Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State | Cardiology | JN Learning | AMA Ed Hub [Skip to Content]
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Antibiotic Use, Overuse, Resistance, Stewardship

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
JAMA
June 23, 2020
Original Investigation
Eli S. Rosenberg, PhD1;
Elizabeth M. Dufort, MD2;
Tomoko Udo, PhD1;
Larissa A. Wilberschied, MS2;
Jessica Kumar, DO2;
James Tesoriero, PhD2;
Patti Weinberg, PA3;
James Kirkwood, MPH2;
Alison Muse, MPH2;
Jack DeHovitz, MD3,4;
Debra S. Blog, MD2;
Brad Hutton, MPH2;
David R. Holtgrave, PhD1;
Howard A. Zucker, MD2
Author Affiliations
  • 1University at Albany School of Public Health, State University of New York, Rensselaer
  • 2New York State Department of Health, Albany
  • 3IPRO, Lake Success, New York
  • 4Downstate Health Sciences University, State University of New York, Brooklyn
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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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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

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Cardiology Infectious Diseases Pulmonary Medicine Antibiotic Use, Overuse, Resistance, Stewardship Coronavirus (COVID-19)
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.

References
1.
Wang  C , Horby  PW , Hayden  FG , Gao  GF .  A novel coronavirus outbreak of global health concern.   Lancet. 2020;395(10223):470-473. doi:10.1016/S0140-6736(20)30185-9 PubMedGoogle ScholarCrossref
2.
The Center for Systems Science and Engineering at Johns Hopkins University. COVID-19 dashboard. 2020. Accessed March 24, 2020. https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd402994234 67b48e9ecf6
3.
Rosenberg  ES , Dufort  EM , Blog  DS ,  et al.  COVID-19 testing, epidemic features, hospital outcomes, and household prevalence, New York State—March 2020.   Clin Infect Dis. Published online May 8, 2020. doi:10.1093/cid/ciaa549Google Scholar
4.
New York State Department of Health. COVID-19 Tracker. 2020. Accessed May 7, 2020. https://covid19tracker.health.ny.gov/views/NYS-COVID19-Tracker/NYSDOHCOVID-19Tracker-Map?%3Aembed=yes&%3Atoolbar=no&%3Atabs=n
5.
Liu  J , Cao  R , Xu  M ,  et al.  Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro.   Cell Discov. 2020;6(1):16. doi:10.1038/s41421-020-0156-0 PubMedGoogle ScholarCrossref
6.
Yao  X , Ye  F , Zhang  M ,  et al.  In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).   Clin Infect Dis. 2020;ciaa237. doi:10.1093/cid/ciaa237 PubMedGoogle Scholar
7.
Colson  P , Rolain  JM , Lagier  JC , Brouqui  P , Raoult  D .  Chloroquine and hydroxychloroquine as available weapons to fight COVID-19.   Int J Antimicrob Agents. 2020;55(4):105932. doi:10.1016/j.ijantimicag.2020.105932 PubMedGoogle Scholar
8.
Gautret  P , Lagier  JC , Parola  P ,  et al.  Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial.   Int J Antimicrob Agents. 2020:105949. doi:10.1016/j.ijantimicag.2020.105949 PubMedGoogle Scholar
9.
Chen  Z , Hu  J , Zhang  Z ,  et al Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial. medRxiv. Preprint posted April 10, 2020. doi:10.1101/2020.03.22.20040758
10.
McGhie  TK , Harvey  P , Su  J , Anderson  N , Tomlinson  G , Touma  Z .  Electrocardiogram abnormalities related to anti-malarials in systemic lupus erythematosus.   Clin Exp Rheumatol. 2018;36(4):545-551.PubMedGoogle Scholar
11.
Hung  YM , Wang  YH , Lin  L , Wang  PYP , Chiou  JY , Wei  JC .  Hydroxychloroquine may be associated with reduced risk of coronary artery diseases in patients with rheumatoid arthritis: A nationwide population-based cohort study.   Int J Clin Pract. 2018;72(5):e13095. doi:10.1111/ijcp.13095 PubMedGoogle Scholar
12.
Chorin  E , Dai  M , Shulman  E ,  et al.  The QT interval in patients with COVID-19 treated with hydroxychloroquine and azithromycin.   Nat Med. Published online April 24, 2020. doi:10.1038/s41591-020-0888-2Google Scholar
13.
Borba  MGS , Val  FFA , Sampaio  VS ,  et al  Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial.   JAMA Netw Open. 2020;3(4):e208857. doi:10.1001/jamanetworkopen.2020.8857 Google Scholar
14.
FDA. Fact sheet for health care providers: emergency use authorization (EUA) of hydroxychloroquine sulfate supplied from the strategic national stockpile for treatment of COVID-19 in certain hospitalized patients. Posted April 27, 2020. Accessed May 7, 2020. https://www.fda.gov/media/136537/download
15.
Garg  S , Kim  L , Whitaker  M ,  et al.  Hospitalization rates and characteristics of patients hospitalized with laboratory-confirmed coronavirus disease 2019 - COVID-NET, 14 States, March 1-30, 2020.   MMWR Morb Mortal Wkly Rep. 2020;69(15):458-464. doi:10.15585/mmwr.mm6915e3 PubMedGoogle ScholarCrossref
16.
CDC COVID-19 Response Team.  Preliminary estimates of the prevalence of selected underlying health conditions among patients with coronavirus disease 2019 - United States, February 12-March 28, 2020.   MMWR Morb Mortal Wkly Rep. 2020;69(13):382-386. doi:10.15585/mmwr.mm6913e2 PubMedGoogle ScholarCrossref
17.
Magagnoli  J , Narendran  S , Pereira  F ,  et al Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19. medRxiv. Preprint posted April 23, 2020. doi:10.1101/2020.04.16.20065920
18.
Goyal  P , Choi  JJ , Pinheiro  LC ,  et al.  Clinical characteristics of Covid-19 in New York City.   N Engl J Med. Published online April 17, 2020. doi:10.1056/NEJMc2010419 PubMedGoogle Scholar
19.
Petrilli  CM , Jones  SA , Yang  J ,  et al Factors associated with hospitalization and critical illness among 4,103 patients with COVID-19 disease in New York City. medRxiv. Preprint posted April 11, 2020. doi:10.1101/2020.04.08.20057794
20.
Davis  CE , Hyde  JE , Bangdiwala  SI , Nelson  JJ . An example of dependencies among variables in a conditional logistic regression. In: Modern Statistical Methods in Chronic Disease Epidemiology. John Wiley & Sons; 1986:140-147.
21.
Lin  DY , Wei  LJ .  The Robust inference for the Cox proportional hazards model.   J Am Stat Assoc. 1989;84(408):1074-1078. doi:10.1080/01621459.1989.10478874Google ScholarCrossref
22.
VanderWeele  TJ , Ding  P .  Sensitivity analysis in observational research: introducing the E-value.   Ann Intern Med. 2017;167(4):268-274. doi:10.7326/M16-2607 PubMedGoogle ScholarCrossref
23.
Mahevas  M , Tran V-T, Roumier M, et al. No evidence of clinical efficacy of hydroxychloroquine in patients hospitalized for COVID-19 infection with oxygen requirement: results of a study using routinely collected data to emulate a target trial. medRxiv. Preprint posted April 14, 2020. doi:10.1101/2020.04.10.20060699
24.
Geleris  J , Sun  Y , Platt  J ,  et al.  Observational study of hydroxychloroquine in hospitalized patients with Covid-19.   N Engl J Med. Published online May 7, 2020. doi:10.1056/NEJMoa2012410PubMedGoogle Scholar
25.
Gorgels  APM , Gijsbers  C , de Vreede-Swagemakers  J , Lousberg  A , Wellens  HJJ .  Out-of-hospital cardiac arrest: the relevance of heart failure.   Eur Heart J. 2003;24(13):1204-1209. doi:10.1016/S0195-668X(03)00191-X PubMedGoogle ScholarCrossref
26.
Low  LS , Kern  KB .  Importance of coronary artery disease in sudden cardiac death.   J Am Heart Assoc. 2014;3(5):e001339. doi:10.1161/JAHA.114.001339 PubMedGoogle Scholar
27.
Richardson  S , Hirsch  JS , Narasimhan  M ,  et al; and the Northwell COVID-19 Research Consortium.  Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area.   JAMA. Published online April 22, 2020. doi:10.1001/jama.2020.6775 PubMedGoogle Scholar
28.
Zhou  F , Yu  T , Du  R ,  et al.  Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.   Lancet. 2020;395(10229):1054-1062. doi:10.1016/S0140-6736(20)30566-3 PubMedGoogle ScholarCrossref
29.
Yancy  CW .  COVID-19 and African Americans.   JAMA. Published online April 15, 2020. doi:10.1001/jama.2020.6548 PubMedGoogle Scholar
30.
NIH. COVID-19 treatment guidelines. Accessed April 24, 2020. https://covid19treatmentguidelines.nih.gov/introduction/
31.
Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. Posted April 11, 2020. Accessed April 24, 2020. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/
32.
FDA Drug Safety Communication. FDA cautions against use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems. Posted April 24, 2020. Accessed May 8, 2020. https://www.fda.gov/media/137250/download
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