Supplementary Material for: Pre-Stroke CHADS<sub>2</sub> and CHA<sub>2</sub>DS<sub>2</sub>-VASc Scores Are Useful in Stratifying Three-Month Outcomes in Patients with and without Atrial Fibrillation

<b><i>Background:</i></b> CHADS<sub>2</sub> and CHA<sub>2</sub>DS<sub>2</sub>-VASc scores are validated tools for assessing stroke risk in patients with atrial fibrillation (AF). We investigated whether these scores are associated with 3-month stroke outcomes and evaluated the utility of these scores in stratifying 3-month stroke outcomes in both patients with and without AF. <b><i>Methods:</i></b> We analysed 6,612 acute ischaemic stroke patients from the Virtual International Stroke Trials Archive who received either placebo or ineffective active treatments not associated with significant cardiac complications. Outcomes included 3-month mortality, good functional outcomes defined as modified Rankin Scale score ≤1 and serious cardiac adverse events (SCAEs) defined as one of acute coronary syndrome, symptomatic heart failure, cardiopulmonary arrest, life-threatening arrhythmia and cardiac death. The association between the pre-stroke CHADS<sub>2</sub> and CHA<sub>2</sub>DS<sub>2</sub>-VASc scores and 3-month stroke outcomes was assessed using binary logistic regression. The utility of the two scores in estimating 3-month stroke outcomes was assessed using area under the receiver operator characteristic curves (AUC) and compared using the χ<sup>2</sup> test. <b><i>Results:</i></b> In this cohort, 26.5% had AF, 35.3% received IV tissue plasminogen activator (tPA), 17.7% died, 25.1% achieved good functional outcomes and 9.5% had ≥1 SCAE at 3 months. High-risk (≥2) pre-stroke CHADS<sub>2</sub> and CHA<sub>2</sub>DS<sub>2</sub>-VASc scores are both associated with 3-month mortality (CHADS<sub>2</sub>: odds ratio, OR, 2.33, 95% confidence interval 1.81-3.00; CHA<sub>2</sub>DS<sub>2</sub>-VASc: OR 3.01, 2.00-4.80), good functional outcomes (CHADS<sub>2</sub>: OR 0.47, 0.39-0.57; CHA<sub>2</sub>DS<sub>2</sub>-VASc: OR 0.55, 0.42-0.71) and SCAEs (CHADS<sub>2</sub>: OR 1.76, 1.28-2.42; CHA<sub>2</sub>DS<sub>2</sub>-VASc: OR 2.69, 1.53-4.73) after adjusting for baseline differences in neurological impairment, tPA use and AF. The pre-stroke CHA<sub>2</sub>DS<sub>2</sub>-VASc score is better than the CHADS<sub>2</sub> score in estimating 3-month stroke outcomes in both patients with and without AF (p ≤ 0.005 in all AUC comparisons). High-risk pre-stroke CHA<sub>2</sub>DS<sub>2</sub>-VASc score has high sensitivity for mortality (AF: 0.96, 0.94-0.98; no AF: 0.88, 0.86-0.91) and negative predictive value for SCAE (AF: 0.93, 0.87-0.96; no AF: 0.96, 0.95-0.97) within 3 months. Low risk pre-stroke CHA<sub>2</sub>DS<sub>2</sub>-VASc score has high specificity for good functional outcome (AF: 0.99, 0.98-0.994; no AF: 0.94, 0.93-0.95) at 3 months. <b><i>Conclusions:</i></b> The pre-stroke CHA<sub>2</sub>DS<sub>2</sub>-VASc score appears to be a simple tool for identifying patients at lower risk of poor outcomes and serious cardiac complications within 3 months following ischaemic stroke in patients with and without AF.