Fast track — ArticlesDabigatran compared with warfarin in patients with atrial fibrillation and previous transient ischaemic attack or stroke: a subgroup analysis of the RE-LY trial
Introduction
Patients with atrial fibrillation are at a high risk of stroke, particularly if they have already had a transient ischaemic attack or an ischaemic stroke.1, 2 Oral anticoagulation with adjusted-dose warfarin is effective for the prevention of stroke in these patients.3 Dabigatran is an oral reversible direct thrombin inhibitor that can be given in fixed daily doses independent of age or bodyweight;4 it has a bioavailability of 6·5%, and about 80% of the dose is excreted by the kidney.5 By contrast with oral vitamin K antagonists, dabigatran does not require routine coagulation monitoring.5
Twice daily treatment with 110 mg or 150 mg dabigatran has been compared with adjusted-dose warfarin in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, a non-inferiority study in 18 113 patients who had atrial fibrillation and were at increased risk of stroke.6 The number of patients who had a stroke or systemic embolism was similar in the 110 mg dabigatran twice daily group but was lower in the 150 mg dabigatran twice daily group compared with the warfarin group. Compared with warfarin, 110 mg dabigatran twice daily was associated with lower rates of major haemorrhage and 150 mg dabigatran twice daily with similar rates. Intracranial haemorrhage was significantly reduced with both doses of dabigatran compared with warfarin.
In this prespecified subgroup analysis of RE-LY, we aimed to investigate whether the effects of dabigatran on secondary prevention of stroke in the subgroup of patients with previous transient ischaemic attack or ischaemic stroke—who are at high risk of recurrent stroke2 and are more susceptible to adverse events from anticoagulation, in particular cerebral haemorrhage3, 7—are consistent with the results in the entire study population.
Section snippets
Patients
The RE-LY trial, a PROBE (prospective randomised, open-label, blinded endpoint) study, was designed to establish the non-inferiority of two masked doses of dabigatran compared with adjusted warfarin in patients with atrial fibrillation who had an increased risk of stroke.8 18 113 patients from 967 centres in 44 countries were enrolled between December, 2005, and December, 2007. The trial had a median follow-up of 2·0 years (IQR 1·14–2·86).
Patients were eligible if they had atrial fibrillation
Results
In the RE-LY trial, 18 113 patients were enrolled, of whom 3623 (20·0%) had previously had a transient ischaemic attack or stroke (table 1): 2273 (12·5%) previously had a stroke, 1663 (9·2%) a transient ischaemic attack, and 313 (1·7%) both. One patient in the 110 mg dabigatran group did not provide information on history of stroke or transient ischaemic attack and so was excluded from the analyses. A CHADS2 score (a measure of the risk of stroke in which congestive heart failure, hypertension,
Discussion
In this subanalysis of the RE-LY study, we report a higher annual rate of stroke in patients with atrial fibrillation if they had already had a stroke or a transient ischaemic attack (panel). The stroke rates in the warfarin group of RE-LY (1·58% per year)6 were lower than reported in the European Atrial Fibrillation Trial (4% per year).3 In the Studio Italiano Fibrillazione Atrial study,10 which compared warfarin (INR 2·0–3·5) with indobufen in 916 patients with atrial fibrillation and recent
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2023, Neurologic ClinicsDirect oral anticoagulants compared with other strategies in patients with atrial fibrillation and stroke or transient ischemic attack: Systematic review
2023, Journal of the Formosan Medical AssociationComparison of primary and secondary stroke prevention in patients with nonvalvular atrial fibrillation: Results from the RAFFINE registry
2022, Journal of Stroke and Cerebrovascular DiseasesCitation Excerpt :Direct oral anticoagulant (DOAC) therapy does not require regular monitoring of coagulation and has equivalent efficacy for stroke prevention and a better safety profile, such as a lower rate of intracranial hemorrhage, compared with warfarin in patients with nonvalvular (NV) AF in randomized, controlled trials (RCTs).9-12 Subgroup analyses of these trials have shown that the effects of DOACs were consistent in patients with and without prior stroke or transient ischemic attack (TIA).13-16 DOACs have been available from 2010 in clinical practice in Japan and may have impacted anticoagulation therapy for stroke prevention in patients with NVAF.
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