Contemporary ReviewStroke prevention in atrial fibrillation—An Asian stroke perspective
Introduction
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with increased morbidity and mortality worldwide.1, 2 Having AF increases the likelihood of thromboembolic events, heart failure, and hospitalization and reduces quality of life, exercise capacity, and left ventricular function.2 Ischemic stroke secondary to AF is more severe than that due to other causes and is independent of advanced age and other stroke risk factors.2 Indeed, AF independently predicts poor clinical outcomes in patients with ischemic stroke.3 Stroke prevention in AF is therefore crucially important.
Patients with nonvalvular AF (NVAF) are at a 5-fold higher risk of ischemic stroke than those without AF, with up to 20% of all strokes possibly attributable to AF.2 The Framingham Heart Study showed that the risk of AF-related stroke increases with age, from 1.5% in 50–59-year-olds to 23.5% in octogenarians.1 Similarly, stroke prevalence increases with age in Asia; for example, in China it rises from 4.3% in patients younger than 40 years to 32.9% in patients older than 80 years.4 Importantly, the burden of AF-related stroke is expected to increase as aging populations grow.
Compared to Europe and the United States, few stroke prevention studies have been conducted in Asian patients with AF. Current international guidelines are based almost exclusively on data from numerous studies in predominantly Caucasian populations. In addition, there is a wide variation in the therapeutic approaches for AF treatment. In this context, detailed analysis of relevant Asian AF and anticoagulation data can shed light on regional differences and how these may influence patient outcomes. This review summarizes the available clinical data from Asian countries, with the intention of formulating an appropriate and actionable stroke prevention strategy for AF in Asia.
We searched MEDLINE by using the following terms individually and/or in combination: “atrial fibrillation,” “rate control,” “rhythm control,” “antithrombotic therapy,” “anticoagulation,” “stroke risk,” “bleeding risk,” “antiplatelet therapy,” “Asia,” “ethnic difference” between January 1, 1990, to January 1, 2013. In addition, publications from regional journals and abstracts from national and international cardiovascular meetings were studied to identify studies related to AF in Asia.
Section snippets
Epidemiology
The prevalence of AF in predominantly Caucasian populations is 1%–2%, whereas studies in Asia consistently report lower prevalence (~1%) (Figure 1). Nevertheless, the majority of data from Asia were limited by the observational cohort study design of a single electrocardiographic recording. Therefore, these data need be interpreted with caution. However, recent research in the United States did corroborate the ethnic difference, with AF prevalence in Asians half that observed in Caucasians.5
Risk factors and comorbidities for AF
Most Asian data on the risk factors for AF derive from cross-sectional community cohort rather than prospective studies. Similar to Caucasians,9, 10, 11 major risk factors for AF in Asians include age, male gender, and structural heart diseases, especially heart failure and valvular heart disease (Online Supplement Table 1). Chronic rheumatic heart disease is a major cause of AF in developing countries, especially in younger age groups; for example, it caused AF in almost 25% of the patients in
Risk stratification for stroke
Compared to the 5-fold higher likelihood of stroke among Caucasian patients with AF,2 stroke risk related to AF in Asians is typically lower: relative risks are 2.78 in China,6 3.60 in Singapore,15 3.70 in Japanese men,16 and 3.87 in Taiwan.17 However, the relative risk of stroke-related AF in patients with chronic rheumatic heart disease remains unclear. Nevertheless, the relative risk of AF-related mortality in Asian patients—1.88 in Japan18 and 2.23 in Taiwan17—is similar to Caucasians.19
Optimal antithrombotic therapies for thromboprophylaxis in AF
Asian patients suffering from AF-associated ischemic stroke have a similar risk of mortality as Caucasians.16, 17 Data on the oral anticoagulant (OAC) therapies for thromboprophylaxis in Asian patients with AF are scarce. Current clinical guidelines in Asia (Online Supplement Table 3), including the risk stratification and international normalized ratio (INR) target range, are based on data derived from predominantly Caucasian populations. A major barrier to greater use of anticoagulation in
New pharmacological and nonpharmacological therapies
Although warfarin is a highly effective thromboprophylactic in AF, it has many limitations; for example, the need for close monitoring, possible food/drug interactions, and genetic polymorphism complicate its use in Asian patients. The recent development of new OACs that can potentially circumvent some of these shortcomings may provide a safe, effective, and convenient alternative to warfarin. Two new OAC classes—factor Xa inhibitors (rivaroxaban and apixaban) and a direct thrombin inhibitor
Factor Xa inhibitors
Rivaroxaban was well tolerated in elderly Chinese patients, with predictable metabolism and activity, and no need for dose adjustment in different ethnicities or genders.38 In the ROCKET AF trial39 (included ~15% of the patients recruited from Asia-Pacific regions), rivaroxaban 20 mg once daily proved noninferior to warfarin in preventing stroke and systemic embolism. There was no significance between-treatment difference in the rates of major bleeding; however, intracranial and fatal bleeds
Direct thrombin inhibitors
Dabigatran is the only direct thrombin inhibitor approved for preventing stroke in NVAF. In the RE-LY trial, dabigatran 110 mg twice daily was associated with similar stroke and systemic embolism rates to warfarin, but had a lower rate of major hemorrhage. Although dabigatran 150 mg twice daily was superior to warfarin in reducing stroke and systemic embolism, it incurred a similar rate of major hemorrhage.46 The findings of a subgroup analysis of Japanese patients in the RE-LY trial (n = 326)47
Conclusions
Although this review identifies some of the potential differences in the epidemiology and treatment of AF in Asia compared with the West, it is not a meta-analysis because of the paucity of studies examining AF risk in Asia and those observations are mainly based on limited retrospective or cross-sectional community cohort studies. Moreover, Asian populations are much more heterogeneous than Western populations and it is difficult to generalize any findings from one country to other countries.
Acknowledgments
Dr David Neil of UBM Medica Asia Pte Ltd provided writing and editorial support, which was funded by Boehringer Ingelheim.
References (51)
- et al.
Epidemiology, risk factors for stroke, and management of atrial fibrillation in China
J Am Coll Cardiol
(2008) - et al.
Development of a risk score for atrial fibrillation (Framingham Heart Study): a community-based cohort study
Lancet
(2009) - et al.
Annual incidence of atrial fibrillation and related factors in adults
Am J Cardiol
(2010) - et al.
Atrial fibrillation and obesity among older Chinese: the Guangzhou Biobank Cohort Study
Int J Cardiol
(2011) - et al.
Low prevalence of atrial fibrillation in community-dwelling Chinese aged 55 years or older in Singapore: a population-based study
J Electrocardiol
(2008) - et al.
Atrial fibrillation prevalence, incidence and risk of stroke and all-cause death among Chinese
Int J Cardiol
(2010) - et al.
Acute ischemic stroke in the very elderly Chinese: risk factors, hospital management and one-year outcome
Clin Neurol Neurosurg
(2011) Stroke in atrial fibrillation: epidemiology and thromboprophylaxis
J Thrombosis Haemost
(2011)- et al.
Racial/ethnic differences in the risk of intracranial hemorrhage among patients with atrial fibrillation
J Am Coll Cardiol
(2007) - et al.
Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial
Lancet
(2010)
Compliance with antithrombotic prescribing guidelines for patients with atrial fibrillation—a nationwide descriptive study in Taiwan
Clin Ther
Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial
Lancet
Population pharmacokinetic analysis of the oral thrombin inhibitor dabigatran etexilate in patients with non-valvular atrial fibrillation from the RE-LY trial
J Thromb Haemost
Atrial fibrillation as an independent risk factor for stroke: the Framingham Study
Stroke
2012 focused update of the ESC guidelines for the management of atrial fibrillation: an update of the 2010 ESC guidelines for the management of atrial fibrillation
Eur Heart J
Factors associated with in-hospital mortality after administration of thrombolysis in acute ischemic stroke patients: an analysis of the nationwide inpatient sample 1999 to 2002
Stroke
Racial/ethnic differences in the prevalence of atrial fibrillation among older adults—a cross-sectional study
J Natl Med Assoc
An epidemiological study on the prevalence of atrial fibrillation in the Chinese population of mainland China
J Epidemiol
Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention. The AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study
JAMA
Chronic kidney disease is associated with the incidence of atrial fibrillation: the Atherosclerosis Risk in Communities (ARIC) study
Circulation
Management of atrial fibrillation in rheumatic valvular heart disease
Curr Opin Cardiol
Incidence and risk factors for subtypes of cerebral infarction in a general population: the Hisayama study
Stroke
Mortality risk attributable to atrial fibrillation in middle-aged and elderly people in the Japanese general population: nineteen-year follow-up in NIPPON
Circ J
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This review is based on the Proceedings of an Asia Medical Stroke Prevention in Atrial Fibrillation Advisory Board, which was held with the support of Boehringer Ingelheim (Singapore).
Dr Clemens and Dr Lim were employees of Boehringer Ingelheim. The other authors are members of an Asia Medical Stroke Prevention in Atrial Fibrillation Advisory Board and received honoraria from Boehringer Ingelheim (Singapore) for their service in this capacity.