Elsevier

The Lancet

Volume 388, Issue 10046, 20–26 August 2016, Pages 806-817
The Lancet

Series
Stroke prevention in atrial fibrillation

https://doi.org/10.1016/S0140-6736(16)31257-0Get rights and content

Summary

Atrial fibrillation is found in a third of all ischaemic strokes, even more after post-stroke atrial fibrillation monitoring. Data from stroke registries show that both unknown and untreated or under treated atrial fibrillation is responsible for most of these strokes, which are often fatal or debilitating. Most could be prevented if efforts were directed towards detection of atrial fibrillation before stroke occurs, through screening or case finding, and treatment of all patients with atrial fibrillation at increased risk of stroke with well-controlled vitamin K antagonists or non-vitamin K antagonist anticoagulants. The default strategy should be to offer anticoagulant thromboprophylaxis to all patients with atrial fibrillation unless defined as truly low risk by simple validated risk scores, such as CHA2DS2-VASc. Assessment of bleeding risk using the HAS-BLED score should focus attention on reversible bleeding risk factors. Finally, patients need support from physicians and various other sources to start anticoagulant treatment and to ensure adherence to and persistence with treatment in the long term.

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

Search strategy and selection criteria

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

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