ObjectiveTo investigate the aetiology, subsequent preventive strategies and outcomes of stroke despite anticoagulation in patients with atrial fibrillation (AF).MethodsWe analysed consecutive patients with AF with an index imaging-proven ischaemic stroke despite vitamin K-antagonist (VKA) or direct oral anticoagulant (DOAC) treatment across 11 stroke centres. We classified stroke aetiology as: (i) competing stroke mechanism other than AF-related cardioembolism; (ii) insufficient anticoagulation (non-adherence or low anticoagulant activity measured with drug-specific assays); or, (iii) AF-related cardioembolism despite sufficient anticoagulation. We investigated subsequent preventive strategies with regard to the primary (composite of recurrent ischaemic stroke, intracranial haemorrhage, death) and secondary endpoint (recurrent ischaemic stroke) within 3 months after index stroke.ResultsAmong 2946 patients (median age 81 years; 48% women; 43% VKA, 57% DOAC), stroke aetiology was competing mechanism in 713 patients (24%), insufficient anticoagulation in 934 (32%) and cardioembolism despite sufficient anticoagulation in 1299 (44%). We found high rates of the primary (27% of patients; completeness 91.6%) and secondary endpoint (4.6%; completeness 88.5%). Only DOAC (vs VKA) treatment after index stroke showed lower odds for both endpoints (primary: adjusted OR (aOR) (95% CI) 0.49 (0.32 to 0.73); secondary: 0.44 (0.24 to 0.80)), but not switching between different DOAC types. Adding antiplatelets showed higher odds for both endpoints (primary: aOR (95% CI) 1.99 (1.25 to 3.15); secondary: 2.66 (1.40 to 5.04)). Only few patients (1%) received left atrial appendage occlusion as additional preventive strategy.ConclusionsStroke despite anticoagulation comprises heterogeneous aetiologies and cardioembolism despite sufficient anticoagulation is most common. While DOAC were associated with better outcomes than VKA, adding antiplatelets was linked to worse outcomes in these high-risk patients. Our findings indicate that individualised and novel preventive strategies beyond the currently available anticoagulants are needed.Trial registration numberISRCTN48292829.

Background and Purpose— Heart failure (HF) in patients with acute ischemic stroke constitutes the source of various detrimental pathophysiologic mechanisms including prothrombotic and proinflammatory states, worsening of cerebral tissue oxygenation, and hemodynamic impairment. In addition, HF might affect the safety and efficacy of the acute recanalization stroke therapies. Methods— Patients treated with intravenous recombinant tissue-type plasminogen activator or mechanical recanalization at a universitary stroke center were included into a prospective registry. Patients received cardiological evaluation, including echocardiography, during acute care. Functional outcome was assessed after 90 days by structured telephone interviews. Safety and efficacy of intravenous thrombolysis and mechanical thrombectomy were investigated among patients with HF and compared with patients with normal cardiac function after propensity score matching. Results— One thousand two hundred nine patients were included. HF was present in 378 patients (31%) and an independent predictor of unfavorable functional outcome. Recanalization rates were equal among patients with HF after intravenous thrombolysis and after mechanical recanalization or combined treatment. The rate of secondary intracranial hemorrhage was not different (7% versus 8%; P =0.909 after thrombolysis and 15% versus 20%, P =0.364 after mechanical recanalization or combined therapy). Early mortality within 48 hours after admission was equal (<1.5% in both groups). Conclusions— In this real-world cohort of patients with stroke, HF was an independent predictor of unfavorable functional long-term outcome, while the safety and efficacy of intravenous thrombolysis and mechanical recanalization appeared unaffected.

Objective To investigate the safety and effectiveness of direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) after recent stroke in patients with atrial fibrillation (AF) aged ≥85 years. Methods Individual patient data analysis from seven prospective stroke cohorts. We compared DOAC versus VKA treatment among patients with AF and recent stroke (<3 months) aged ≥85 versus <85 years. Primary outcome was the composite of recurrent stroke, intracranial hemorrhage (ICH) and all‐cause death. We used simple, adjusted, and weighted Cox regression to account for confounders. We calculated the net benefit of DOAC versus VKA by balancing stroke reduction against the weighted ICH risk. Results In total, 5,984 of 6,267 (95.5%) patients were eligible for analysis. Of those, 1,380 (23%) were aged ≥85 years and 3,688 (62%) received a DOAC. During 6,874 patient‐years follow‐up, the impact of anticoagulant type (DOAC versus VKA) on the hazard for the composite outcome did not differ between patients aged ≥85 (HR≥85y = 0.65, 95%‐CI [0.52, 0.81]) and < 85 years (HR<85y = 0.79, 95%‐CI [0.66, 0.95]) in simple (pinteraction = 0.129), adjusted (pinteraction = 0.094) or weighted (pinteraction = 0.512) models. Analyses on recurrent stroke, ICH and death separately were consistent with the primary analysis, as were sensitivity analyses using age dichotomized at 90 years and as a continuous variable. DOAC had a similar net clinical benefit in patients aged ≥85 (+1.73 to +2.66) and < 85 years (+1.90 to +3.36 events/100 patient‐years for ICH‐weights 1.5 to 3.1). Interpretation The favorable profile of DOAC over VKA in patients with AF and recent stroke was maintained in the oldest old. ANN NEUROL 2022;91:78–88

Background and purpose Atrial fibrillation (AF) in stroke patients can be classified as either “known AF” (KAF), defined as AF confirmed before stroke onset, or “AF detected after stroke” (AFDAS), defined as AF diagnosed after stroke onset. While KAF is considered primarily cardiogenic, AFDAS includes patients with stroke‐triggered neurogenic arrhythmias. This study aimed to investigate the clinical course of stroke, functional outcomes and the value of oral anticoagulation (OAC) for secondary prevention according to AF subtype. Methods Acute ischemic stroke patients were consecutively enrolled and AF was classified as AFDAS or KAF. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) and 3‐month functional outcomes were measured on the modified Rankin scale. Inverse probability weighting was applied to adjust for baseline confounders in patients with AFDAS and KAF. Multivariate logistic regression models were calculated to investigate the value of OAC for secondary prevention. Results A total of 822 stroke patients with AF were included, of whom 234 patients (28.5%) had AFDAS. AFDAS patients had a lower prevalence of coronary artery disease, heart failure, and sustained AF, but higher rates of large vessel occlusion compared to KAF patients. NIHSS scores were lower in patients on pre‐stroke anticoagulation. OAC for secondary prevention was associated with favorable 3‐month functional outcome (odds ratio 7.60, 95% confidence interval 3.42–16.88) independently of AF subtype. The rate of stroke recurrence did not differ significantly. Conclusions Clinical characteristics suggest that AFDAS might comprise a distinct pathophysiological and clinical entity among stroke patients with AF. The benefit of anticoagulation for secondary prevention was not affected by AF subtype.