Timing of oral anticoagulation in atrial fibrillation patients after acute ischaemic stroke and outcome after 3 months: results of the multicentre Berlin Atrial Fibrillation Registry.

BACKGROUND: Oral anticoagulation (OAC) is key in stroke prevention in patients with atrial fibrillation (AF) but there is uncertainty regarding the optimal timing of OAC (re)initiation after stroke, as recent large randomised controlled trials have methodological weaknesses and excluded stroke patients on therapeutic anticoagulation at stroke onset as well as patients started on a vitamin K antagonist after stroke. The '1-3-6-12 days rule', based on expert consensus and referring to stroke severity, was used in clinical practice to initiate OAC after acute ischaemic stroke or transient ischaemic attack (TIA) since publication in 2013. METHODS: We retrospectively assessed whether compliance to the '1-3-6-12 days rule' was associated with the composite endpoint (recurrent stroke, systemic embolism, myocardial infarction, major bleeding or all-cause death). RESULTS: Among 708 registry patients with known AF before stroke and hospitalisation within 72 hours after stroke, 432 were anticoagulated at stroke onset. OAC was started according to the '1-3-6-12 days rule' in 255 (39.2%) patients. Non-adherence to the '1-3-6-12 days rule' was not associated with the composite endpoint within 3 months in 661 patients who (re-)started on OAC (log-rank test: p=0.74).Results were similar for 521 patients (re)started on a non-vitamin K-dependent OAC. CONCLUSION: (Re)starting OAC after stroke followed the '1-3-6-12 days rule' in about 40% of all patients with AF, and more often in those anticoagulated at stroke onset. Adherence to the '1-3-6-12 days rule' did not reduce the composite clinical endpoint, if OAC was restarted within 3 months of stroke/TIA. TRIAL REGISTRATION NUMBER: NCT02306824.

Off-label-dosing of non-vitamin K-dependent oral antagonists in AF patients before and after stroke: results of the prospective multicenter Berlin Atrial Fibrillation Registry.

AIMS: We aimed to analyze prevalence and predictors of NOAC off-label under-dosing in AF patients before and after the index stroke. METHODS: The post hoc analysis included 1080 patients of the investigator-initiated, multicenter prospective Berlin Atrial Fibrillation Registry, designed to analyze medical stroke prevention in AF patients after acute ischemic stroke. RESULTS: At stroke onset, an off-label daily dose was prescribed in 61 (25.5%) of 239 NOAC patients with known AF and CHA2DS2-VASc score ≥ 1, of which 52 (21.8%) patients were under-dosed. Under-dosing was associated with age ≥ 80 years in patients on rivaroxaban [OR 2.90, 95% CI 1.05-7.9, P = 0.04; n = 29] or apixaban [OR 3.24, 95% CI 1.04-10.1, P = 0.04; n = 22]. At hospital discharge after the index stroke, NOAC off-label dose on admission was continued in 30 (49.2%) of 61 patients. Overall, 79 (13.7%) of 708 patients prescribed a NOAC at hospital discharge received an off-label dose, of whom 75 (10.6%) patients were under-dosed. Rivaroxaban under-dosing at discharge was associated with age ≥ 80 years [OR 3.49, 95% CI 1.24-9.84, P = 0.02; n = 19]; apixaban under-dosing with body weight ≤ 60 kg [OR 0.06, 95% CI 0.01-0.47, P < 0.01; n = 56], CHA2DS2-VASc score [OR per point 1.47, 95% CI 1.08-2.00, P = 0.01], and HAS-BLED score [OR per point 1.91, 95% CI 1.28-2.84, P < 0.01]. CONCLUSION: At stroke onset, off-label dosing was present in one out of four, and under-dosing in one out of five NOAC patients. Under-dosing of rivaroxaban or apixaban was related to old age. In-hospital treatment after stroke reduced off-label NOAC dosing, but one out of ten NOAC patients was under-dosed at discharge. CLINICAL TRIAL REGISTRATION: NCT02306824.