How Often Do QT-prolonging Drugs Really Prolong QT? A Systematic Review

To systematically evaluate the incidence and prevalence of drug-induced QT interval prolongation and torsades de pointes (TdP) among adults exposed to QT-prolonging medications.

Systematic review of observational and interventional studies identified through MEDLINE (via PubMed).

Primary and secondary care settings, including inpatient and outpatient populations, across multiple geographical regions.

Adult patients (18 years and older) receiving QT-prolonging drugs and undergoing electrocardiographic monitoring. Studies reporting QTc prolongation using predefined thresholds were eligible. A total of 14,756 participants were included across 42 studies.

Exposure to QT-prolonging medications.

The primary outcome was the incidence or prevalence of significant QTc prolongation, defined as QTc >500 ms or an increase in QTc (ΔQTc) ≥60 ms. The secondary outcome was the occurrence of TdP.

Of 501 records, 42 studies met the inclusion criteria: 5 were interventional and 37 observational, involving a total of 14,756 patients. Methadone was the most frequently studied drug (17 studies), with reported QTc >500 ms incidence ranging from 0% to 16.2%, and TdP prevalence up to 3.6% and incidence of up to 3.2%. Other frequently studied drugs included hydroxychloroquine (5 studies), azithromycin (4 studies), and antipsychotics such as haloperidol and quetiapine. Incidence of QTc >500 ms varied considerably across settings and drug classes, influenced by heterogeneous QTc correction formulas.

Drug-induced QTc prolongation is not uncommon across a range of widely used medications, especially in psychiatric care, yet its monitoring and risk remain inconsistently assessed, particularly in outpatient settings. While TdP was rarely reported, QTc >500 ms occurred with notable frequency. Significant heterogeneity in QTc definitions, study populations, and ECG methodologies limits cross-study comparability, underscoring the need for greater standardization.