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ImportanceThe European Society of Cardiology (ESC) 0/1-hour algorithm is a validated high-sensitivity cardiac troponin (hs-cTn) protocol for emergency department patients with possible acute coronary syndrome. However, limited data exist regarding its performance in patients with known coronary artery disease (CAD; prior myocardial infarction [MI], coronary revascularization, or ≥70% coronary stenosis).ObjectiveTo evaluate and compare the diagnostic performance of the ESC 0/1-hour algorithm for 30-day cardiac death or MI among patients with and without known CAD and determine if the algorithm could achieve the negative predictive value rule-out threshold of 99% or higher.Design, Setting, and ParticipantsThis was a preplanned subgroup analysis of the STOP-CP prospective multisite cohort study, which was conducted from January 25, 2017, through September 6, 2018, at 8 emergency departments in the US. Patients 21 years or older with symptoms suggestive of acute coronary syndrome without ST-segment elevation on initial electrocardiogram were included. Analysis took place between February and December 2022.Interventions/ExposuresParticipants with 0- and 1-hour high-sensitivity cardiac troponin T (hs-cTnT) measures were stratified into rule-out, observation, and rule-in zones using the ESC 0/1-hour hs-cTnT algorithm.Main Outcomes and MeasuresCardiac death or MI at 30 days determined by expert adjudicators.ResultsDuring the study period, 1430 patients were accrued. In the cohort, 775 individuals (54.2%) were male, 826 (57.8%) were White, and the mean (SD) age was 57.6 (12.8) years. At 30 days, cardiac death or MI occurred in 183 participants (12.8%). Known CAD was present in 449 (31.4%). Among patients with known CAD, the ESC 0/1-hour algorithm classified 178 of 449 (39.6%) into the rule-out zone compared with 648 of 981 (66.1%) without CAD (P P P = .04).Conclusions and RelevanceAmong patients with known CAD, the ESC 0/1-hour hs-cTnT algorithm was unable to safely exclude 30-day cardiac death or MI. This suggests that clinicians should be cautious if using the algorithm in patients with known CAD. The negative predictive value was significantly higher in patients without a history of CAD but remained less than 99%.