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 pharmacodynamics (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.