COVID-19 research briefs: hydroxychloroquine, chloroquine, azithromycin not associated with benefit and may increase harms

Daily POEMs

Published: 2020-05-30 © 2020 John Wiley & Sons, Inc.

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Clinical question
Can hydroxychloroquine, chloroquine, or azithromycin improve outcomes for patients with SARS-CoV-2 infection?

Bottom line
Hydroxychloroquine (HCQ), chloroquine, and azithromycin, used alone or in combination, do not reduce mortality in patients with COVID-19 and increase the risk of serious cardiac-related adverse events. (LOE = 4)

Reference
Rosenberg ES, Dufort EM, Udo T, et al. Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York State. JAMA. Published online May 11, 2020. doi:10.1001/jama.2020.8630

Mehra MR, Desai SS, Ruschitzka F, Patel AN. Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Lancet. Published online May 22, 2020. doi:10.1016/S0140-6736(20)31180-6.

Study design: Cohort (retrospective)

Setting: Inpatient (any location)

Synopsis
Research Brief #26: These authors reviewed the records of 1438 patients hospitalized with COVID-19. These patients represented nearly 90% of all patients with COVID-19 hospitalized in the New York metropolitan region. The overall in-hospital mortality was 20.3%. In patients who were given HCQ alone the mortality rate was 19.9%; in those given HCQ plus azithromycin, the mortality was 25.7%; in patients only given azithromycin, 10%; and in those given neither HCQ nor azithromycin, 12.7%. After taking into account other factors associated with in-hospital mortality, the authors found no association with either drug alone or in combination and decreased hospital mortality. They also found, however, that patients who were given the combination of HCQ plus azithromycin were twice as likely to suffer a cardiac arrest (adjusted odds ratio 2.13; 95% CI 1.12 - 4.05), while there was no similar increase in risk for patients taking either drug alone. Rosenberg ES, Dufort EM, Udo T, et al. Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York State. JAMA. Published online May 11, 2020. doi:10.1001/jama.2020.8630 Research Brief #27: These authors reviewed registry data from 96,032 patients hospitalized with COVID-19 in 1 of 627 hospitals on 6 continents. Since they were not part of a formal protocol, the treatment choices by the treating clinicians were quite varied: 1868 patients received chloroquine; 3783 received chloroquine plus a macrolide; 3016 received HCQ; 6221 received HCQ plus a macrolide; and 81,144 (84.4%) received none of these agents. Of these patients, 11% died while in the hospital. Although there was no significant difference in the proportion of patients with baseline sepsis-related organ failure assessment scores of less than 1 (80% to 83% of patients in each treatment group), patients who received one of these agents were minimally more likely to have oxygen saturation less than 94% (9.5% for control patients compared with 10.5% to 11.2% of the rest). The researchers were unable to find that the use of any of these agents was associated with any improved outcomes. On the contrary, they identified their use to be associated with significant harms. In-hospital mortality in the control patients was 9.3%, 16.4% for those taking chloroquine, 22.2% for those taking chloroquine plus a macrolide, 18.0% for those taking HCQ, and 23.8% for those taking HCQ plus a macrolide. Very few (0.3%) of the control patients developed a new ventricular arrhythmia compared with 4.3% of the patients taking chloroquine, 6.5% of those taking chloroquine plus a macrolide, 6.1% of those taking HCQ, and 8.1% of those taking HCQ plus a macrolide. Finally, after adjusting for several factors associated with outcomes, the probability of being harmed was significantly greater with any of these interventions. Mehra MR, Desai SS, Ruschitzka F, Patel AN. Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Lancet. Published online May 22, 2020. doi:10.1016/S0140-6736(20)31180-6. IMPORTANT NOTE: In light of the significant safety concerns, the overwhelming number of studies that fail to demonstrate any benefit, and the recent suspension of randomized trials, the POEMs authors have decided not to cover other studies of hydroxychloroquine or chloroquine until such time that there is evidence of benefit.

Henry C. Barry, MD, MS
Professor
Michigan State University
East Lansing, MI

Copyright © 2020 John Wiley & Sons, Inc.