scholarly journals How to handle the delayed or the missed dose of edoxaban in patients with non-valvular atrial fibrillation: model-informed remedial strategy

2021 ◽  
Author(s):  
Yi-wei Yin ◽  
Xiaoqin Liu ◽  
Jiaqin Gu ◽  
Ziran Li ◽  
Zheng Jiao
Keyword(s):  
Atrial Fibrillation ◽  
Monte Carlo ◽  
Delay Time ◽  
Factor Xa ◽  
Heart Rhythm ◽  
Total Deviation ◽  
Delay Duration ◽  
Half Dose ◽  
Dosing Regimens ◽  
Remedial Strategies

Aim: Edoxaban is a non-vitamin K antagonist oral anticoagulant (NOAC) widely used for long-term stroke prevention in patients with non-valvular atrial fibrillation (NVAF). Adherence to NOACs is unsatisfactory and decreases over time. The aim of this study was to explore appropriated remedial dosing regimens for non-adherent edoxaban-treated NVAF patients through the Monte Carlo simulation. Methods: Six proposed regimens were compared with the recommendations in the European Heart Rhythm Association (EHRA) guide regarding the trough total deviation time considering both edoxaban plasma concentration and inactive factor Xa activity. Monte Carlo simulations were performed using RxODE based on the published population pharmacokinetics/pharmacodynamics model. Results: The proposed remedial strategies were different from EHRA recommendations and were related to delay duration. The missed dose can be taken immediately if the delay time is within 11 h. When the delay period is between 12 and 19 h, a half dose followed by a regular dosing schedule is recommended. When the delay time exceeds 19 h, a full dose followed by a half dose is preferred compared to that recommended in the EHRA guide. Our proposed strategies resulted in a shorter total deviation time than EHRA guide. Conclusion: PK/PD modelling and simulation are effective in developing and evaluating the remedial strategies of edoxaban, which could help maximize its therapeutic effect.

scholarly journals Remedial dosing recommendation for delayed or missed rivaroxaban doses for patients with non-valvular atrial fibrillation based on Monte Carlo simulation

2020 ◽  
Author(s):  
Xiao-qin Liu ◽  
Yin-wei Yin ◽  
Chen-yu Wang ◽  
Zi-ran Li ◽  
Xiao Zhu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Factor Xa ◽  
Heart Rhythm ◽  
Population Pharmacokinetic ◽  
Dosing Regimen ◽  
Drug Concentrations ◽  
Simulation Based ◽  
Dosing Regimens

Background Rivaroxaban is a non-vitamin K oral anticoagulant used widely for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). During long-term anticoagulant therapy, delayed or missed doses are common. However, a lack of practical instructions on remedial methods has created a barrier for patients to maximise the benefit of their medications. This study aimed to explore appropriate remedial dosing regimens for rivaroxaban-treated patients with NVAF. Methods Monte Carlo simulation based on a previously established rivaroxaban population pharmacokinetic/pharmacodynamic model for patients with NVAF was employed to design remedial dosing regimens. Both the European Heart Rhythm Association (EHRA) recommendations and the model were used to establish remedial dosing regimens, which were assessed considering the on-therapy range of drug concentration, factor Xa activity, and prothrombin time under various scenarios of non-adherence. Results Recommendations of EHRA guide may not be optimal. Our findings suggested that a missed dose is taken immediately when the delay is less than or equal to 6 h; a half dose is advisable when the delay exceeds 6 h but is less than 4 h before the next dose. It is recommended to skip a dose when there are less than 4 h before the next dose. Age or renal function do not significantly influence the remedial dosing regimen. Conclusion A remedial dosing regimen based on model-based Monte Carlo simulation was systematically developed for rivaroxaban-treated patients with NVAF with poor adherence to quickly restore drug concentrations to the on-therapy range and to reduce the risk of bleeding and thromboembolism.

scholarly journals Evaluation of Apixaban for the Treatment of Nonvalvular Atrial Fibrillation With Regard to Dosing and Safety in a Community Hospital

2017 ◽  
Vol 33 (4) ◽  
pp. 140-145 ◽  
Author(s):  
Katie B. Tellor ◽  
Michelle Wang ◽  
Melissa S. Green ◽  
Anastasia L. Armbruster
Keyword(s):  
Atrial Fibrillation ◽  
Community Hospital ◽  
Factor Xa ◽  
Retrospective Chart Review ◽  
Prescribing Patterns ◽  
Minor Bleeding ◽  
Nonvalvular Atrial Fibrillation ◽  
Hospital Design ◽  
Patient Demographics ◽  
Dosing Regimens

Background: Apixaban, a direct factor Xa inhibitor, is approved by the US Food and Drug Administration (FDA) for prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. Apixaban’s compelling safety and efficacy data, combined with minimal laboratory monitoring, make it an attractive anticoagulant. Objectives: To characterize and evaluate the dosing and safety of apixaban for the treatment of nonvalvular atrial fibrillation at a community hospital. Design/Patients: A retrospective chart review evaluated patients ≥18 years of age who received at least 2 consecutive doses of apixaban from January 1, 2013 to June 30, 2016. Patients with multiple admissions were evaluated for each hospitalization. Patients were excluded if height, weight, or serum creatinine was not documented during hospital admission. Patients who received apixaban for the treatment or prophylaxis of venous thromboembolism were excluded. Prescribing patterns were characterized based on FDA-approved dosing regimens and patient demographics. Safety outcomes included incidences of major, clinically relevant nonmajor, and minor bleeding. Results: Of the 707 patients evaluated, 82% received an FDA-approved apixaban regimen. Of the 127 patients (18%) who received an unapproved regimen, 5.5% (7 patients) received an unapproved frequency and 94.5% (120 patients) received an unapproved dose. The majority (98 patients, 81.7%) were underdosed. Composite bleeding rates were 2.7%, with 1.8% major bleeds, 0.7% clinically relevant nonmajor bleeds, and 0.1% minor bleeds. Conclusions: The use of apixaban must be monitored in order to ensure FDA-approved dosing regimens are being prescribed and patients are not being underdosed.

scholarly journals Large extracellular vesicles in the left atrial appendage in patients with atrial fibrillation—the missing link?

2021 ◽  
Author(s):  
Andreas Zietzer ◽  
Baravan Al-Kassou ◽  
Paul Jamme ◽  
Verena Rolfes ◽  
Eva Steffen ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Extracellular Vesicles ◽  
Left Atrial ◽  
Left Atrial Appendage ◽  
Thrombus Formation ◽  
Flow Cytometric Analysis ◽  
Heart Rhythm ◽  
Atrial Appendage ◽  
Peripheral Embolization

AbstractAtrial fibrillation (AF) is the most frequent arrhythmic disease in humans, which leads to thrombus formation in the left atrial appendage and stroke through peripheral embolization. Depending on their origin, large extracellular vesicles (lEVs) can exert pro-coagulant functions. In the present study, we investigated how different types of AF influence the levels of large EV subtypes in three distinct atrial localizations. Blood samples were collected from the right and left atrium and the left atrial appendage of 58 patients. 49% of the patients had permanent AF, 34% had non-permanent AF, and 17% had no history of AF. Flow cytometric analysis of the origin of the lEVs showed that the proportion of platelet-derived lEVs in the left atrial appendage was significantly higher in permanent AF patients compared to non-permanent AF. When we grouped patients according to their current heart rhythm, we also detected significantly higher levels of platelet-derived lEVs in the left atrial appendage (LAA) in patients with atrial fibrillation. In vitro studies revealed, that platelet activation with lipopolysaccharide (LPS) leads to higher levels of miR-222-3p and miR-223-3p in platelet-derived lEVs. Treatment with lEVs from LPS- or thrombin-activated platelets reduces the migration of endothelial cells in vitro. These results suggest that permanent atrial fibrillation is associated with increased levels of platelet-derived lEVs in the LAA, which are potentially involved in LAA thrombus formation.

scholarly journals Kardia Mobile and ISTEL HR applicability in clinical practice: A comparison of Kardia Mobile, ISTEL HR and standard 12-lead electrocardiogram records in 98 consecutive patients of a tertiary cardiovascular care centre

2021 ◽  
Author(s):  
Bartosz Krzowski ◽  
Kamila Skoczylas ◽  
Gabriela Osak ◽  
Natalia Żurawska ◽  
Michał Peller ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Practice ◽  
Cardiovascular Diseases ◽  
Sinus Rhythm ◽  
Sensitivity And Specificity ◽  
Heart Rhythm ◽  
Everyday Practice ◽  
Portable Devices ◽  
Care Centre ◽  
Cardiovascular Care

Abstract Aims Mobile, portable ECG-recorders allow the assessment of heart rhythm in out-of-hospital conditions and may prove useful for monitoring patients with cardiovascular diseases. However, the effectiveness of these portable devices has not been tested in everyday practice. Methods and results A group of 98 consecutive cardiology patients (62 males [63%], mean age 69 ± 12.9 years) were included in an academic care centre. For each patient, a standard 12-lead electrocardiogram (SE), as well as a Kardia Mobile 6L (KM) and Istel (IS) HR-2000 ECG were performed. Two groups of experienced physycians analyzed obtained recordings. After analyzing ECG tracings from SE, KM, and IS, quality was marked as good in 82%, 80%, and 72% of patients, respectively (p < 0.001). There were no significant differences between devices in terms of detecting sinus rhythm (SE [60%, n = 59], KM [58%, n = 56], and IS [61%, n = 60]; SE vs KM p = 0.53; SE vs IS p = 0.76) and atrial fibrillation (SE [22%, n = 22], KM [22%, n = 21], and IS [18%, n = 18]; (SE vs KM p = 0.65; SE vs IS = 0.1). KM had a sensitivity of 88.1% and a specificity of 89.7% for diagnosing sinus rhythm. IS showed 91.5% and 84.6% sensitivity and specificity, respectively. The sensitivity of KM in detecting atrial fibrillation was higher than IS (86.4% vs. 77.3%), but their specificity was comparable (97.4% vs. 98.7%). Conclusion Novel, portable devices are useful in showing sinus rhythm and detecting atrial fibrillation in clinical practice. However, ECG measurements concerning conduction and repolarisation should be clarified with a standard 12-lead electrocardiogram.

Long-term outcomes of Japan-specific dosage of rivaroxaban in high-risk patients with non-valvular atrial fibrillation: analysis from the XAPASS

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Ikeda ◽  
S Ogawa ◽  
T Kitazono ◽  
J Nakagawara ◽  
K Minematsu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
High Risk ◽  
Major Bleeding ◽  
Factor Xa ◽  
Incidence Rates ◽  
Funding Source ◽  
High Risk Patients ◽  
Reduced Dose ◽  
Risk Patients

Abstract Background XAPASS is a real-world, prospective, single-arm, observational study conducted as a post-marketing surveillance mandated by the health authority in Japan. Nowadays, direct oral anticoagulant therapy using factor Xa or thrombin inhibitor has been the standard of care for patients with non-valvular atrial fibrillation (NVAF) to prevent ischemic stroke. However, the clinical impact of reduced dosage (approved dose of 15 or 10 mg once daily in Japan is relatively reduced compared to global dosage) factor Xa inhibitor rivaroxaban in high-risk patients remains unclear. Purpose The present sub-analysis of XAPASS was carried out to assess long-term safety and effectiveness of reduced-dose rivaroxaban in high-risk NVAF patients for bleeding and thromboembolism. Methods All patients with NVAF who were newly started on rivaroxaban were eligible for surveillance. The principal safety outcome was a composite of major and non-major bleeding events, and the primary effectiveness outcome was a composite of ischaemic stroke, haemorrhagic stroke, non-central nervous system systemic embolism (non-CNS SE), and myocardial infarction (MI). In this present sub-analysis, high-risk patients were defined as those who had two of the following three risk factors: elderly (≥75 years old), low body weight (≤50 kg), and renal impairment (CrCl <50 mL/min). Results In total, 11,308 patients were enrolled between April 2012 and June 2014 from 1,419 hospitals, and overall data were analysed from 10,664 patients from whom data were collected. Among them, 3,694 patients matched the criteria for the high-risk patients defined in this sub-analysis, and 6,970 patients did not match the criteria (non-high-risk patients). The mean treatment duration was 791±673 days in the high-risk patients and 944±709 days in the non-high-risk patients. Mean patient age was 80.9±5.5 years and 69.0±9.0 years at baseline, respectively. Mean CHADS2 score was 2.8 and 1.8, and CHA2DS2-VASc score was 4.4 and 2.9, respectively. The rates of CHADS2 component comorbidities were lower in the non-high-risk patients except for diabetes mellitus. The incidence rates of any bleeding, major bleeding, and the primary effectiveness outcomes were 4.8, 1.6, and 2.1%/patient-year in the high-risk patients. The incidence rates of these clinical events in the non-high-risk patients were 3.3, 0.9, and 1.0%/patient-year, respectively. Conclusions Incidence rates of long-term bleeding and thromboembolism were higher in the high-risk patients than in the non-high-risk patients. However, the rates of these outcomes using the Japan-specific reduced dose were not so high. Furthermore, the balance between safety and effectiveness outcomes was within an acceptable range. The present study provides useful information for physicians to stratify high-risk patients using the reduced dose in daily clinical practice. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Bayer Yakuhin Ltd.

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