Appropriateness of non-vitamin K antagonist oral anticoagulant dose in patients with atrial fibrillation in Israel: A population-based study

Ellis, Martin; Dotan, Sari Greenberg; Hammerman, Ariel; Battat, Erez; Derazne, Estela; Avnery, Orly

doi:10.1016/j.thromres.2018.07.024

Cited by 7 publications

(10 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Potential underdosing of NOACs has been reported in moderate-to-large studies from the USA,10 11 as well as in smaller studies from Europe, North America12–14 and Israel,15 with findings indicative of variation in the level of inappropriate NOAC dosing between countries. Using data from 7925 patients with AF in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II (ORBIT-AF-II) registry, Steinberg et al ,10 reported that 57% (734/1289) of patients prescribed a reduced dose NOAC did not fulfil the Food and Drug Administration’s (FDAs) recommended criteria for dose reduction.…”

Section: Discussionmentioning

confidence: 99%

“…Decisions to prescribe standard or reduced dose NOACs are made on the basis of specific considerations such as age, weight, renal function and use of specific concomitant medications. Descriptive data show that a high proportion of patients with AF initiating anticoagulant therapy with a NOAC are prescribed a reduced dose,4 8–10 particularly in Europe,8 9 with evidence to suggest that many of these patients do not satisfy the necessary dose reduction criteria as specified on the drug labels 10–15. In Europe, studies describing the appropriate dosing of prescribed NOACs have been conducted in smaller cohorts8 12–14 and/or limited to a particular drug,8 14 and we are unaware of any conducted in patients with non-valvular atrial fibrillation (NVAF) in the UK.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Appropriateness of initial dose of non-vitamin K antagonist oral anticoagulants in patients with non-valvular atrial fibrillation in the UK

et al. 2019

View full text Add to dashboard Cite

ObjectiveTo evaluate the appropriateness of the initial prescribed daily dose of non-vitamin K antagonist oral anticoagulants (NOACs) according to label in patients with non-valvular atrial fibrillation (NVAF) in the UK.DesignPopulation-based cross-sectional study.SettingUK primary care.Population30 467 patients with NVAF and a first prescription for apixaban, dabigatran or rivaroxaban between January 2011 and December 2016.Main outcome measuresPercentage of patients prescribed a NOAC dose according to the European Union (EU) labels (appropriately dosed), and not according to the EU labels (inappropriately dosed—including both underdosed and overdosed patients); percentage of patients prescribed an initial NOAC dose according to renal function status.ResultsA total of 15 252 (50.1%) patients started NOAC therapy on rivaroxaban, 10 834 (35.6%) on apixaban and 4381 (14.4%) on dabigatran. Among patients starting NOAC therapy on rivaroxaban, 17.3% were eligible to receive a reduced dose compared with 12.8% of patients starting on apixaban and 53.8% of patients starting on dabigatran. The majority of patients were prescribed an appropriate dose according to the EU labels: apixaban 74.9 %, dabigatran, 74.4%; rivaroxaban, 84.2%. Underdosing occurred in 21.6% (apixaban), 8.7% (dabigatran), 9.1% (rivaroxaban). Overdosing was more frequent for dabigatran (16.9%) than for rivaroxaban (6.6%) or apixaban (3.5%). There was a trend towards dose reduction with increasing renal impairment. Among patients with severe renal impairment, the majority received a reduced dose NOAC: apixaban, 91.1%, dabigatran, 80.0%, rivaroxaban, 83.0%.ConclusionBetween 2011 and 2016, the majority of patients starting NOAC therapy in UK primary care were prescribed a daily dose in line with the approved EU drug label. Underdosing was more than twice as common among patients starting on apixaban than those starting on dabigatran or rivaroxaban. Research into the patient characteristics that may influence inappropriate underdosing of NOACs in UK primary care is warranted.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Appropriateness of initial dose of non-vitamin K antagonist oral anticoagulants in patients with non-valvular atrial fibrillation in the UK

et al. 2019

View full text Add to dashboard Cite

show abstract

“…According to the clinical guidelines ( Lip et al, 2018 ; Steffel et al, 2018 ; January et al, 2019 ), dose adjustment of DOAC should be made based on patient’s characteristics, for example, age, renal function, and body weight. Although the criteria of dose adjustment of each DOAC have been well established, inappropriate off-label dose of DOACs is not uncommon ( Nielsen et al, 2017 ; Ellis et al, 2018 ; Staerk et al, 2018 ). In the ORBIT-AF II registry, almost 1 in 8 patients received DOAC doses inconsistent with labeling ( Steinberg et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Real-World Prevalence of Direct Oral Anticoagulant Off-Label Doses in Atrial Fibrillation: An Epidemiological Meta-Analysis

et al. 2021

View full text Add to dashboard Cite

Background: The use of direct oral anticoagulant (DOAC) off-label doses in atrial fibrillation (AF) patients may result in poor clinical outcomes. However, the true prevalence remains scarce. This study aims at estimating the prevalence of DOAC off-label doses in AF patients.Methods: Databases of MEDLINE, EMBASE, and COCHRANE were searched from inception through February 2020 for real-world studies that reported the off-label definition and prevalence data of AF patients using DOACs. The primacy outcomes were the overall prevalence of DOAC off-label doses and the corresponding underdose and overdose. The random-effects model was used for data synthesis. Variations on individual DOAC and different regions were examined by subgroup analyses.Results: A total of 23 studies involving 162,474 AF patients were finally included. The overall prevalence of DOAC off-label doses was 24% (95% CI, 19–28%), with 18% for dabigatran, 27% for rivaroxaban, 24% for apixaban, and 26% for edoxaban. The prevalence of underdosed DOACs was 20% (95% CI, 16–24%) with significant difference among individual anticoagulants (13% for dabigatran, 22% for rivaroxaban, 22% for apixaban, and 18% for edoxaban; Pinteraction=0.02). The prevalence of overdosed DOACs was 5% (95% CI, 3–7%), with the lowest prevalence observed in apixaban (2%). Subgroup analyses by regions demonstrated that the prevalence of DOAC off-label doses was higher in Asia (32%) than in North America (14%) and in Europe (22%), with underdose being predominant. Regardless of different regions, the prevalence of overdose was relatively low (4–6%).Conclusion: This study provides an estimation of DOAC off-label doses in the real-world setting. The prevalence rate of DOAC off-label doses in AF patients was relatively high, with underdose being predominant. Clinicians in Asia preferred to prescribe underdose of DOACs to AF patients. More evidence about the appropriateness of DOAC off-label doses in AF patients is urgently needed. Education programs concerning the appropriate prescription of DOACs within the drug labels and accepted guidelines are necessary to DOAC prescribers to ensure the safety and effectiveness of anticoagulation therapy for patients with AF.

show abstract

“…Use of lower doses has been reported inappropriate, that is, inconsistent with drug labeling, in up to half of the patients in some papers [16,21,22], while in a lower proportion in others [23,24].…”

Section: Discussionmentioning

confidence: 99%

Starting dose and dose adjustment of Non-vitamin K antagonist oral anticoagulation agents in a nationwide cohort of patients with atrial fibrillation

Gozzo

Lenarda²,

Mammarella

et al. 2020

Preprint

View full text Add to dashboard Cite

Purpose This study aims to provide real-world data about starting-dose of NOACs and dose- adjustment in patients with AF. In fact, even if new oral anticoagulation agents (NOACs) have a predictable effect without need for regular monitoring, dose-adjustments should be performed according to the summary of product information and international guidelines. Methods We employed the Italian Medicines Agency monitoring registries comprising data on a nationwide cohort of patients with AF treated with NOACs from 2013 to 2018. Logistic regression analysis was used to evaluate the determinants of dosage choice. Results During the reference period, treatment was commenced for 866539 patients. Forty-five percent of the first prescriptions were dispensed at a reduced-dose (dabigatran 60.3%, edoxaban 45.2%, apixaban 40.9%, rivaroxaban 37.4%). The prescription of reduced-dose was associated with older age, renal disease, bleeding risk and the concomitant use of drugs predisposing to bleeding, but not with CHA₂DS₂-VASc and HAS-BLED. A relative reduction of the proportion of patients treated with low-dosages was evident overtime for dabigatran and rivaroxaban; whereas prescription of low-dose apixaban and edoxaban increased progressively among elderly patients. Conclusions Evidence based on real-world data shows a high frequency of low-dose prescriptions of NOACs in AF patients. Except for older age, renal disease, bleeding risk and the concomitant use of drugs predisposing to bleeding, other factors that may determine the choice of reduced-dose could not be ascertained. There may be potential under-treatment of AF patients, but further evaluation is warranted.

show abstract

Appropriateness of non-vitamin K antagonist oral anticoagulant dose in patients with atrial fibrillation in Israel: A population-based study

Cited by 7 publications

References 9 publications

Appropriateness of initial dose of non-vitamin K antagonist oral anticoagulants in patients with non-valvular atrial fibrillation in the UK

Appropriateness of initial dose of non-vitamin K antagonist oral anticoagulants in patients with non-valvular atrial fibrillation in the UK

Real-World Prevalence of Direct Oral Anticoagulant Off-Label Doses in Atrial Fibrillation: An Epidemiological Meta-Analysis

Starting dose and dose adjustment of Non-vitamin K antagonist oral anticoagulation agents in a nationwide cohort of patients with atrial fibrillation

Contact Info

Product

Resources

About