Plasma levels of direct oral anticoagulants in atrial fibrillation patients at the time of embolic stroke: a pilot prospective multicenter study

Vladimir, Nosal; Petrovičová, Andrea; Škorňová, Ingrid; Bolek, Tomáš; Dluha, Jana; Stančiaková, Lucia; Sivák, Štefan; Babalova, Lucia; Hajaš, Gabriel; Staško, Ján; Kubisz, Peter; Kurča, Egon; Samoš, Matej; Mokáň, Marián

doi:10.1007/s00228-022-03280-8

Cited by 14 publications

(23 citation statements)

References 18 publications

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“…Rivaroxaban exposure has been associated with clinical outcomes and may aid in predicting the benefit-risk profile [13,16]. Peak Anti-Xa concentrations have been linked to bleeding complications [8][9][10], whereas trough concentrations have been related to the occurrence of thromboembolic events [11,12].…”

Section: Discussionmentioning

confidence: 99%

“…Studies have shown that individuals with AF who had a higher Anti-Xa levels of rivaroxaban measured at peak concentration reported more bleeding complications following treatment [8][9][10]. In addition, a previous study showed an elevated risk of thrombotic events in patients with low Anti-Xa level measured at trough concentration [11,12]. Therefore, a precise dosage of rivaroxaban would be required to provide optimum exposure.…”

Section: Introductionmentioning

confidence: 99%

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Population Pharmacokinetics and Dose Optimization Based on Renal Function of Rivaroxaban in Thai Patients with Non-Valvular Atrial Fibrillation

et al. 2022

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Low-dose rivaroxaban has been used in Asian patients with direct oral anticoagulants (DOACs) eligible for atrial fibrillation (AF). However, there are few pharmacokinetic (PK) data in Thai patients to support precise dosing. This study aimed to develop a population PK model and determine the optimal rivaroxaban doses in Thai patients. A total of 240 Anti-Xa levels of rivaroxaban from 60 Thai patients were analyzed. A population PK model was established using the nonlinear mixed-effect modeling approach. Monte Carlo simulations were used to predict drug exposures at a steady state for various dosages. Proportions of patients having rivaroxaban exposure within typical exposure ranges were determined. A one-compartment model with first-order absorption best described the data. Creatinine clearance (CrCl) and body weight significantly affected CL/F and V/F, respectively. Regardless of body weight, a higher proportion of patients with CrCl < 50 mL/min receiving the 10-mg once-daily dose had rivaroxaban exposures within the typical exposure ranges. In contrast, a higher proportion of patients with CrCl ≥ 50 mL/min receiving the 15-mg once-daily dose had rivaroxaban exposures within the typical exposure ranges. The study’s findings suggested that low-dose rivaroxaban would be better suited for Thai patients and suggested adjusting the medication’s dose in accordance with renal function.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Population Pharmacokinetics and Dose Optimization Based on Renal Function of Rivaroxaban in Thai Patients with Non-Valvular Atrial Fibrillation

et al. 2022

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“…Acute stroke decision‐making requires careful consideration of risks and benefits, yet we must remain cognisant that mild strokes can result in significant disability, with ongoing trials exploring the benefit of thrombolysis in mild strokes 14,15 . Second, there is increasing evidence to suggest an association between low DOAC levels and increased stroke incidence and severity 16,17 . Third, a DOAC level outside of the expected ‘on‐therapy’ range should prompt the clinician to search for an explanation, most commonly medication non‐adherence (30% in our cohort).…”

Section: Discussionmentioning

confidence: 99%

Trends in direct oral anticoagulant use in patients presenting with acute stroke

Teow

Tan

Frost

et al. 2022

Internal Medicine Journal

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Acute ischaemic strokes occur despite the use of direct oral anticoagulants (DOACs). A retrospective review was conducted at a high‐volume primary stroke centre over a 3‐year period to assess the acute management of stroke presentations in patients prescribed DOACs. During the time period of the study, 103 of 195 anticoagulated stroke patients presented within the timeframe for thrombolysis and only 15 patients had DOAC plasma level assays performed. Of these 103, 5 received thrombolysis; however, DOAC level was not a factor in these cases.

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“…Second, Testa et al reported in their studies [ 5 , 6 ] that bleeding during DOAC therapy was more frequent in AF patients with high peak drug levels [ 5 ] and thrombotic events developed in individuals who had low baseline trough drug levels [ 6 ]. Third, looking at the drug levels at the time of the bleeding or ischemic event [ 7 , 8 ], patients with a DOAC therapy-related bleeding had significantly higher and patients with a stroke despite taking DOAC had significantly lower DOAC levels at the time of this event compared to individuals tolerating the DOAC therapy without any adverse events. Finally, in a recent observational study performed by Siedler et al [ 9 ] patients who suffered from early ischemic stroke recurrence despite the use of DOAC had low DOAC plasma levels (this was demonstrated for apixaban and dabigatran after propensity score matching).…”

Section: In-optimal Doac Levels and The Risk Of Future Adverse Eventsmentioning

confidence: 99%

“…In our previous studies, which aimed to establish DOAC plasma levels at the time of an adverse event, in dabigatran-treated patients with bleeding, dabigatran levels of 261.4 ± 163.7 ng/mL were determined on average [ 7 ]. In patients with embolic stroke, average dabigatran plasma levels of 40.7 ± 36.9 ng/mL were found [ 8 ]. This observation probably supports the upper reference range of 210 ng/mL in terms of safety, but questions the lower reference range of 28 ng/mL in terms of efficacy.…”

Section: Optimal Doac Plasma Levels For Long-term Anticoagulationmentioning

confidence: 99%

Tailored Direct Oral Anticoagulation in Patients with Atrial Fibrillation: The Future of Oral Anticoagulation?

Samoš

Bolek

Stančiaková

et al. 2022

JCM

Self Cite

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Direct oral anticoagulants (DOAC) are currently the drug of choice for drug prevention of stroke or systemic embolism in patients with atrial fibrillation (AF). However, repeated ischemic stroke or systemic embolism and bleeding while on DOAC is still a challenging clinical phenomenon in the management of future long-term anticoagulation. It is not known whether tailoring the DOAC therapy to achieve optimal therapeutic drug levels could improve the clinical course of DOAC therapy. To be able to tailor the therapy, it is necessary to have a valid laboratory method for DOAC level assessment, to be aware of factors influencing DOAC levels and to have clinical options to tailor the treatment. Furthermore, the data regarding clinical efficacy/safety of tailored DOAC regimes are still lacking. This article reviews the current data on tailored direct oral anticoagulation in patients with AF.

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Plasma levels of direct oral anticoagulants in atrial fibrillation patients at the time of embolic stroke: a pilot prospective multicenter study

Cited by 14 publications

References 18 publications

Population Pharmacokinetics and Dose Optimization Based on Renal Function of Rivaroxaban in Thai Patients with Non-Valvular Atrial Fibrillation

Population Pharmacokinetics and Dose Optimization Based on Renal Function of Rivaroxaban in Thai Patients with Non-Valvular Atrial Fibrillation

Trends in direct oral anticoagulant use in patients presenting with acute stroke

Tailored Direct Oral Anticoagulation in Patients with Atrial Fibrillation: The Future of Oral Anticoagulation?

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