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Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State

Educational Objective
To understand how treatment with Hydroxychloroquine or Azithromycin may affect In-Hospital Mortality in Patients with COVID-19
1 Credit CME
Key Points

Question  Among patients with coronavirus disease 2019 (COVID-19), is there an association between use of hydroxychloroquine, with or without azithromycin, and in-hospital mortality?

Findings  In a retrospective cohort study of 1438 patients hospitalized in metropolitan New York, compared with treatment with neither drug, the adjusted hazard ratio for in-hospital mortality for treatment with hydroxychloroquine alone was 1.08, for azithromycin alone was 0.56, and for combined hydroxychloroquine and azithromycin was 1.35. None of these hazard ratios were statistically significant.

Meaning  Among patients hospitalized with COVID-19, treatment with hydroxychloroquine, azithromycin, or both was not associated with significantly lower in-hospital mortality.

Abstract

Importance  Hydroxychloroquine, with or without azithromycin, has been considered as a possible therapeutic agent for patients with coronavirus disease 2019 (COVID-19). However, there are limited data on efficacy and associated adverse events.

Objective  To describe the association between use of hydroxychloroquine, with or without azithromycin, and clinical outcomes among hospital inpatients diagnosed with COVID-19.

Design, Setting, and Participants  Retrospective multicenter cohort study of patients from a random sample of all admitted patients with laboratory-confirmed COVID-19 in 25 hospitals, representing 88.2% of patients with COVID-19 in the New York metropolitan region. Eligible patients were admitted for at least 24 hours between March 15 and 28, 2020. Medications, preexisting conditions, clinical measures on admission, outcomes, and adverse events were abstracted from medical records. The date of final follow-up was April 24, 2020.

Exposures  Receipt of both hydroxychloroquine and azithromycin, hydroxychloroquine alone, azithromycin alone, or neither.

Main Outcomes and Measures  Primary outcome was in-hospital mortality. Secondary outcomes were cardiac arrest and abnormal electrocardiogram findings (arrhythmia or QT prolongation).

Results  Among 1438 hospitalized patients with a diagnosis of COVID-19 (858 [59.7%] male, median age, 63 years), those receiving hydroxychloroquine, azithromycin, or both were more likely than those not receiving either drug to have diabetes, respiratory rate >22/min, abnormal chest imaging findings, O2 saturation lower than 90%, and aspartate aminotransferase greater than 40 U/L. Overall in-hospital mortality was 20.3% (95% CI, 18.2%-22.4%). The probability of death for patients receiving hydroxychloroquine + azithromycin was 189/735 (25.7% [95% CI, 22.3%-28.9%]), hydroxychloroquine alone, 54/271 (19.9% [95% CI, 15.2%-24.7%]), azithromycin alone, 21/211 (10.0% [95% CI, 5.9%-14.0%]), and neither drug, 28/221 (12.7% [95% CI, 8.3%-17.1%]). In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in mortality for patients receiving hydroxychloroquine + azithromycin (HR, 1.35 [95% CI, 0.76-2.40]), hydroxychloroquine alone (HR, 1.08 [95% CI, 0.63-1.85]), or azithromycin alone (HR, 0.56 [95% CI, 0.26-1.21]). In logistic models, compared with patients receiving neither drug cardiac arrest was significantly more likely in patients receiving hydroxychloroquine + azithromycin (adjusted OR, 2.13 [95% CI, 1.12-4.05]), but not hydroxychloroquine alone (adjusted OR, 1.91 [95% CI, 0.96-3.81]) or azithromycin alone (adjusted OR, 0.64 [95% CI, 0.27-1.56]), . In adjusted logistic regression models, there were no significant differences in the relative likelihood of abnormal electrocardiogram findings.

Conclusions and Relevance  Among patients hospitalized in metropolitan New York with COVID-19, treatment with hydroxychloroquine, azithromycin, or both, compared with neither treatment, was not significantly associated with differences in in-hospital mortality. However, the interpretation of these findings may be limited by the observational design.

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Article Information

Corresponding Author: Eli S. Rosenberg, PhD, Department of Epidemiology and Biostatistics, University at Albany School of Public Health, One University Pl, Room 123, Albany, NY 12203 (erosenberg2@albany.edu).

Published Online: May 11, 2020. doi:10.1001/jama.2020.8630

Author Contributions: Dr Rosenberg had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Rosenberg, Dufort, Udo, Wilberschied, Kumar, Kirkwood, DeHovitz, Blog, Hutton, Holtgrave, Zucker.

Acquisition, analysis, or interpretation of data: Rosenberg, Dufort, Udo, Wilberschied, Kumar, Tesoriero, Weinberg, Kirkwood, Muse, DeHovitz, Blog, Holtgrave.

Drafting of the manuscript: Rosenberg, Dufort, Udo, Wilberschied, Kumar, Blog, Holtgrave.

Critical revision of the manuscript for important intellectual content: Rosenberg, Dufort, Udo, Wilberschied, Kumar, Tesoriero, Weinberg, Kirkwood, Muse, DeHovitz, Hutton, Holtgrave, Zucker.

Statistical analysis: Rosenberg, Udo, Wilberschied, Kumar, Holtgrave.

Obtained funding: Dufort, Tesoriero.

Administrative, technical, or material support: All authors.

Supervision: Rosenberg, Dufort, Weinberg, Blog, Hutton, Holtgrave.

Conflict of Interest Disclosures: Dr Dufort reported that her spouse has a Gilead Foundation-Focus HIV/HCV testing research grant. No other disclosures were reported.

Additional Contributions: The authors wish to acknowledge the following contributors to this work, who did not receive any specific compensation for their contributions. From IPRO: Wendy Ferguson, DipED, Allison Xiong, PhD, Matthew Roberts, DrPH, Kathleen Terry, PhD, Lois Piper, MBA, as well as the nursing and analytical team. From University at Albany: Janine Jurkowski, PhD, and Kerianne Engesser, BS. From New York State Department of Health Emerging Infections Program: Jemma Rowlands, MPH, Grant Barney, MPH, Nancy Spina, MPH, Rachel Wester, MPH. From New York State Department of Health Office of Quality and Patient Safety: Meng Wu, PhD, and Deirdre Depew, ME. From New York State Department of Health AIDS Institute: Michelle Cummings, MS. From New York State Department of Health Center for Community Health: Thomas Justin II, BSc. From New York State Department of Health Office of Primary Care and Health Systems Management: Daniel McNamara, BSPharm, and Kimberly Leonard, BSPharm. From Albany College of Pharmacy and Health Sciences: Darren Grabe, PharmD. From New York University Langone Medical Center: Mark Mulligan, MD, Robert Ulrich, MD, and Ellie Carmody, MD. New York State Department of Health and University at Albany employees worked on this study as part of their duties. IPRO employees work under a standing contract with the State of New York to conduct medical record extraction duties and other tasks, and their medical record extraction work was done as part of that standing contract. No grants were awarded for this study to the University at Albany. No funding was provided to New York University Langone Medical Center for the consultation of Drs Mulligan, Ulrich, and Carmody on this study. No funding was provided to Albany College of Pharmacy and Health Sciences for the consultation of Dr Grabe.

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