Effect of Renal Function on Dosing of Non–Vitamin K Antagonist Direct Oral Anticoagulants Among Patients With Nonvalvular Atrial Fibrillation

Shrestha, S.; Başer, Onur; Kwong, Winghan Jacqueline

doi:10.1177/1060028017728295

Cited by 18 publications

(30 citation statements)

References 13 publications

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“…The discrepancy between the proportion of patients with changes in tablet strengths and the low proportion of patients with age and CKD related adjustments might be due to patients with an increase in tablet strength not being accounted for. Other studies have reported about 20% patients receiving inappropriate doses, most often too low (38%) or excessively high dose (22%) …”

Section: Discussionmentioning

confidence: 99%

“…However, little is known about their use beyond clinical trial conditions, especially in patients with hepatic or renal impairment. Findings from 2 studies from USA and Australia showed that inappropriate dosing occurred among patients with renal failure, and there is still uncertainty about appropriate dosing in these patients . In addition, the very elderly, who may be at increased risk of adverse effects with inappropriate DOAC use, are poorly represented in clinical trials …”

Section: Introductionmentioning

confidence: 99%

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Incidence of direct oral anticoagulant use in patients with nonvalvular atrial fibrillation and characteristics of users in 6 European countries (2008–2015): A cross‐national drug utilization study

Ibáñez

Sabaté

Vidal

et al. 2019

Brit J Clinical Pharma

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AimsTo estimate the incidence of direct oral anticoagulant drug (DOAC) use in patients with nonvalvular atrial fibrillation and to describe user and treatment characteristics in 8 European healthcare databases representing 6 European countries.MethodsLongitudinal drug utilization study from January 2008 to December 2015. A common protocol approach was applied. Annual period incidences and direct standardisation by age and sex were performed. Dose adjustment related to change in age and by renal function as well as concomitant use of potentially interacting drugs were assessed.ResultsA total of 186 405 new DOAC users (age ≥18 years) were identified. Standardized incidences varied from 1.93–2.60 and 0.11–8.71 users/10 000 (2011–2015) for dabigatran and rivaroxaban, respectively, and from 0.01–8.12 users/10 000 (2012–2015) for apixaban. In 2015, the DOAC incidence ranged from 9 to 28/10 000 inhabitants in SIDIAP (Spain) and DNR (Denmark) respectively. There were differences in population coverage among the databases. Only 1 database includes the total reference population (DNR) while others are considered a population representative sample (CPRD, BIFAP, SIDIAP, EGB, Mondriaan). They also varied in the type of drug data source (administrative, clinical). Dose adjustment ranged from 4.6% in BIFAP (Spain) to 15.6% in EGB (France). Concomitant use of interacting drugs varied between 16.4% (SIDIAP) and 70.5% (EGB). Cardiovascular comorbidities ranged from 25.4% in Mondriaan (The Netherlands) to 82.9% in AOK Nordwest (Germany).ConclusionOverall, apixaban and rivaroxaban increased its use during the study period while dabigatran decreased. There was variability in patient characteristics such as comorbidities, potentially interacting drugs and dose adjustment. (EMA/2015/27/PH).

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Incidence of direct oral anticoagulant use in patients with nonvalvular atrial fibrillation and characteristics of users in 6 European countries (2008–2015): A cross‐national drug utilization study

Ibáñez

Sabaté

Vidal

et al. 2019

Brit J Clinical Pharma

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“…Shrestha et al found no significant difference in stroke risk for both underdosed or overdosed patients compared with appropriately dosed patients taking NOACs for AF‐prevention. However, it was found that underdosed as well as overdosed patients have increased risk of bleeding compared with appropriately dosed ones . Hence, further research is required to prove the connection between off‐label dosing of rivaroxaban and patients' health.…”

Section: Discussionmentioning

confidence: 99%

“…As suggested by recently registered data, rivaroxaban is commonly dosed inadequately. Such cases occurred among patients with normal as well as insufficient renal function, causing potential over‐ or underdosing . Research provides information on how such instances influence drug's safety and effectiveness.…”

Section: Introductionmentioning

confidence: 99%

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Initial rivaroxaban dosing in patients with atrial fibrillation

Ablefoni

Buchholz

Ueberham

et al. 2019

Clinical Cardiology

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Background Rivaroxaban is a non‐vitamin K oral anticoagulant and has been approved for prevention of stroke and systemic embolism in patients with non‐valvular atrial fibrillation (AF). Current labeling recommends 20 mg once a day (q.d.) as a standard dose and a reduced dose of 15 mg q.d. in patients with renal impairment. Hypothesis The aim of this study was to analyze the adherence to current labeling concerning initial rivaroxaban dosing and to determine whether potential lack of such adherence is medically justified. Methods Patients with AF initiated on rivaroxaban between January 1, 2016 and January 31, 2017, were identified in the Heart Center Leipzig database. Health records were screened to identify prescribed rivaroxaban dose, presence or absence of renal impairment, patient characteristics, further dosing‐relevant diagnoses and co‐medication with antiplatelet drugs and non‐vitamin K oral anticoagulants (NOACs). Results We identified a total of 378 consecutive patients. In 282 cases (74.6%), rivaroxaban was prescribed in a standard dose and in 96 (25.4%) in a reduced dose. Out of 96 patients receiving a reduced dose, 50 (52.1%) did not meet labeling criteria for dose reduction. In uni‐ and multivariate regression analysis, estimated glomerular filtration rate (eGFR) (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.12‐0.95, P = .04) was the only independent predictor of rivaroxaban underdosage. Conclusions In clinical practice, rivaroxaban dosing is frequently incoherent with labeling. In this study, rivaroxaban was often administered underdosed. Potentially inappropriate dose reduction was significantly associated with eGFR, the same factor that is used as criterion for dose adjustment.

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Effectiveness and Safety of Direct Oral Anticoagulants Among Patients with Non-valvular Atrial Fibrillation and Multimorbidity

et al. 2022

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Introduction: In the USA, there is a steady rise of atrial fibrillation due to the aging population with increased morbidity. This study evaluated the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) among elderly patients with non-valvular atrial fibrillation (NVAF) and multimorbidity prescribed direct oral anticoagulants (DOACs). Methods: Using the CMS Medicare database, a retrospective observational study of adult patients with NVAF and multimorbidity who initiated apixaban, dabigatran, or rivaroxaban from January 1, 2012 to December 31, 2017 was conducted. High multimorbidity was classified as having C 6 comorbidities. Cox proportional hazard models were used to evaluate the hazard ratios of S/SE and MB among three 1:1 propensity score matched DOAC cohorts. All-cause healthcare costs were estimated using generalized linear models. Results: Overall 36% of the NVAF study population had high multimorbidity, forming three propensity score matched (PSM) cohorts: 12,511 apixaban-dabigatran, 60,287 apixabanrivaroxaban, and 12,567 dabigatran-rivaroxaban patients. Apixaban was associated with a lower risk of stroke/SE and MB when compared with dabigatran and rivaroxaban. Dabigatran had a lower risk of stroke/SE and a similar risk of MB when compared with rivaroxaban. Compared to rivaroxaban, apixaban patients incurred lower all-cause healthcare costs, and dabigatran patients incurred similar all-cause healthcare costs. Compared to dabigatran, apixaban patients incurred similar all-cause healthcare costs. Conclusion: Patients with NVAF and C 6 comorbid conditions had significantly different risks for stroke/SE and MB when comparing DOACs to DOACs, and different healthcare expenses. This study's results may be useful for evaluating the risk-benefit ratio of DOAC use in patients with NVAF and multimorbidity.

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Effect of Renal Function on Dosing of Non–Vitamin K Antagonist Direct Oral Anticoagulants Among Patients With Nonvalvular Atrial Fibrillation

Abstract: Inappropriate dosing occurred among patients with normal and insufficient renal function. The consideration of clinical factors beyond renal function is necessary to reduce bleeding risk associated with DOAC therapy.

Cited by 18 publications

References 13 publications

Incidence of direct oral anticoagulant use in patients with nonvalvular atrial fibrillation and characteristics of users in 6 European countries (2008–2015): A cross‐national drug utilization study

Incidence of direct oral anticoagulant use in patients with nonvalvular atrial fibrillation and characteristics of users in 6 European countries (2008–2015): A cross‐national drug utilization study

Initial rivaroxaban dosing in patients with atrial fibrillation

Effectiveness and Safety of Direct Oral Anticoagulants Among Patients with Non-valvular Atrial Fibrillation and Multimorbidity

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