BackgroundAtrial fibrillation (AF) known before ischemic stroke (KAF) has been postulated to be an independent category with a recurrence risk higher than that of AF detected after stroke (AFDAS). However, it is unknown whether this risk difference is confounded by pre‐existing anticoagulation, which is most common in KAF and also indicates a high ischemic stroke recurrence risk.MethodsIndividual patient data analysis from 5 prospective cohorts of anticoagulated patients following AF‐associated ischemic stroke. We compared the primary (ischemic stroke recurrence) and secondary outcome (all‐cause death) among patients with AFDAS versus KAF and among anticoagulation‐naïve versus previously anticoagulated patients using multivariable Cox, Fine‐Gray models, and goodness‐of‐fit statistics to investigate the relative independent prognostic importance of AF‐category and pre‐existing anticoagulation.ResultsOf 4,357 patients, 1,889 (43%) had AFDAS and 2,468 (57%) had KAF, while 3,105 (71%) were anticoagulation‐naïve before stroke and 1,252 (29%) were previously anticoagulated. During 6,071 patient‐years of follow‐up, we observed 244 recurrent strokes and 661 deaths. Only pre‐existing anticoagulation (but not KAF) was independently associated with a higher hazard for stroke recurrence in both Cox and Fine‐Gray models. Models incorporating pre‐existing anticoagulation showed better fit than those with AF category; adding AF‐category did not result in better model fit. Neither pre‐existing anticoagulation nor KAF were independently associated with death.ConclusionOur findings challenge the notion that KAF and AFDAS are clinically relevant and distinct prognostic entities. Instead of attributing an independently high stroke recurrence risk to KAF, future research should focus on the causes of stroke despite anticoagulation to develop improved preventive treatments. ANN NEUROL 2023;94:43–54

Background: Data on the safety and effectiveness of once-daily (QD) versus twice-daily (BID) direct oral anticoagulants (DOAC) in comparison to vitamin K antagonists (VKA) and to one another in patients with atrial fibrillation (AF) and recent stroke are scarce. Patients and methods: Based on prospectively obtained data from the observational registry Novel-Oral-Anticoagulants-in-Ischemic-Stroke-Patients(NOACISP)-LONGTERM (NCT03826927) from Basel, Switzerland, we compared the occurrence of the primary outcome – the composite of recurrent ischemic stroke, major bleeding, and all-cause death – among consecutive AF patients treated with either VKA, QD DOAC, or BID DOAC following a recent stroke using Cox proportional hazards regression including adjustment for potential confounders. Results: We analyzed 956 patients (median age 80 years, 46% female), of whom 128 received VKA (13.4%), 264 QD DOAC (27.6%), and 564 BID DOAC (59%). Over a total follow-up of 1596 patient-years, both QD DOAC and BID DOAC showed a lower hazard for the composite outcome compared to VKA (adjusted HR [95% CI] 0.69 [0.48, 1.01] and 0.66 [0.47, 0.91], respectively). Upon direct comparison, the hazard for the composite outcome did not differ between patients treated with QD versus BID DOAC (adjusted HR [95% CI] 0.94 [0.70, 1.26]). Secondary analyses focusing on the individual components of the composite outcome revealed no clear differences in the risk-benefit profile of QD versus BID DOAC. Discussion and conclusion: The overall benefit of DOAC over VKA seems to apply to both QD and BID DOAC in AF patients with a recent stroke, without clear evidence that one DOAC dosing regimen is more advantageous than the other.