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

Abstract

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.

Hydroxychloroquine and the associated risk of arrhythmias

“…Additionally, by examining health records from the Cerner Health Facts ® database, which contains data from over 60 million patients, the study found a link between HCQ and a moderate increase in QTc interval compared to those who took sulfasalazine or methotrexate 1 . When HCQ was used alone, the average QTc measurement before the index timestamp (a specific time point) was 428.15 ms. After the index timestamp was reached, it increased to 446.18 ms.…”

“…Additionally, a comprehensive analysis of de-identified patient health records indicated that HCQ was associated with a moderate increase in the QTc interval compared to individuals exposed to sulfasalazine or methotrexate 1 . However, no further enhancement of the QTc interval was observed when HCQ was used concomitantly with other drugs known to increase the QTc interval.…”

“…HCQ is believed to cause arrhythmia by slowing the rate of action potential firing in the sinoatrial (SA) node. This could be explained by the structural similarity between HCQ and class IA anti-arrhythmic quinidine, which specifically blocks sodium and potassium channels, leading to prolongation of the QT interval and increasing the risk of Torsades de Pointes (TdP) 1 , 2 , 3 , 4 , 5 . However, conflicting data are available.…”

Hydroxychloroquine and Chloroquine-Induced Cardiac Arrhythmias and Sudden Cardiac Death in Patients With Systemic Autoimmune Rheumatic Diseases: A Systematic Review and Meta-Analysis

“…These 7 studies also only included HCQ users. 21,22,36,43,44,49,50 Thirteen studies (38.2%) were pre-COVID-19 studies, and 6 were published following the publication of the American College of Rheumatology's white paper on potential cardiac effects of HCQ and CQ. 3…”

Hydroxychloroquine, QTc prolongation and risk of torsades de pointes

“…A retrospective study categorized patients into six cohorts based on exposure to hydroxychloroquine, methotrexate, or sulfasalazine alone, or the combination of any of those drugs with any concomitant drug known to prolong the QT interval. A statistically significant increase in QTc interval of 18.0 ms (95% CI: 3.5–32.5; p < 0.05) was found in the hydroxychloroquine monotherapy cohort [ 25 ].…”