Non-vitamin K-dependent Oral Anticoagulants Have a Positive Impact on Ischaemic Stroke Severity in Patients With Atrial Fibrillation

Simon Hellwig; Ulrike Grittner; Heinrich Audebert; Matthias Endres; Karl Georg Haeusler


Europace. 2018;20(4):569-574. 

In This Article


Study Design

This single-centre observational study was conducted at the Department of Neurology, Charité - Universitätsmedizin Berlin and approved by the local Ethics Committee (EA2/022/15). Medical records of 3669 patients consecutively admitted to the stroke unit of the Department of Neurology, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, between 1 January 2013 and 31 December 2015 were retrospectively analysed. Patients suffering an ischaemic stroke or transient ischaemic attack (TIA) (labeled as 'index stroke') were identified by using relevant ICD-10 discharge diagnoses (I63.x; G45.x). All patients with ischaemic stroke or TIA and known AF before admission for their index stroke were included in the primary analysis. We did not include patients suffering from haemorrhagic stroke. The following information was assessed from medical records: demographic details, cardiovascular risk factors (e.g. atrial fibrillation, congestive heart failure, hypertension, diabetes mellitus, previous stroke or TIA, intracerebral haemorrhage or non-stroke vascular events), potential contraindications for oral anticoagulation (such as malignant tumours or epilepsy), CHA2DS2-VASc score before the index stroke, antithrombotic medication before admission, INR on admission, thrombin time, activated partial thromboplastin time (aPTT), iv thrombolysis or mechanical intervention, diagnostic results during the hospital stay (echocardiography, ultrasound of the brain-supplying arteries, brain imaging), stroke severity on admission according to the National Institutes of Health Stroke Scale (NIHSS) score as well as functional outcome at hospital discharge according to the modified Rankin Scale (mRS).[16–18] Severe stroke was defined as NIHSS ≥ 11 points.[8] Poor functional outcome was defined as mRS > 2 at hospital discharge.

Statistical Analysis

The results are reported as frequencies and percentages for categorical variables. In the case of continuous variables, mean and standard deviation (SD) are reported for sufficiently normally distributed data (|skewness| < 1) or median and inter-quartile range (IQR) for quantitatively skewed variables. Differences regarding baseline parameters between patients with different pre-stroke antithrombotic medication were tested using either χ2, Fisher's exact test, or Student's t-test for independent samples (Table 1). First, we tested overall differences between six cohorts using χ2 test or one-way ANOVA (for age). In case of P ≤ 0.1, we performed post-hoc exploratory tests for the NOAC cohort vs. other cohorts. A two sided significance-level of α = 0.05 was applied. Severe stroke (NIHSS ≥ 11) and poor functional outcome (mRS > 2) were the main outcomes. P-values testing different characteristics with regard to these outcomes were age-adjusted using binary logistic regression models (Supplementary material online, Table S2). In multiple logistic regression, associations between antithrombotic treatment and stroke severity at admission and functional outcome at discharge were tested after adjustment for age, sex, diabetes mellitus, previous stroke, coronary artery disease, congestive heart failure, peripheral artery disease, renal insufficiency, epilepsy, and malignant tumour (Table 2). In addition, endovascular treatment was added to the model regarding the functional outcome at hospital discharge. Stroke severity and iv thrombolysis however are affected by oral anticoagulation at stroke onset and have an impact on functional outcome. Instead of being mere confounders, they are factors on the 'causal pathway' from anticoagulation treatment to functional outcome at discharge and cannot simply be adjusted for in multiple regression analysis.[19] Therefore, we performed a structural equation analysis to evaluate the causal relationship between anticoagulatory treatment, NIHSS score on admission as well as iv thrombolysis and functional outcome at hospital discharge (Supplementary material online, Figure S1). Odds ratios (OR) with 95% confidence intervals (CI) are reported. Despite of comparably small groups, we performed a sensitivity analysis comparing NOAC patients with or without altered routine anticoagulation tests to those patients without medical stroke prevention. Data were analysed using SPSS statistics 23 and SPSS AMOS 24 (IBM Corp., Armonk, NY, USA).

Figure S1.

Structural equation modeling for mRS ≥3 at hospital discharge in 655 stroke patients, additionally adjusted for age, sex, co-existing diabetes mellitus, previous stroke, coronary artery disease, congestive heart failure, peripheral artery disease, renal insufficiency, epilepsy, malignant tumor (data not shown). Standardized estimates (AMOS SPSS IBM).