IntroductionDrug-induced QT interval prolongation is a well-recognized safety concern in hospitalized patients. Clinical decision support systems (CDSS) generate alerts to identify high-risk drug combinations, but their impact on clinical management remains uncertain.MethodsThis study evaluated clinical responses from prescribing clinicians to QT prolongation alerts, focusing on electrocardiogram (ECG) monitoring and treatment modifications. We conducted a 10-month prospective study in two hospital wards (acute geriatrics and orthopedics) at Geneva University Hospitals. The CDSS embedded within the electronic health record used a pharmacodynamic risk scoring system (Riskbase) that assigns scores to individual drugs based on pharmacological and clinical evidence and generates alerts when cumulative risk exceeds a predefined threshold. Clinical interventions were assessed within 7 days following high-risk QT alerts.ResultsA total of 154 patients were included (123 in geriatrics and 31 in orthopedics). Intervention rates ranged from 60.2% to 91.9% in geriatrics and from 45.2% to 80.6% in orthopedics, depending on the time window. However, these interventions were almost exclusively driven by ECG monitoring. Treatment modifications were rare, occurring in only 2.0% of patients. Most alerts were associated with combinations of low- or moderate-risk drugs, particularly antipsychotics, antidepressants, and antiemetics, some of which may have alternatives with lower QT-prolongation potential and may be considered depending on the clinical context. In addition, medications prescribed on an as-needed basis contributed substantially to QT risk scores, despite limited recent administration.DiscussionIn clinical practice, QT prolongation alerts are associated with frequent monitoring but rarely lead to therapeutic changes. These findings highlight a gap between risk identification and pharmacological risk mitigation and suggest opportunities to improve medication safety through more targeted prescribing and optimization of alert systems.