Background:There is a rising incidence of infective endocarditis-related stroke (IERS) in the United States attributed to the opioid epidemic. A contemporary epidemiologic description is necessary to understand the impact of the opioid epidemic on clinical characteristics of IERS. We describe and analyze trends in the demographics, risk factors, and clinical features of IERS.Methods:This is a retrospective cohort study within a biracial population of 1.3 million in the Greater Cincinnati/Northern Kentucky region. All hospitalized patients with hemorrhagic or ischemic stroke were identified and physician verified from the 2005, 2010, and 2015 calendar years using ICD-9 and -10 codes. IERS was defined as an acute stroke attributed to infective endocarditis meeting modified Duke Criteria for possible or definite endocarditis. Unadjusted comparison of demographics, risk factors, outcome, and clinical characteristics was performed between each study period for IERS and non-IERS. An adjusted model to compare trends used Cochran-Armitage test for categorical variables and a general linear model or a Kruskal-Wallis test for numerical variables. Examination for interaction of endocarditis status in trends was performed using a general linear or logistic model.Results:A total of 54 patients with IERS and 8204 without IERS were identified during the study periods. Between 2005 and 2015, there was a decline in rates of hypertension (91.7% vs 36.0%; p=0.0005) and increased intravenous drug users (IVDU) (8.3% vs 44.0%; p=0.02) in the IERS cohort. The remainder of the stroke population demonstrated a significant rise in hypertension, diabetes, atrial fibrillation, and peri-operative stroke. Infective endocarditis status significantly interacted with the trend in hypertension prevalence (p=0.001).Conclusion:From 2005 to 2015, infective endocarditis-related stroke was increasingly associated with intravenous drug use and fewer risk factors, specifically hypertension. These trends likely reflect the demographics of the opioid epidemic, which has affected younger patients with fewer comorbidities.Non-standard Abbreviations and AcronymsIERS:infective endocarditis-related stroke; IVDU: intravenous drug users; GCNKSS: Greater Cincinnati Northern Kentucky Stroke Study; NIHSS: National Institute of Health Stroke Scale; tPA: tissue plasminogen activator