Temporal trends of stroke severity and the association between antithrombotic drug regimen changes and clinical outcomes after stroke in atrial fibrillation

Abstract Background Stroke prevention is central to the management of patients with atrial fibrillation (AF) but the impact of NOACs on stroke severity from a nationwide perspective, and the impact of changes in antithrombotic regimen following an ischaemic stroke on subsequent clinical events is unceratin. The aims of the present study were as follows: (i) to describe the temporal trends in OAC use between 2012-2018, and the relationship to stroke severity at presentation; (ii) to describe antithrombotic therapy prescribing patterns following an ischaemic stroke, and the impact of post-stroke thromboprophylaxis on outcomes; and (iii) to assess the impact of changing OAC strategy in AF patients on a NOAC presenting with an ischaemic stroke. Methods From 2007 to 2018, a total of 63,365 patients were identified from the “National Health Insurance Research Database (NHIRD)” in Taiwan. The stroke prevention strategy before and after ischemic stroke and its association to stroke severity was analysed. Subsequent clinical events after ischaemic stroke included recurrent ischaemic stroke, intracranial haemorrhage (ICH), major bleeding, all-cause mortality and composite outcomes. Results The temporal trend disclosed that the overall OAC prescription rate was rising, with warfarin used declining and NOACs use increasing, which was associated with a gradual decline of moderate-severe and severe strokes. The post-stroke antithrombotic strategy was variable. Compared to NOACs post-stroke, there was a significant increase in ischaemic stroke and mortality in non-anticoagulated (adjusted hazard ratios [aHRs] 1.804 and 3.441, respectively) and antiplatelet users (aHRs 1.785 and 1.483, respectively). Warfarin use post-stroke was associated with a significantly incresaed risk of major bleeding compared to NOACs (aHR 2.839). Non-anticoagulated and antiplatelet users were associated with higher risks of both composite outcomes compared to NOAC. Among 769 patients who received NOACs before stroke and continued NOAC post-stroke, there was a higher risk of ischaemic stroke and composite outcomes with no difference in major bleeding, mortality or ICH if patients were changed to a different NOAC post-stroke. Conclusions In this nationwide cohort study, increasing use of NOACs was associated with a decline of moderate-severe and severe strokes. Compared to NOACs, non-anticoagulation and antiplatelet use were associated with a significant increase in ischaemic stroke, mortality, and the composite outcome with no significant differences in bleeding events. There was no significant difference of ischemic stroke, mortaltiy, and ICH between post-stroke warfarin and NOAC use but warfarin was associated with a significantly increased risk of major bleeding. A change of NOAC types after ischemic stroke was associated with a two-fold higher risk of ischaemic stroke and the composite outcomes.