Dataset Information

Effectiveness and Safety of Off-label Dosing of Non-vitamin K Antagonist Anticoagulant for Atrial Fibrillation in Asian Patients.

ABSTRACT: Non-vitamin K antagonist anticoagulants (NOACs) have been used to prevent thromboembolism in patients with atrial fibrillation (AF) and shown favorable clinical outcomes compared with warfarin. However, off-label use of NOACs is frequent in practice, and its clinical results are inconsistent. Furthermore, the quality of anticoagulation available with warfarin is often suboptimal and even inaccurate in real-world data. We have therefore compared the effectiveness and safety of off-label use of NOACs with those of warfarin whose anticoagulant intensity was accurately estimated. We retrospectively analyzed data from 2,659 and 3,733 AF patients at a tertiary referral center who were prescribed warfarin and NOACs, respectively, between 2013 and 2018. NOACs were used at off-label doses in 27% of the NOAC patients. After adjusting for significant covariates, underdosed NOAC (off-label use of the reduced dose) was associated with a 2.5-times increased risk of thromboembolism compared with warfarin, and overdosed NOAC (off-label use of the standard dose) showed no significant difference in either thromboembolism or major bleeding compared with warfarin. Well-controlled warfarin (TTR???60%) reduced both thromboembolism and bleeding events. In conclusion, the effectiveness of NOACs was decreased by off-label use of the reduced dose.

SUBMITTER: Lee KN

PROVIDER: S-EPMC7000392 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Effectiveness and Safety of Off-label Dosing of Non-vitamin K Antagonist Anticoagulant for Atrial Fibrillation in Asian Patients.

Lee Kwang-No KN Choi Jong-Il JI Boo Ki Yung KY Kim Do Young DY Kim Yun Gi YG Oh Suk-Kyu SK Baek Yong-Soo YS Lee Dae In DI Roh Seung-Young SY Shim Jaemin J Kim Jin Seok JS Kim Young-Hoon YH

Scientific reports 20200204 1

Non-vitamin K antagonist anticoagulants (NOACs) have been used to prevent thromboembolism in patients with atrial fibrillation (AF) and shown favorable clinical outcomes compared with warfarin. However, off-label use of NOACs is frequent in practice, and its clinical results are inconsistent. Furthermore, the quality of anticoagulation available with warfarin is often suboptimal and even inaccurate in real-world data. We have therefore compared the effectiveness and safety of off-label use of NO ...[more]

PMID: 32019993

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Project description:BackgroundTo clarify the appropriate initial dosage of heparin during radiofrequency catheter ablation (RFCA) in patients with atrial fibrillation (AF) receiving uninterrupted nonvitamin K antagonist oral anticoagulant (NOAC) treatment.MethodsA total of 187 consecutive AF patients who underwent their first RFCA in our center were included. In the warfarin group (WG), an initial heparin dose of 100 U/kg was administered (control group: n = 38). The patients who were on NOACs were randomly divided into 3 NOAC groups (NG: n = 149), NG110, NG120, and NG130, and were administered initial heparin doses of 110 U/kg, 120 U/kg, and 130 U/kg, respectively. During RFCA, the activated clotting time (ACT) was measured every 15 min, and the target ACT was maintained at 250-350 s by intermittent heparin infusion. The baseline ACT and ACTs at each 15-min interval, the average percentage of measurements at the target ACT, and the incidence of periprocedural bleeding and thromboembolic complications were recorded and analyzed.ResultsThere was no significant difference in sex, age, weight, or baseline ACT among the four groups. The 15 min-ACT, 30 min-ACT, and 45 min-ACT were significantly longer in the WG than in NG110 and NG120. However, no significant difference in 60 min-ACT or 75 min-ACT was detected. The average percentages of measurements at the target ACT in NG120 (82.2 ± 23.6%) and NG130 (84.8 ± 23.7%) were remarkably higher than those in the WG (63.4 ± 36.2%, p = 0.007, 0.003, respectively). These differences were independent of the type of NOAC. The proportion of ACTs in 300-350 s in NG130 was higher than in WG (32.4 ± 31.8 vs. 34.7 ± 30.6, p = 0.735). Severe periprocedural thromboembolic and bleeding complications were not observed.ConclusionsFor patients with AF receiving uninterrupted NOAC treatment who underwent RFCA, an initial heparin dosage of 120 U/kg or 130 U/kg can provide an adequate intraprocedural anticoagulant effect, and 130 U/kg allowed ACT to reach the target earlier.Trial registrationRegistration number: ChiCTR1800016491, First Registration Date: 04/06/2018 (Chinese Clinical Trial Registry http://www.chictr.org.cn/index.aspx ).

Project description:AimsLimited real-world data show that rivaroxaban following dosage criteria from either ROCKET AF [20 mg/day or 15 mg/day if creatinine clearance (CrCl) < 50 mL/min] or J-ROCKET AF (15 mg/day or 10 mg/day if CrCl < 50 mL/min) is associated with comparable risks of thromboembolism and bleeding with each other in patients with non-valvular atrial fibrillation (NVAF). We are aimed to study whether these observations differ between Asian and non-Asian subjects.Methods and resultsA systematic review and meta-analysis with random effects was conducted to estimate the aggregate hazard ratio (HR) and 95% confidence interval (CI) using PubMed and MEDLINE databases from 8 September 2011 to 31 December 2022 searched for adjusted observational studies that reported relevant clinical outcomes of NVAF patients receiving rivaroxaban 10 mg/day if CrCl > 50 mL/min, on-label dose rivaroxaban eligible for ROCKET AF or J-ROCKET AF, and rivaroxaban 20 mg/day if CrCl < 50 mL/min. Effectiveness and safety endpoints were compared between ROCKET AF and J-ROCKET AF dosing regimen in Asian and non-Asian subjects, separately. Also, risks of events of rivaroxaban 10 mg/day despite of CrCl > 50 mL/min and rivaroxaban 20 mg/day despite of CrCl < 50 mL/min were compared to that of 'ROCKET AF/J-ROCKET AF dosing'. Sensitivity analyses were performed by sequential elimination of each study from the pool. The meta-regression analysis was performed to explore the influence of potential factors on the effectiveness and safety outcomes. Eighteen studies involving 67 571 Asian and 54 882 non-Asian patients were included. Rivaroxaban following J-ROCKET AF criteria was associated with comparable risks of thromboembolism in the Asian subgroup, whereas rivaroxaban following J-ROCKET AF criteria was associated with higher risks of all-cause mortality (HR:1.30; 95% CI:1.05-1.60) compared with that of ROCKET AF criteria in the non-Asian population. There were no differences in risks of major bleeding between rivaroxaban following J-ROCKET AF vs. ROCKET AF criteria either in the Asian or non-Asian population. The use of rivaroxaban 10 mg despite of CrCl > 50 mL/min was associated with a higher risk of thromboembolism (HR:1.64; 95% CI:1.28-2.11) but lower risk of major bleeding (HR:0.72; 95% CI:0.57-0.90) compared with eligible dosage criteria. The use of rivaroxaban 20 mg despite of CrCl < 50 mL/min was associated with worse clinical outcomes in the risks of thromboembolism (HR:1.32; 95% CI:1.09-1.59), mortality (HR:1.33; 95% CI:1.10-1.59), and major bleeding (HR:1.26; 95% CI:1.03-1.53) compared with eligible dosage criteria. The pooled results were generally in line with the primary effectiveness and safety outcomes by removing a single study at one time. Meta-regression analyses failed to detect the bias in most potential patient characteristics associated with the clinical outcomes.ConclusionRivaroxaban dosing regimen following J-ROCKET criteria may serve as an alternative to ROCKET AF criteria for the Asian population with NVAF, whereas the dosing regimen following ROCKET AF criteria was more favourable for the non-Asian population. The use of rivaroxaban 10 mg despite of CrCl > 50 mL/min was associated with a higher risk of thromboembolism but a lower risk of major bleeding, while use of rivaroxaban 20 mg despite of CrCl < 50 mL/min was associated with worse outcome in most clinical events.

Project description:Introduction:Clinical guidelines recommend non-vitamin K antagonist oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) for stroke prevention in most patients with atrial fibrillation (AF). Frail elderly were under-represented in the landmark NOAC-trials, leaving a knowledge gap on the optimal anticoagulant management (VKA or NOAC) in this increasing population. The aim of the Frail-AF (FRAIL-AF) study is to assess whether switching from international normalised ratio (INR)-guided VKA-management to a NOAC-based treatment strategy compared with continuing VKA-management is safe in frail elderly patients with AF.Methods and analysis:The FRAIL-AF study is a pragmatic, multicentre, open-label, randomised controlled clinical trial. Frail elderly (age ≥75 years plus a Groningen Frailty Indicator score ≥3) who receive VKA-treatment for AF in the absence of a mechanical heart valve or severe mitral valve stenosis will be randomised to switch to a NOAC-based treatment strategy or to continue INR-guided VKA-management. Patients with severe renal impairment (estimated glomerular filtration rate <30 mL/min/1.73 m2) will be excluded from randomisation. Based on existing trial evidence in non-frail patients, we will aim to explore whether NOAC-treatment is superior to VKA-therapy in reducing major or clinically relevant non-major bleeding events. Secondary outcomes include minor bleeding, the composite of ischaemic and haemorrhagic stroke, health-related quality of life and cost-effectiveness. The follow-up period for all subjects is 12 months.Ethics and dissemination:The protocol was approved by the Medical Research Ethics Committee of the University Medical Center Utrecht, the Netherlands and by the Central Committee on Research Involving Human Subjects, the Netherlands. All patients are asked written informed consent. Results are expected in 2022 and will be disseminated through peer-reviewed journals as well as presentations at national and international conferences.Trial registration number:EudraCT: 2017-000393-11; The Netherlands Trial Registry: 6721 (FRAIL-AF study).

Project description:AimsUsing Scandinavian population-based registries, we assessed risk of stroke/systemic embolism (SE) and bleeding with non-vitamin K antagonist oral anticoagulants compared with warfarin in anticoagulation-naïve patients with atrial fibrillation (AF).Methods and resultsThis historical cohort study included 219 545 AF patients [median age 74 years; 43% women; mean CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischaemic attack, vascular disease, age 65-74 years, sex category) score 3.3] initiating apixaban, dabigatran, rivaroxaban, or warfarin in Denmark, Norway, and Sweden (1 January 2013 to 31 December 2016). The primary endpoints were stroke/SE and major bleeding. The median follow-up times were 9.7 (3.9-21.5) months for stroke/SE and 9.6 (3.8-21.3) months for bleeding. Apixaban and warfarin initiators were older and had higher CHA2DS2-VASc scores compared with dabigatran and rivaroxaban initiators. After 1:1 propensity score matching, three cohorts were created: apixaban-warfarin (n = 111 162), dabigatran-warfarin (n = 56 856), and rivaroxaban-warfarin (n = 61 198). Adjusted hazard ratios (HRs) were estimated using a Cox regression. For stroke/SE, adjusted HRs against warfarin were 0.96 [95% confidence interval (CI): 0.87-1.06] for apixaban, 0.89 (95% CI: 0.80-1.00) for dabigatran, and 1.03 (95% CI: 0.92-1.14) for rivaroxaban. For major bleeding, the HRs against warfarin were 0.73 (95% CI: 0.67-0.78) for apixaban, 0.89 (95% CI: 0.82-0.97) for dabigatran, and 1.15 (95% CI: 1.07-1.25) for rivaroxaban. The results in the dabigatran cohort did not hold in all dose-defined subgroups.ConclusionIn this large Scandinavian study among AF patients initiating oral anticoagulation, those initiating dabigatran, apixaban, and rivaroxaban had similar rates of stroke/SE to patients initiating warfarin. Rates of major bleeding were lower with apixaban and dabigatran and higher with rivaroxaban, each compared with warfarin.

Dataset Information

Effectiveness and Safety of Off-label Dosing of Non-vitamin K Antagonist Anticoagulant for Atrial Fibrillation in Asian Patients.

Publications

Effectiveness and Safety of Off-label Dosing of Non-vitamin K Antagonist Anticoagulant for Atrial Fibrillation in Asian Patients.

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