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)
Mercuro et al.
, Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant..
, JAMA Cardiol., May 1, 2020, doi:10.1001/jamacardio.2020.1834
Study of 90 hospitalized patients given HCQ, 53 also receiving AZ, 53% hypertension, 29% diabetes mellitus, baseline median QTc 473ms for HCQ, and 442ms for HCQ+AZ. Median change for HCQ+AZ ΔQTc of 23ms vs. 5.5ms for HCQ. Other factors such as stress cardiomyopathy or myocarditis could not be ruled out. Without a control arm, they could not conclude that HCQ and AZ conferred increased cardiotoxic risk; however, compared with HCQ alone, ΔQTc differences were likely associated with the addition of AZ. The likelihood of prolonged QTc was greater in those who received concomitant loop diuretics or had a baseline QTc of 450 milliseconds or more. HCQ was discontinued in 10 patients due to adverse events including nausea, hypoglycemia, and 1 case of torsades de pointes. There were no deaths reported.
Appropriate use and careful analysis of contraindications, risks, and benefits are important. More recent and much larger studies have not shown significant safety concerns, including outpatient RCTs showing no serious adverse events, and even the RECOVERY trial which used an unusually high dose of HCQ (including 237 patients also receiving AZ) reports they "did not show any excess in ventricular tachycardia (including torsade de pointes) or ventricular fibrillation in the hydroxychloroquine arm", and "serious cardiovascular toxicity has been reported very rarely despite the high prevalence of cardiovascular disease in hospitalized patients, the common occurrence of myocarditis in COVID-19, and the extensive use of hydroxychloroquine and azithromycin together."
Mercuro et al., 1 May 2020, peer-reviewed, 7 authors.
JAMA Cardiology | Brief Report
Risk of QT Interval Prolongation Associated With Use
of Hydroxychloroquine With or Without Concomitant Azithromycin
Among Hospitalized Patients Testing Positive for Coronavirus Disease
Nicholas J. Mercuro, PharmD, BCIDP; Christina F. Yen, MD; David J. Shim, MD, PhD; Timothy R. Maher, MD;
Christopher M. McCoy, PharmD, BCPS(AQ-ID), BCIDP; Peter J. Zimetbaum, MD; Howard S. Gold, MD
Editorial page 986
IMPORTANCE Administration of hydroxychloroquine with or without azithromycin for the
Related article page 1067
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
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
CONCLUSIONS AND RELEVANCE In this cohort study, patients who received hydroxychloro-
quine 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
JAMA Cardiol. 2020;5(9):1036-1041...
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