The Comparison of Inappropriate-Low-Doses Use among 4 Direct Oral Anticoagulants in Patients with Atrial Fibrillation: From the Database of a Single-Center Registry

Sato, Takao; Aizawa, Yoshifusa; Fuse, Koichi; Fujita, Satoshi; Ikeda, Yoshio; Kitazawa, Hitoshi; Takahashi, Minoru; Okabe, Masaru

doi:10.1016/j.jstrokecerebrovasdis.2018.07.028

Cited by 43 publications

(48 citation statements)

References 27 publications

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“…In this study, approximately 30% of patients received inappropriate doses of DOACs according to the approved Japanese recommendations. As shown in a previous study, in which the majority of the patients on inappropriate doses of DOACs were found to be on a lower dose than recommended, we also found that under‐treatment was more frequent than an over‐treatment in this setting. This is probably due to the fear of bleeding complications.…”

Section: Discussionsupporting

confidence: 85%

Evaluation of oral anticoagulants in atrial fibrillation patients over 80 years of age with nonsevere frailty

Shinohara

Wada

Yao

et al. 2019

Journal of Arrhythmia

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Background The safety and efficacy of an oral anticoagulant (OAC) treatment and the difference between direct OACs (DOACs) and warfarin in nonsevere frail elderly patients with AF are unclear. Methods This was a retrospective and observational study of 354 patients over 80 years of age with nonsevere frailty who were diagnosed with AF and treated with OACs. Nonsevere frailty was defined as a clinical frailty scale score of <7. Bleeding and thromboembolic events during the OAC treatment were followed up. Results Of 354 patients enrolled, 273 (77.1%) received DOACs and 81 (22.9%) received warfarin. Of 273 patients receiving DOACs, there were 210 (76.9%) prescribed with appropriate doses of DOACs. Of 81 warfarin‐treated patients, 53 (65.4%) were prescribed an appropriate dose of warfarin. During a follow‐up of 33.1 (14.0‐51.0) months, 15 patients (1.5/100 person‐years) had bleeding events and 10 (1.0/100 person‐years) had thromboembolic events while on an OAC treatment. The incidence ratio of bleeding events in patients receiving DOACs was lower than that in those receiving warfarin (1.0/100 person‐years vs 2.9/100 person‐years, hazard ratio [HR]: 0.26, 95% confidence interval [CI]: 0.07‐0.91, P = .036). There was no significant difference in the incidence of thromboembolic events between the DOAC and warfarin treatment groups (0.88/100 person‐years vs 1.4/100 person‐years, HR: 0.63, 95% CI: 0.16‐2.57, P = .52). Conclusions OACs are substantially safe and effective for preventing thromboembolic events in nonsevere frail patients over 80 years of age. Particularly, DOACs can be used more safely than warfarin.

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Section: Discussionsupporting

confidence: 85%

Evaluation of oral anticoagulants in atrial fibrillation patients over 80 years of age with nonsevere frailty

Shinohara

Wada

Yao

et al. 2019

Journal of Arrhythmia

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“…The SAKURA AF Registry revealed that inappropriate doses of DOACs were prescribed in 26.2% patients (underdosing in 22.2% and overdosing in 4.0% of patients, respectively) [6,15]. Furthermore, a retrospective cohort study conducted at a single Japanese center showed that 22.6% of patients receiving DOACs were inappropriately prescribed, with 21.3% underdosed and 1.3% overdosed [7]. These results indicated that an inappropriate dose of a DOAC was prescribed in approximately 1 in 4 or 5 AF patients in Japan, which is in accordance with our results.…”

Section: Discussionmentioning

confidence: 99%

“…This may be because Asians have been reported to have a higher risk of intracranial hemorrhage during anticoagulant therapy with warfarin than non-Asians [22], thus physicians in Japan may have greater concerns regarding bleeding risk. Sato et al revealed that the HAS-BLED score, which is a practical risk score for estimating the risk for major bleeding in AF patients, is an independent predictor of underdosing for apixaban (OR 1.59, 95% CI 1.18-2.13) and rivaroxaban (OR 2.27, 95% CI 1.51-3.39) [7]. This is in accordance with our results that the inappropriate dosing of DOACs was significantly associated with higher HAS-BLED scores (OR 1.87, 95% CI 1.42-2.51).…”

Section: Discussionmentioning

confidence: 99%

“…However, the dosing of these drugs should be appropriately adjusted based on one or more clinical features such as renal function, age, body weight, and concomitant drug use. In Japan, the prescription dose for each DOAC is determined by the manufacturer's recommendations in the drug package insert, and the physician's prescription is usually audited by pharmacists; however, physicians occasionally prescribe inappropriate doses of DOACs in real-world clinical settings [5][6][7]. Because few hospitals in Japan describe clinical laboratory data for out-of-hospital prescriptions, proper dosing adjustments may not be performed with prescriptions for outpatients compared with those for inpatients [8].…”

Section: Introductionmentioning

confidence: 99%

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Inappropriate direct oral anticoagulant dosing in atrial fibrillation patients is associated with prescriptions for outpatients rather than inpatients: a single-center retrospective cohort study

Miyazaki

Matsuo

Uchiyama

et al. 2020

J Pharm Health Care Sci

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Background: Inappropriate dosing of direct oral anticoagulants (DOACs) has been associated with clinical safety and efficacy; however, little is known about clinical data associated with an inappropriate DOAC dosing in Japan. In addition, there is no report in which the appropriateness of DOAC dosing between prescription for inpatients and for outpatients was examined. In this study, we aimed to investigate the prevalence and factors associated in the inappropriate dosing of DOACs in patients with atrial fibrillation (AF).Methods: The retrospective cohort study was conducted at a single Japanese university hospital. Both inpatients and outpatients, who were diagnosed with AF and for whom treatment with either dabigatran, rivaroxaban, apixaban, or edoxaban was initiated between April 1, 2014 and March 31, 2018, were enrolled in the study. Appropriateness of DOAC dosing was assessed according to the manufacturer's labeling recommendations (dose reduction criteria) of each DOAC. Inappropriate reduced dose, namely, underdosing, was defined as prescription of a reduced dose of DOAC despite the patient not meeting the dose reduction criteria. Inappropriate standard dose, namely, overdosing, was defined as prescription of a standard dose of DOAC despite the patient meeting the dose reduction criteria. Inappropriate DOAC dosing was defined as a deviation of the recommended dose (both underdosing and overdosing). Results: A total of 316 patients (dabigatran, 28; rivaroxaban, 107; apixaban, 116; and edoxaban, 65) were included, with a median (interquartile range) age of 75 (66-81) years and 62.3% male. DOACs were prescribed at an appropriate standard dose in 39.2% of patients, an appropriate reduced dose in 36.7%, an inappropriate standard dose in 2.5%, and an inappropriate reduced dose in 19.3%. Multivariate analysis revealed that the inappropriate dosing of DOACs was significantly associated with prescriptions for outpatients (vs. inpatients; odds ratio [OR] 2.87, 95% confidence interval [CI] 1.53-5.62, p < 0.001) and those with higher HAS-BLED scores (OR 1.87, 95% CI 1.42-2.51, p < 0.001).

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“…These patients were older, had a higher rate of previous bleedings, and a higher HAS-Bled score. In a single-center experience, 23% of patients were either under- or overdosed with NOACs [ 18 ]. In larger populations, the rate of inappropriate dosing of apixaban ranged between 15 and 20% [ 19 – 21 ].…”

Section: Discussionmentioning

confidence: 99%

Use, Persistence, Efficacy, and Safety of Apixaban in Patients with Non-Valvular Atrial Fibrillation in Unselected Patients in Germany. Results of the Prospective Apixaban in Atrial Fibrillation (APAF) Registry

et al. 2020

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Introduction Apixaban has been shown to be superior to warfarin in patients with non-valvular atrial fibrillation in the randomized ARISTOTLE trial and its use is recommended in current guidelines. There are only scarce data about its use, efficacy, and safety in unselected patients in Germany. Methods and Results The APAF registry is a prospective non-interventional study enrolling 5015 patients with non-valvular atrial fibrillation. Of these, 1349 (26.9%) patients were initially treated with apixaban and followed up at 3 and 12 months. The dose of apixaban used was 1 × 2.5 mg in 1.6%, 2 × 2.5 mg in 30.4%, and 2 × 5 mg daily in 68.0% of patients, respectively. Inappropriate underdosing of apixaban was observed in 22.3%, mostly in elderly patients with higher HAS-BLED Score and a history of bleeding. Persistence to apixaban after 1 year was 88.6%, while the dose was changed in 3.7% of patients. Switching to other NOACs or VKAs occurred in 5.1%. After 12 months, all-cause mortality was 5.0%, non-fatal stroke occurred in 0.4%, non-fatal myocardial infarction in 0.6%, ISTH major bleeding in 0.8%, moderate or minor bleeding in 4.3% of patients, respectively. Conclusions In this prospective experience in unselected patients with atrial fibrillation, persistence to apixaban was high, and efficacy and safety were comparable to the results in clinical trials, supporting its use in clinical practice. Electronic supplementary material The online version of this article (10.1007/s40119-020-00188-1) contains supplementary material, which is available to authorized users.

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The Comparison of Inappropriate-Low-Doses Use among 4 Direct Oral Anticoagulants in Patients with Atrial Fibrillation: From the Database of a Single-Center Registry

Cited by 43 publications

References 27 publications

Evaluation of oral anticoagulants in atrial fibrillation patients over 80 years of age with nonsevere frailty

Evaluation of oral anticoagulants in atrial fibrillation patients over 80 years of age with nonsevere frailty

Inappropriate direct oral anticoagulant dosing in atrial fibrillation patients is associated with prescriptions for outpatients rather than inpatients: a single-center retrospective cohort study

Use, Persistence, Efficacy, and Safety of Apixaban in Patients with Non-Valvular Atrial Fibrillation in Unselected Patients in Germany. Results of the Prospective Apixaban in Atrial Fibrillation (APAF) Registry

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