BackgroundLower gastrointestinal bleeding (LGIB) is a common complication for patients with coronary artery disease (CAD) due to the use of antithrombotic medications. Limited data exist describing which patients are at increased risk for mortality. AimThis study aims to (i) determine whether patients on dual antiplatelet therapy (DAPT) or triple therapy are at higher risk of 90-day and 6-month mortality compared with patients on aspirin alone and (ii) evaluate risk factors for mortality in patients with CAD on antithrombotics hospitalized with LGIB. MethodsWe conducted a retrospective cohort study of patients hospitalized with LGIB and CAD while on aspirin at a single academic medical center from 2007 to 2015. Patients were identified using a validated, machine-learning algorithm and classified by use of aspirin, DAPT, or triple therapy. Univariate and multivariate Cox proportional hazards were used to determine mortality associated risk factors. ResultsSeven hundred sixteen patients were identified with LGIB and CAD. Four hundred seventy-two (65.9%) patients were on aspirin monotherapy, 179 (25%) on aspirin and thienopyridine (DAPT), and 65 (9.1%) on aspirin, thienopyridine, and systemic anticoagulant (triple therapy). On univariate analysis, triple therapy use was associated with increased risk of 90-day (hazard ratio [HR] 3.12, 95% confidence interval [CI] 1.52-5.92, P=0.003) and 6-month (HR 2.46, 95%CI 1.29-4.35, P=0.008) mortality. Holding anticoagulation was associated with higher mortality at 90days (HR 2.30, 95%CI 1.27-4.07, P=0.007). On multivariate analysis, after adjusting for confounding variables, the use of triple therapy remained associated with higher 90-day mortality (HR 3.23, 95%CI 1.56-6.16, P=0.003). ConclusionTriple therapy is associated with mortality at 90days and at 6months post discharge.