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Updated: Sep 4, 2025
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Published on: October 12, 2012
Personalizing Direct Oral Anticoagulant Therapy for a Diverse Population: Role of Race, Kidney Function, Drug
Lorenzo E Thompson1, Brittney H Davis1, Renuka Narayan1
1Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Insights
Direct oral anticoagulants (DOACs) are widely used but show response variability. Research must include diverse populations to understand factors influencing DOAC effectiveness and safety, especially bleeding risks.
Area of Science:
- Pharmacology
- Genetics
- Cardiology
Background:
- Direct oral anticoagulants (DOACs) are preferred over warfarin for preventing thromboembolism and stroke in atrial fibrillation due to better safety and fewer interactions.
- Despite DOACs' advantages, bleeding complications remain a significant concern.
- Variability in DOAC response is common, influenced by patient-specific factors, medications, comorbidities, and genetics.
Purpose of the Study:
- To discuss factors affecting DOAC response, including clinical and genetic predictors.
- To highlight the need for research including diverse populations to understand DOAC variability.
- To address the under-representation of certain racial groups in current DOAC research.
Main Methods:
- Review of existing literature on factors influencing DOAC response.
- Discussion of clinical variables such as age, sex, weight, and kidney function.
- Exploration of pharmacogenetic associations and drug-drug interactions.
Main Results:
- DOAC response variability is multifactorial, involving clinical and genetic elements.
- Current evidence on DOAC pharmacogenetics is largely based on European and Asian populations.
- Lack of diversity in research limits generalizability of findings on DOAC response predictors.
Conclusions:
- DOAC-related bleeding risk necessitates a deeper understanding of response variability.
- Future research must prioritize inclusion of diverse ancestries to accurately assess clinical and genetic predictors of DOAC response.
- Engaging under-represented populations is crucial for equitable and effective DOAC therapy.
Abstract:
Oral anticoagulants (OACs) are commonly used to reduce the risk of venous thromboembolism and the risk of stroke in patients with atrial fibrillation. Endorsed by the American Heart Association, American College of Cardiology, and the European Society of Cardiology, direct oral anticoagulants (DOACs) have displaced warfarin as the OAC of choice for both conditions, due to improved safety profiles, fewer drug-drug and drug-diet interactions, and lack of monitoring requirements. Despite their widespread use and improved safety over warfarin, DOAC-related bleeding remains a major concern for patients. DOACs have stable pharmacokinetics and pharmacodynamics; however, variability in DOAC response is common and may be attributed to numerous factors, including patient-specific factors, concomitant medications, comorbid conditions, and genetics. Although DOAC randomized controlled trials included patients of varying ages and levels of kidney function, they failed to include patients of diverse ancestries. Additionally, current evidence to support DOAC pharmacogenetic associations have primarily been derived from European and Asian individuals. Given differences in genotype frequencies and disease burden among patients of different biogeographic groups, future research must engage diverse populations to assess and quantify the impact of predictors on DOAC response. Current under-representation of patients from diverse racial groups does not allow for proper generalization of the influence of clinical and genetic factors in relation to DOAC variability. Herein, we discuss factors affecting DOAC response, such as age, sex, weight, kidney function, drug interactions, and pharmacogenetics, while offering a new perspective on the need for further research including frequently excluded groups.
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