QTc Prolongation with the Use of Hydroxychloroquine and Concomitant Arrhythmogenic Medications: A Retrospective Study Using Electronic Health Records Data

Drugs Real World Outcomes. 2022 Sep;9(3):415-423. doi: 10.1007/s40801-022-00307-5. Epub 2022 Jun 5.


Introduction: Hydroxychloroquine can induce QT/QTc interval prolongation for some patients; however, little is known about its interactions with other QT-prolonging drugs.

Objective: The purpose of this retrospective electronic health records study was to evaluate changes in the QTc interval in patients taking hydroxychloroquine with or without concomitant QT-prolonging medications.

Methods: De-identified health records were obtained from the Cerner Health Facts® database. Variables of interest included demographics, diagnoses, clinical procedures, laboratory tests, and medications. Patients were categorized into six cohorts based on exposure to hydroxychloroquine, methotrexate, or sulfasalazine alone, or the combination of any those drugs with any concomitant drug known to prolong the QT interval. Tisdale QTc risk score was calculated for each patient cohort. Two-sample paired t-tests were used to test differences between the mean before and after QTc measurements within each group and ANOVA was used to test for significant differences across the cohort means.

Results: A statistically significant increase in QTc interval from the last measurement prior to concomitant exposure of 18.0 ms (95% CI 3.5-32.5; p < 0.05) was found in the hydroxychloroquine monotherapy cohort. QTc changes varied considerably across cohorts, with standard deviations ranging from 40.9 (hydroxychloroquine monotherapy) to 57.8 (hydroxychloroquine + sulfasalazine). There was no difference in QTc measurements among cohorts. The hydroxychloroquine + QTc-prolonging agent cohort had the highest average Tisdale Risk Score compared with those without concomitant exposure (p < 0.05).

Conclusion: Our analysis of retrospective electronic health records found hydroxychloroquine to be associated with a moderate increase in the QTc interval compared with sulfasalazine or methotrexate. However, the QTc was not significantly increased with concomitant exposure to other drugs known to increase QTc interval.