Abstract

Risk factors for ischemic stroke broadly overlap with predictors of atherosclerotic vascular disease. Few studies have examined this risk in patients with different types of symptomatic atherosclerotic disease. Methods: TRA 2°P-TIMI 50 was a multinational, randomized, trial of 26449 patients with atherothrombosis randomized to vorapaxar or placebo added to standard therapy. Patients qualified with a history of myocardial infarction (MI), symptomatic peripheral arterial disease (PAD), or recent ischemic stroke (CVD, 2 wks to 12 mo.). Stroke was adjudicated by an independent CEC. Correlates of stroke were determined in placebo patients (N=13,169) Results: A total of 294 ischemic strokes occurred during follow up. Overall age, hypertension, diabetes mellitus, PAD, prior ischemic stroke, renal dysfunction, atrial fibrillation/flutter, and carotid stenosis ≥ 50% were associated with new ischemic stroke during follow up (Figure A). After adjustment age, hypertension, diabetes, prior ischemic stroke, and atrial fibrillation/flutter remained significantly associated with ischemic stroke with a history of ischemic stroke associated with the greatest hazard (adj HR 5.15, 95% CI 4.02 - 6.61, p<0.001). When stratified by qualifying event, traditional risk factors and distant ischemic stroke were associated with new stroke in the MI/PAD group (Figure B). In contrast, only diabetes and prior myocardial infarction were associated with recurrent stroke in the CVD group (Figure C). Conclusions: Predictors of ischemic stroke in patients with atherosclerotic vascular disease vary by the primary symptomatic bed. In patients with recent MI or PAD, prior stroke is the strongest predictor while traditional risk factors are also associated with recurrent events. In patients with recent stroke only prior MI and diabetes predict recurrent stroke.

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