Tags

Type your tag names separated by a space and hit enter

Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19).
JAMA Cardiol. 2020 Sep 01; 5(9):1036-1041.JC

Abstract

Importance

Administration of hydroxychloroquine with or without azithromycin for the treatment of coronavirus disease 2019 (COVID-19)-associated pneumonia carries increased risk of corrected QT (QTc) prolongation and cardiac arrhythmias.

Objective

To characterize the risk and degree of QT prolongation in patients with COVID-19 in association with their use of hydroxychloroquine with or without concomitant azithromycin.

Design, Setting, and Participants

This was a cohort study performed at an academic tertiary care center in Boston, Massachusetts, of patients hospitalized with at least 1 positive COVID-19 nasopharyngeal polymerase chain reaction test result and clinical findings consistent with pneumonia who received at least 1 day of hydroxychloroquine from March 1, 2020, through April 7, 2020.

Main Outcomes and Measures

Change in QT interval after receiving hydroxychloroquine with or without azithromycin; occurrence of other potential adverse drug events.

Results

Among 90 patients given hydroxychloroquine, 53 received concomitant azithromycin; 44 (48.9%) were female, and the mean (SD) body mass index was 31.5 (6.6). Hypertension (in 48 patients [53.3%]) and diabetes mellitus (in 26 patients [28.9%]) were the most common comorbid conditions. The overall median (interquartile range) baseline QTc was 455 (430-474) milliseconds (hydroxychloroquine, 473 [454-487] milliseconds vs hydroxychloroquine and azithromycin, 442 [427-461] milliseconds; P < .001). Those receiving concomitant azithromycin had a greater median (interquartile range) change in QT interval (23 [10-40] milliseconds) compared with those receiving hydroxychloroquine alone (5.5 [-15.5 to 34.25] milliseconds; P = .03). Seven patients (19%) who received hydroxychloroquine monotherapy developed prolonged QTc of 500 milliseconds or more, and 3 patients (8%) had a change in QTc of 60 milliseconds or more. Of those who received concomitant azithromycin, 11 of 53 (21%) had prolonged QTc of 500 milliseconds or more and 7 of 53 (13 %) had a change in QTc of 60 milliseconds or more. The likelihood of prolonged QTc was greater in those who received concomitant loop diuretics (adjusted odds ratio, 3.38 [95% CI, 1.03-11.08]) or had a baseline QTc of 450 milliseconds or more (adjusted odds ratio, 7.11 [95% CI, 1.75-28.87]). Ten patients had hydroxychloroquine discontinued early because of potential adverse drug events, including intractable nausea, hypoglycemia, and 1 case of torsades de pointes.

Conclusions and Relevance

In this cohort study, patients who received hydroxychloroquine for the treatment of pneumonia associated with COVID-19 were at high risk of QTc prolongation, and concurrent treatment with azithromycin was associated with greater changes in QTc. Clinicians should carefully weigh risks and benefits if considering hydroxychloroquine and azithromycin, with close monitoring of QTc and concomitant medication usage.

Authors+Show Affiliations

Department of Pharmacy, Beth Israel Deaconess Medical Center, Boston, Massachusetts.Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.Harvard-Thorndike Electrophysiology Institute, Division of Cardiovascular Medicine, Beth Israel Deaconess Medical, Boston, Massachusetts.Department of Pharmacy, Beth Israel Deaconess Medical Center, Boston, Massachusetts.Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. Harvard-Thorndike Electrophysiology Institute, Division of Cardiovascular Medicine, Beth Israel Deaconess Medical, Boston, Massachusetts.Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32936252

Citation

Mercuro, Nicholas J., et al. "Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19)." JAMA Cardiology, vol. 5, no. 9, 2020, pp. 1036-1041.
Mercuro NJ, Yen CF, Shim DJ, et al. Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020;5(9):1036-1041.
Mercuro, N. J., Yen, C. F., Shim, D. J., Maher, T. R., McCoy, C. M., Zimetbaum, P. J., & Gold, H. S. (2020). Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19). JAMA Cardiology, 5(9), 1036-1041. https://doi.org/10.1001/jamacardio.2020.1834
Mercuro NJ, et al. Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020 Sep 1;5(9):1036-1041. PubMed PMID: 32936252.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19). AU - Mercuro,Nicholas J, AU - Yen,Christina F, AU - Shim,David J, AU - Maher,Timothy R, AU - McCoy,Christopher M, AU - Zimetbaum,Peter J, AU - Gold,Howard S, PY - 2020/9/16/entrez PY - 2020/9/17/pubmed PY - 2020/10/2/medline SP - 1036 EP - 1041 JF - JAMA cardiology JO - JAMA Cardiol VL - 5 IS - 9 N2 - Importance: Administration of hydroxychloroquine with or without azithromycin for the treatment of coronavirus disease 2019 (COVID-19)-associated pneumonia carries increased risk of corrected QT (QTc) prolongation and cardiac arrhythmias. Objective: To characterize the risk and degree of QT prolongation in patients with COVID-19 in association with their use of hydroxychloroquine with or without concomitant azithromycin. Design, Setting, and Participants: This was a cohort study performed at an academic tertiary care center in Boston, Massachusetts, of patients hospitalized with at least 1 positive COVID-19 nasopharyngeal polymerase chain reaction test result and clinical findings consistent with pneumonia who received at least 1 day of hydroxychloroquine from March 1, 2020, through April 7, 2020. Main Outcomes and Measures: Change in QT interval after receiving hydroxychloroquine with or without azithromycin; occurrence of other potential adverse drug events. Results: Among 90 patients given hydroxychloroquine, 53 received concomitant azithromycin; 44 (48.9%) were female, and the mean (SD) body mass index was 31.5 (6.6). Hypertension (in 48 patients [53.3%]) and diabetes mellitus (in 26 patients [28.9%]) were the most common comorbid conditions. The overall median (interquartile range) baseline QTc was 455 (430-474) milliseconds (hydroxychloroquine, 473 [454-487] milliseconds vs hydroxychloroquine and azithromycin, 442 [427-461] milliseconds; P < .001). Those receiving concomitant azithromycin had a greater median (interquartile range) change in QT interval (23 [10-40] milliseconds) compared with those receiving hydroxychloroquine alone (5.5 [-15.5 to 34.25] milliseconds; P = .03). Seven patients (19%) who received hydroxychloroquine monotherapy developed prolonged QTc of 500 milliseconds or more, and 3 patients (8%) had a change in QTc of 60 milliseconds or more. Of those who received concomitant azithromycin, 11 of 53 (21%) had prolonged QTc of 500 milliseconds or more and 7 of 53 (13 %) had a change in QTc of 60 milliseconds or more. The likelihood of prolonged QTc was greater in those who received concomitant loop diuretics (adjusted odds ratio, 3.38 [95% CI, 1.03-11.08]) or had a baseline QTc of 450 milliseconds or more (adjusted odds ratio, 7.11 [95% CI, 1.75-28.87]). Ten patients had hydroxychloroquine discontinued early because of potential adverse drug events, including intractable nausea, hypoglycemia, and 1 case of torsades de pointes. Conclusions and Relevance: In this cohort study, patients who received hydroxychloroquine for the treatment of pneumonia associated with COVID-19 were at high risk of QTc prolongation, and concurrent treatment with azithromycin was associated with greater changes in QTc. Clinicians should carefully weigh risks and benefits if considering hydroxychloroquine and azithromycin, with close monitoring of QTc and concomitant medication usage. SN - 2380-6591 UR - https://www.unboundmedicine.com/medline/citation/32936252/Risk_of_QT_Interval_Prolongation_Associated_With_Use_of_Hydroxychloroquine_With_or_Without_Concomitant_Azithromycin_Among_Hospitalized_Patients_Testing_Positive_for_Coronavirus_Disease_2019__COVID_19__ L2 - https://jamanetwork.com/journals/jamacardiology/fullarticle/10.1001/jamacardio.2020.1834 DB - PRIME DP - Unbound Medicine ER -