Personalized approach for direct oral anticoagulant prescription: from theory to practice

Q: What is the clinical evidence from this study?

Study design: Review. Population: Atrial fibrillation. Intervention: Direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, edoxaban) and pharmacogenetic/pharmacokinetic testing.

Q: What does this research mean for the field?

Direct oral anticoagulant pharmacokinetics vary substantially by renal function, age, drug interactions, and specific genetic polymorphisms, though clinical outcome data supporting personalization remain largely limited to dabigatran. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

А. И. Скрипка; Veronika Kogay; А. И. Листратов; А. А. Соколова; Д. А. Напалков; Victor Fomin

doi:10.26442/00403660.2019.07.000045

July 15, 2019Terapevticheskii arkhivOpen Access

Personalized approach for direct oral anticoagulant prescription: from theory to practice

View Full Paper

Ask AI

Bookmark

Share

Key result

Direct oral anticoagulant pharmacokinetics vary by renal function, age, drug interactions, and CES1/ABCB1/ABCG2/CYP3A5 polymorphisms, though clinical outcome data are currently limited to dabigatran.

Why the study?

Do clinical, pharmacokinetic, and pharmacogenetic factors influence the plasma concentrations, efficacy, and safety of direct oral anticoagulants in patients with atrial fibrillation?

Key Points

To review the influence of modifiable, non-modifiable, pharmacokinetic, and pharmacogenetic factors on the efficacy and safety of direct oral anticoagulants in patients with atrial fibrillation.
Narrative synthesis of clinical trials and pharmacological studies evaluating direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, and edoxaban).
Analysis of patient factors affecting drug exposure, including age, renal function, body weight, and genetic variations in metabolizing enzymes such as carboxylesterase 1 (CES1).
Patients aged 75 years and older exhibited a 68% increase in dabigatran trough concentration and a 2- to 3-fold higher risk of major bleeding.
Patients experiencing major bleeding had 36% higher mean peak (Cssmax) and 55% higher trough (Cssmin) dabigatran concentrations than those without bleeding complications.

Structured PICO

Do clinical, pharmacokinetic, and pharmacogenetic factors influence the plasma concentrations, efficacy, and safety of direct oral anticoagulants in patients with atrial fibrillation?

P

Population

Patients with atrial fibrillation receiving direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, edoxaban).

I

Intervention

Direct oral anticoagulants (dabigatran 150 or 110 mg twice daily, rivaroxaban 20 or 15 mg once daily, apixaban 5 or 2.5 mg twice daily, edoxaban 60 or 30 mg once daily) guided by clinical, pharmacokinetic, and pharmacogenetic factors (CES1, ABCB1, ABCG2, CYP3A4/5 polymorphisms)

Limitations

Data on the influence of genetic features on clinical response to DOACs are currently limited mainly to dabigatran (RE-LY subanalysis).
Genome-wide association studies in large cohorts have not been conducted for rivaroxaban, apixaban, or edoxaban.
Further large-scale long-term studies are needed to determine whether routine pharmacogenetic testing should be implemented for DOAC dose selection.
Evidence linking genetic polymorphisms to clinical outcomes on DOACs is currently limited to dabigatran (RE-LY-Genetics substudy).
Insufficient data exist to assess the clinical impact of pharmacogenetics on rivaroxaban, apixaban, and edoxaban outcomes.
Lack of large-scale prospective studies to justify routine genotyping for DOAC dose adjustment in clinical practice.

Ask about this paper

Answers are grounded in this paper and cite their sources.

Implication

This narrative review synthesizes how renal function, age, drug-drug interactions, and genetic polymorphisms (such as CES1, ABCB1, ABCG2, and CYP3A5) affect DOAC pharmacokinetics in atrial fibrillation, highlighting that while clinical factors guide current dosing, routine pharmacogenetic testing requires further validation in large trials.

Abstract

Data on possibilities of personalized approach for direct oral anticoagulants (DOAC) choice in patients with atrial fibrillation are presented in the article. We also review clinical and fundamental studies and future perspectives on pharmacogenetic and pharmacokinetic tests to predict the efficacy and safety of DOAC. В статье представлены данные о возможностях персонализированного подхода к назначению прямых оральных антикоагулянтов (ПОАК) у пациентов с фибрилляцией предсердий. Подробно обсуждается обзор клинических и научных исследований по возможностям и перспективам фармакогенетического и фармакокинетического тестирования для прогнозирования эффективного и безопасного применения ПОАК.

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

Скрипка et al. (2019) conducted a review in Atrial fibrillation. Direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, edoxaban) and pharmacogenetic/pharmacokinetic testing was evaluated. Direct oral anticoagulant pharmacokinetics vary by renal function, age, drug interactions, and CES1/ABCB1/ABCG2/CYP3A5 polymorphisms, though clinical outcome data are currently limited to dabigatran.

synapsesocial.com/papers/6a7b629d2eb3c7e469f44e5e https://doi.org/10.26442/00403660.2019.07.000045

View Full Paper

Ask AI

Bookmark

Share

Personalized approach for direct oral anticoagulant prescription: from theory to practice

Key Points

Structured PICO

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Personalized approach for direct oral anticoagulant prescription: from theory to practice

Key Points

Structured PICO

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Keep reading

Keep reading