Baseline Antithrombotic Therapy and Intracranial Hemorrhage Risk in Infective Endocarditis: A Multicenter Prospective Cohort Study

BACKGROUND: Infective endocarditis (IE) carries high morbidity and mortality, largely from neurological complications. The clinical significance of chronic antithrombotic therapy remains uncertain. We assessed whether baseline antithrombotic therapy influences intracranial hemorrhage (ICH) and mortality in left-sided IE. METHODS: We analyzed a prospective multicenter cohort (2008-2018) including all patients with definite left-sided IE. Patients were classified at diagnosis as receiving no therapy (NT), antiplatelet therapy (APT), anticoagulation (AC), or combined therapy (CAT). The primary outcome was 30-day ICH; secondary outcomes included ischemic stroke, embolic events, major bleeding, and all-cause mortality. Multivariable logistic and Cox regression models adjusted for confounders. RESULTS: Among 3236 patients, 182 (5.6%) developed ICH, with the highest incidence in CAT (9.5%) and AC (6.8%). Compared with NT, baseline AC was independently associated with a higher frequency of ICH (adjusted risk ratio [aRR] 1.83, 95% CI 1.16-2.91), with the highest risk observed in CAT (aRR 2.45, 95% CI 1.55-3.87). Antiplatelet therapy was not associated with ICH. Ischemic stroke rates were similar across groups. Combined anticoagulation and antiplatelet therapy independently predicted higher 1-year mortality (adjusted hazard ratio [aHR] 1.21, 95% CI 1.02-1.43). Independent factors associated with ICH were Staphylococcus aureus and Candida spp. IE, extracranial embolism, prior cerebrovascular disease, and septic shock. CONCLUSIONS: These findings highlight the value of baseline antithrombotic exposure, together with microbiologic etiology and prior cerebrovascular disease, for early neurologic risk stratification at the time of IE diagnosis, informing neuroimaging decisions and multidisciplinary discussions involving infectious diseases specialists, neurologist, and cardiac surgeons among other specialists.