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CNS Drugs

, Volume 22, Issue 10, pp 815–825 | Cite as

Effect of Race/Ethnicity on the Efficacy of Warfarin

Potential Implications for Prevention of Stroke in Patients with Atrial Fibrillation
  • Albert Yuh-Jer ShenEmail author
  • Wansu Chen
  • Janis F. Yao
  • Somjot S. Brar
  • Xunzhang Wang
  • Alan S. Go
Current Opinion

Abstract

Atrial fibrillation (AF) is the most common sustained arrhythmia seen in clinical practice. It affects approximately 6% of persons over 65 years of age and is independently associated with a 4-to 5-fold higher risk of ischaemic stroke and a 2-fold higher risk of death. Randomized controlled trials have shown that treatment with adjusted-dose oral vitamin K antagonists (primarily warfarin with a target international normalized ratio [INR] of 2.0–3.0) reduces the relative risk of ischaemic stroke by two-thirds (an approximately 3% reduction in annual absolute risk), but is associated with a 0.2% excess annual absolute risk of intracranial haemorrhage (ICH). However, in ‘real world’ studies, the risk reductions in ischaemic stroke with warfarin have been significantly lower (25–50% relative risk reduction) than in selected trial samples. Moreover, more than 90% of patients enrolled in the sentinel trials were White/European. This raises the question of whether the beneficial results of warfarin can be extrapolated to persons of colour. Important differences in stroke risk profile and responsiveness to warfarin exist across racial/ethnic groups, such that one cannot assume a priori that there is a net benefit of warfarin therapy for AF patients of all racial/ethnic groups.

Among patients with ischaemic stroke, AF is more likely to be implicated as the cause of stroke in the White population than in other racial/ethnic groups. Furthermore, AF may be a stronger predictor of ischaemic stroke among the White population than in Black or Hispanic/Latino populations. Approximately one-third of strokes in AF patients are noncardioembolic. Warfarin has been shown to be ineffective in preventing recurrent noncardioembolic strokes. Many persons of colour with AF have other risk factors that predispose them to noncardioembolic stroke, which may partially explain why warfarin has been reported to be less efficacious in preventing strokes in non-White patients with AF, even after adjustment for co-morbidities and anticoagulation monitoring. Notably, the background incidence of ICH is higher in Black, Hispanic and Asian patients than in White patients. Any greater than expected increases in bleeding secondary to anticoagulation may potentially offset any benefit gained from cardioembolic stroke reduction, although this has not been fully resolved.

Finally, there are racial/ethnic differences in the prevalence of certain polymorphisms in genes that influence warfarin pharmacokinetics and pharmaco-dynamics (e.g. cytochrome P450 2C9 and vitamin K epoxide reductase). The Asian population generally appear to require the lowest daily dose of warfarin to maintain a given INR target, with the White population requiring an intermediate daily dose and the Black population requiring the highest daily dose. These differences must be taken into account when administering warfarin in order to minimize the risk of under-or over-anticoagulation.

In summary, warfarin is highly effective in preventing ischaemic strokes in White patients with AF at a modestly higher risk of ICH. Whether the same net clinical benefit extends to persons of colour is unproven. Given the rapidly changing demographic nationally and internationally, additional research is needed to resolve this important question.

Keywords

Atrial Fibrillation Warfarin Ischaemic Stroke Black Patient White Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

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Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  • Albert Yuh-Jer Shen
    • 1
    Email author
  • Wansu Chen
    • 2
  • Janis F. Yao
    • 2
  • Somjot S. Brar
    • 3
  • Xunzhang Wang
    • 4
  • Alan S. Go
    • 5
  1. 1.Department of CardiologyKaiser Permanente Medical CenterLos AngelesUSA
  2. 2.Department of Research and EvaluationKaiser Permanente of Southern CaliforniaPasadenaUSA
  3. 3.Center for Interventional Vascular TherapyColumbia University Medical CenterNew YorkUSA
  4. 4.Department of ElectrophysiologyKaiser Permanente Medical CenterLos AngelesUSA
  5. 5.Division of ResearchKaiser Permanente of Northern CaliforniaOaklandUSA

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