10); p < 0.001] and body mass index [OR = 1.27 (1.14–1.41); p < 0.001]. Overdosage was independently associated with diabetes mellitus [OR = 18 (3.36–96); p < 0.001], with age [OR = 0.76 (95% IC; 0.61–0.96; p = 0.045], BMI [OR = 0.77 (95% IC; 0.62–0.97; p = 0.043] and with previous bleedings [OR = 6.40 (0.7; 1.43–28); p = 0.039]. There wasn’t significant difference in thromboembolic, major bleeding events and mortality among different subgroups. Underdosage group showed a significatively lower survival compared with appropriate dose group (p < 0.001). Conclusion In our analysis, nearly one-third of octogenarians with AF received an inappropriate dose of DOAC. Several clinical factors were associated with DOACs’ overdosage (diabetes mellitus type II, previous bleeding) or underdosage (male gender, coronary artery disease, and higher body mass index). Octogenarians with inappropriate DOACs underdosage showed less survival.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Prevalence and clinical predictors of inappropriate direct oral anticoagulant dosage in octagenarians with atrial fibrillation

Carbone

Santelli

Bottino

et al. 2022

Eur J Clin Pharmacol

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“…Concerning evaluation of the appropriateness of dosing, the incidence of off-label use in our study was 23.8%, being underdosing much more common (22%) than over-dosing (1.8%). This numbers are in line with previous studies reporting non-recommended dosing in up to 30% of NVAF patients, the majority due to underdosing [40,49,50,51,52,53]. A bias towards greater concern of bleeding amongst physicians might be a main underlying factor [54].…”

Section: Discussionsupporting

confidence: 89%

Direct Oral Anticoagulants in Patients with Nonvalvular Atrial Fibrillation: A Real-World Experience from a Single Spanish Regional Hospital

Rodilla¹,

Orts-Martinez²,

Sanz-Caballer³

et al. 2021

Preprint

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The aim is to evaluate a program for direct oral anticoagulants (DOACs) management in nonvalvular atrial fibrillation (NVAF) patients, according to patient profiles, appropriateness of dosing, patterns of crossover, effectiveness and safety. This is an observational and longitudinal retrospective study in a cohort of patients attended in daily clinical practice in a single regional hospital in Spain with a systematic follow-up plan for up to 3 years for patients initiating dabigatran, rivaroxaban or apixaban between JAN/2012-DEC/2016. We analyzed 490 episodes of treatment (apixaban 2.5 mg: 9.4%, apixaban 5 mg: 21.4%, dabigatran 75 mg: 0.6%, dabigatran 110 mg: 12,4%, dabigatran 150 mg: 19.8%, rivaroxaban 15 mg: 17.8% and rivaroxaban 20 mg: 18.6%) in 445 patients. 13.6% of patients on dabigatran, 9.7% on rivaroxaban, and 3.9% on apixaban, switched to other DOACs or changed dosing. Apixaban was the most frequent DOAC switched to. The most frequent reasons for switching were toxicity (23.8%), bleeding (21.4%) and renal deterioration (16.7%). Inappropriateness of dose was found in 23.8% of episodes. Patients taking apixaban 2.5 mg were older, had higher CHA2DS2VASc score and lower creatinine clearance. Patients taking dabigatran 150 mg and rivaroxaban 20 mg were younger, had lower CHA2DS2VASc and higher creatinine clearance. Rates of stroke/transient ischemic attack (TIA) were 1.64/0.54 events/100 patients-years, while rates of major, clinically relevant non-major (CRNM) bleeding and intracranial bleeding where 2.4, 5, and 0.5 events/100 patients-years. Gastrointestinal and genitourinary bleeding were the most common type of bleeding events (BE). On multivariable analysis, prior stroke (RR: 4.2; CI: 1.5-11.8; p=0.006) and age (RR: 1.2; CI: 1.1-1.4; p=0.006) were independent predictors of stroke/TIA. Concurrent platelet inhibitors (RR: 7.1; CI: 2.3-21.8; p=0.001), male gender (RR: 2.1; CI: 1.2-3.7; p=0.0012) and age (RR: 1.1; CI: 1.02-1.13; p=0.005) were independent predictors of BE. This study complements the scant data available on the use of DOACs in NVAF patients in Spain, confirming a good safety and effectiveness profile

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Analysis of Oral Anticoagulant Dosing and Adherence to Therapy Among Patients With Nonvalvular Atrial Fibrillation

et al. 2023

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ImportanceAlthough reduced doses of direct oral anticoagulants (DOACs) are approved for patients with nonvalvular atrial fibrillation (NVAF) at high risk of bleeding, little is known about dosing accuracy, particularly in patients with renal dysfunction.ObjectiveTo determine whether underdosing of DOACs is associated with longitudinal adherence to anticoagulation.Design, Setting, and ParticipantsThis retrospective cohort analysis used data from the Symphony Health claims data set. This national medical and prescription data set comprises 280 million patients and 1.8 million prescribers in the US. Patients included had at least 2 claims for NVAF between January 2015 and December 2017. The dates of analysis for this article were from February 2021 to July 2022.ExposuresThis study included patients with CHA2DS2-VASc scores of 2 or higher who were treated with a dose of DOACs who did and did not meet label-specified criteria for dose reduction.Main Outcomes and MeasuresLogistic regression models examined factors associated with off-label dosing (ie, dosing not recommended by US Food and Drug Administration [FDA] labeling), the association of creatinine clearance with recommended DOAC dosing, and the association of DOAC underdosing and excess dosing with 1-year adherence.ResultsAmong the 86 919 patients included (median [IQR] age, 74 [67-80] years; 43 724 men [50.3%]; 82 389 White patients [94.8%]), 7335 (8.4%) received an appropriately reduced dose, and 10 964 (12.6%) received an underdose not consistent with FDA recommendations, meaning that 59.9% (10 964 of 18 299) of those who received a reduced dose received an inappropriate dose. Patients who received off-label doses of DOACs were older (median [IQR] age, 79 [73-85] vs 73 [66-79] years) and had higher CHA2DS2-VASc scores (median [IQR], 5 [4-6] vs 4 [3-6]) compared with patients who received appropriate doses (as recommended by FDA labeling). Renal dysfunction, age, heart failure, and the prescribing clinician being in a surgical specialty were associated with dosing not recommended by FDA labeling. Almost one-third of patients (9792 patients [31.9%]) with creatinine clearance less than 60 mL per minute taking DOACs were either underdosed or excess-dosed not consistent with FDA recommendations. For every 10-unit decrease in creatinine clearance, the odds of the patient receiving an appropriately dosed DOAC was lower by 21%. Treatment with underdosed DOACs was associated with a lower likelihood of adherence (adjusted odds ratio, 0.88; 95% CI, 0.83-0.94) and higher risk of anticoagulation discontinuation (adjusted odds ratio, 1.20; 95% CI, 1.13-1.28) by 1 year.Conclusions and RelevanceIn this study of oral anticoagulant dosing, DOAC dosing that did not follow FDA label recommendations was observed in a substantial number of patients with NVAF, occurred more frequently in patients with worse renal function, and was associated with less-consistent long-term anticoagulation. These results suggest a need for efforts to improve the quality of DOAC use and dosing.

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Inappropriate Dosing of Direct Oral Anticoagulants in Patients with Atrial Fibrillation

Cited by 37 publications

References 23 publications

Prevalence and clinical predictors of inappropriate direct oral anticoagulant dosage in octagenarians with atrial fibrillation

Prevalence and clinical predictors of inappropriate direct oral anticoagulant dosage in octagenarians with atrial fibrillation

Direct Oral Anticoagulants in Patients with Nonvalvular Atrial Fibrillation: A Real-World Experience from a Single Spanish Regional Hospital

Analysis of Oral Anticoagulant Dosing and Adherence to Therapy Among Patients With Nonvalvular Atrial Fibrillation

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