Reports of randomised trials of antithrombotic therapy in patients with AF were selected by searching PubMed, EMBASE, and the Cochrane Database, from 1975 to August, 2007, with the terms “atrial fibrillation”, “stroke”, “thromboembolism”, “stroke prevention”, “warfarin”, “oral anticoagulation”, “aspirin”, “antiplatelet therapy”, “antithrombotic therapy”, and “thromboprophylaxis”. References from reviews and meta-analyses were manually sought. Short-term studies (<3 months) and studies of
ReviewAtrial fibrillation and stroke prevention
Introduction
Atrial fibrillation (AF) is a common arrhythmia, which is seen in everyday clinical practice. The prevalence of AF increases from less than 1% in patients younger than 60 years to almost 10% in patients over the age of 80 years.1 Similarly, the incidence of AF increases from 0·2% per year in men under the age of 40 years to more than 2% per year in men aged 80–89 years, with a lower age-adjusted incidence in women.2, 3 Therefore, AF is predominantly a problem of the older population, and the prevalence of AF is projected to rise as the population ages and the prevalence of cardiovascular risk factors increases.4 Indeed, the rising prevalence and incidence of AF have already been reported in several studies of secular trends during the past two decades.5, 6 The authors of the Olmstead County study4 reported that the age-adjusted and sex-adjusted incidence of AF per 1000 person-years was 3·04 (95% CI 2·78–3·31) in 1980 and 3·68 (3·42–3·95) in 2000, with a relative increase of 12·6% (2·1%–23·1%) in total. This analysis estimates that the number of people with AF in the USA will be 12·1 million by 2050, assuming no further increase in age-adjusted incidence of AF, and 15·9 million if the increase in incidence continues.
AF accounts for more than 1% of health-care expenditure in the UK,7 and treatment of thromboembolic stroke incurs a significant share of the health-care costs associated with AF.8 On a population level, AF is associated with a fourfold to fivefold increase in the risk of stroke, and an estimated 15% of all strokes are caused by AF; importantly, this proportion increases substantially with age.9 In a selected population of patients with ischaemic stroke, AF was highly prevalent (almost 25%) and associated with longer stays in hospital, greater disability, higher rates of stroke recurrence, and higher rates of mortality compared with stroke patients without AF.10 The risk of stroke in patients with paroxysmal or persistent AF is comparable to the risk in patients with permanent AF11 and, importantly, the absence of symptoms (eg, palpitations) does not imply lower risk of thromboembolism.12
The aim of this Review is to give an overview of antithrombotic therapy for stroke prevention in AF. We discuss risk factors for stroke, risk stratification, and new developments for stroke prevention in patients with AF.
Section snippets
Pathophysiology of ischaemic stroke in AF
More than 150 years ago, Rudolf Virchow proposed a triad of abnormalities—vessel wall abnormalities, abnormal stasis, and abnormal blood constituents—required for thrombus formation (thrombogenesis). The criteria for Virchow's triad are fulfilled in AF: structural heart disease (vessel wall abnormalities and endothelial or endocardial damage or dysfunction), blood stasis within the left atrium and its appendage, and abnormalities of coagulation or platelets and fibrinolysis (abnormal blood
Warfarin versus placebo
Six randomised, controlled clinical trials have compared warfarin with either control or placebo for the prevention of stroke in patients with non-valvular AF (table 1).17, 18, 19, 20, 21, 22, 23 With the exception of the EAFT22 (European Atrial Fibrillation Trial), all these trials were primary prevention studies. The EAFT was the only trial that involved only a secondary prevention study population, and compared anticoagulation, aspirin, and placebo in patients with non-valvular AF who had
Antithrombotic therapy and stroke subtypes
Criteria that enable the discrimination between embolic and non-embolic stroke have been defined.53 Although accurate subtyping of stroke might not be possible in all cases, even with advanced neuroimaging and vascular imaging techniques, and some lacunar strokes might have cardioembolic or atheroembolic origins, the classification of stroke subtypes might have clinical significance. Notably, stroke recurrence tends to be the same subtype as the first event,54 and the short-term risk of death
Antithrombotic therapy and cognitive function
In addition to increased risk of stroke and thromboembolism, AF is associated with poor cognitive function. Data from cross-sectional studies show an association among non-valvular AF, silent cerebral infarction, and decreased cognitive function, which is sometimes misdiagnosed as mild Alzheimer's disease. For example, one large study64 reported that impaired cognitive function was worse in patients with AF and focal neurological deficits compared with patients with AF alone, patients with
Stroke risk assessment in patients with AF
The use of antithrombotic therapy must be balanced with the anticipated benefit of reduced thromboembolic complications and the potential risk of bleeding in patients with AF. The absolute benefit of anticoagulation therapy is directly related to the absolute risk of thromboembolic complications. The absolute benefits of anticoagulation and antiplatelet therapy are smaller in the context of primary prevention, where the absolute risk of stroke is low (Table 1, Table 2). Therefore, the use of
Barriers to anticoagulation therapy
Despite the well recognised association between AF and ischaemic stroke, and the benefits of anticoagulation therapy, a large proportion of patients with AF are not treated with warfarin.96 The perceptions of physicians and patients can influence the use of anticoagulation therapy. Patients in clinical trials will inevitably be a selected population, and physicians might challenge the validity of randomised clinical trials and, in particular, the risk of bleeding versus the benefit of warfarin
Conclusions
AF is associated with an increased risk of thromboembolic complications, a risk that can be reduced with antithrombotic therapy. Careful assessment of the absolute risk of stroke and bleeding complications will guide the use of appropriate thromboprophylaxis. Anticoagulation therapy, however, is underused despite well documented efficacy in clinical trials. This might be because of concerns in clinical practice about effectiveness and bleeding risk, and patient perceptions of and compliance
Search strategy and selection criteria
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