The Impact of QT‐Prolonging Medications and Drug–Drug Interactions on QTc Interval Prolongation in Hospitalized Patients: A Case‐Crossover Study

Researchers have studied potential corrected QT interval (QTc) prolongation from drug-drug interactions (DDIs), raising unresolved questions about their real-world impact. This retrospective case-crossover study investigated the effects of QT-prolonging drugs and DDIs on QTc prolongation in hospitalized patients aged 45 years and above. The cohort comprised patients who had multiple hospitalizations and developed QTc prolongation (QTc > 500 ms or an increase of >60 ms from baseline) at least 24 hours after admission between 2011 and 2019. Conditional logistic regression compared drug exposure between hospitalizations with QTc prolongation (case window) and those without (reference window). Among 2,276 patients (mean age 71; 43.8% female), the use of QT-prolonging drugs significantly increased the risk of QTc prolongation (odds ratio: 2.42 (95% confidence interval: 1.95-3.02)). The risk was higher with drugs of "known risks" (OR: 3.78 (2.91-4.90)) and "conditional risk" (OR: 2.08 (1.65-2.62)). DDIs, particularly involving multiple "known risk" drugs (OR: 7.86 (4.96-12.45)), strong cytochrome P450 enzyme inhibitors (OR: 5.57 (2.75-11.30)), or the concurrent use of ≥4 QT-prolonging drugs with any risk (OR: 5.28 (3.96-7.03)) substantially increased the risk. Cautious prescribing for patients with multiple risk factors is important to minimize the likelihood of QTc prolongation. However, when considering enhanced monitoring or drug choices, it is crucial to carefully evaluate the overall risk of QT prolongation against the benefits of treatment to ensure optimal patient care.