We searched MEDLINE and PubMed (date of last search May 2, 2016) using the following search terms: “atrial fibrillation”, “warfarin”, “dabigatran”, “rivaroxaban”, “apixaban”, “edoxaban”, “randomized trial”, “real world”, “cohort study”, “registry”, “stroke prevention”, “stroke risk”, and “bleeding risk”, and checked reference lists from relevant articles. No publication time limits were specified, though preference was given to articles from the past 10 years and some highly cited older
SeriesStroke prevention in atrial fibrillation
Introduction
Ischaemic strokes related to atrial fibrillation usually result from cardioembolism of a large cerebral artery, and therefore tend to be larger (figure 1) and more frequently fatal or associated with greater disability than strokes from other causes.1, 2, 3 However, strokes related to atrial fibrillation are largely preventable, because oral anticoagulants (OACs) are so effective. In meta-analyses,4, 5 vitamin K antagonists (VKAs; eg, warfarin) reduced stroke or systemic thromboembolism by 64% and all-cause mortality by 26% compared with placebo (five studies) or untreated controls (one study); the use of non-VKA OACs (NOACs) offers additional significant reductions of 19% and 10%, respectively, relative to warfarin.4, 5
Several steps are needed to reduce the stroke burden associated with atrial fibrillation. The first is recognition of the risk of stroke in patients with atrial fibrillation, followed by risk assessment using simple risk scores such as CHA2DS2-VASc, and prescription of appropriate stroke prevention to all who are not at low risk of stroke. Second, a system is needed to recognise the pre-symptomatic phase of atrial fibrillation rather than wait for stroke to be the first clinical manifestation. Finally, measures are needed to achieve optimum treatment, including excellent international normalised ratio (INR) control if VKAs are used, excellent adherence to thromboprophylactic drugs (ie, VKAs or NOACs) as prescribed, and long-term persistence with treatment. In this paper, we provide an overview of all three aspects of stroke prevention in atrial fibrillation, in the hope that greater awareness will result in reduction of the overall ischaemic stroke burden associated with atrial fibrillation.
Section snippets
Atrial fibrillation as a cause of ischaemic stroke
Of all strokes with an established cause, over 85% are ischaemic strokes,6 and the association of atrial fibrillation with ischaemic stroke of cardioembolic origin is well recognised.7 Indeed, findings from recent population-based studies or stroke registries8, 9, 10, 11, 12 consistently showed a substantial atrial-fibrillation-attributable risk of stroke, especially in the elderly; at least one in three to four patients with an ischaemic stroke, and over 80% of those with ischaemic stroke of
Previous management of atrial fibrillation in patients presenting with stroke
Although most strokes related to atrial fibrillation can be prevented using OACs,21 findings from contemporary registry-based and observational real-world reports from various geographical regions have consistently shown that OAC treatment is underused in patients with atrial fibrillation who are at risk of stroke.22 No OAC is used in around a third of eligible patients with atrial fibrillation, and in over 50% of patients who receive warfarin the quality of anticoagulation control remains
Finding unknown atrial fibrillation to prevent stroke
Almost 10% of all ischaemic strokes (representing >25% of strokes related to atrial fibrillation) occur simultaneously with first-detected atrial fibrillation. Measures to screen or case-find unknown asymptomatic atrial fibrillation, and then treat with OACs, should logically have a major effect on reducing stroke burden. The inbuilt assumptions are that unknown asymptomatic atrial fibrillation is common, and that prognosis of unknown asymptomatic atrial fibrillation is similar to that in the
Stroke risk factors and risk stratification
Atrial fibrillation increases the risk of stroke and systemic thromboembolism, but the excess risk also depends on the presence of various additional risk factors, which were defined from findings from the non-warfarin placebo or control arms of historical randomised trials done two decades ago52 or from large observational epidemiological studies. There is good evidence of increased risk in patients with previous stroke or systemic embolism, age at least 65 years, recent decompensated heart
Thromboprophylaxis in patients with atrial fibrillation
Guidelines recommend different approaches to thromboprophylaxis in atrial fibrillation. Some use CHA2DS2-VASc score in a categorical approach; for example, the American Heart Association/American College of Cardiology/Heart Rhythm Society guidelines68 define patients with atrial fibrillation as low, moderate, or high risk, and recommend antithrombotic treatment on that basis. Patients at high risk are those with a CHA2DS2-VASc score of at least 2, for whom OACs are recommended; low risk are
From clinical trials to real-world practice
The efficacy of warfarin compared with placebo or aspirin for stroke prevention in patients with non-valvular atrial fibrillation was established almost 30 years ago (table).4 In a meta-analysis86 of eight more recent stroke prevention trials (2005–11), the pooled rate of residual stroke or systemic embolism in the warfarin arms was significantly lower than in earlier trials (1·66% vs 2·09%), probably because of improved management of warfarin treatment (mean TTR 63·6% vs 42–81%, and four of
Specific management considerations
Because of the overlap in stroke and bleeding risk factors, high-risk patients with atrial fibrillation are often denied OACs without an absolute contraindication. Elderly people91 and most patients with a history of bleeding (eg, previous gastrointestinal bleeding with a healed culprit lesion) clearly benefit from OAC resumption.92 Patients with atrial fibrillation after intracerebral haemorrhage or those with severe renal disease represent other high-risk groups that were excluded from
Population-centred or patient-centred interventions
Nurse-led clinics are an attractive possibility to improve uptake of stroke prevention strategies. In a randomised trial of 712 patients,102 appropriate OAC prescription increased from a high base of 83% in the usual care group to 99% in the nurse-led clinic. Although cardiovascular death and hospital admissions were both significantly reduced by the intervention, stroke was infrequent, with only 1% of patients having stroke in 22 months of follow-up, and was not significantly different between
Future directions
Increasing awareness of the role of unrecognised atrial fibrillation should accelerate efforts to detect atrial fibrillation before stroke has occurred and institute effective thromboprophylaxis with OACs. Widespread recognition of the role of undertreatment of atrial fibrillation in causation of ischaemic stroke will be of crucial importance to focus efforts to close the evidence–treatment gap for OACs, and replace aspirin with OACs in the therapeutic armamentarium. Basic and clinical research
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