Treatment With Hydroxychloroquine or Azithromycin for COVID-19

Quick Takes

  • Hydroxychloroquine with or without azithromycin is not associated with differences in mortality in hospitalized patients with COVID-19.
  • Combination hydroxychloroquine and azithromycin was, however, associated with higher risk of cardiac arrest.
  • Until clinical trials show benefit, hydroxychloroquine and azithromycin should not be prescribed for COVID-19.

Study Questions:

Is the use of hydroxychloroquine with or without azithromycin in patients with coronavirus disease 19 (COVID-19) associated with in-hospital mortality?


In this retrospective, multicenter study, the authors selected a random sample (n = 1,438) of all patients (n = 8,970) admitted for COVID-19 to New York City healthcare centers between March 15 and 28, and examined the association between hydroxychloroquine, azithromycin, and outcomes. Patients were categorized in four groups: 1) hydroxychloroquine with azithromycin (n = 735, 51.1%), 2) hydroxychloroquine without azithromycin (n = 271, 18.8%), 3) azithromycin alone (n = 211, 14.7%), and 4) neither drug (n = 211, 14.7%). The primary outcome was in-hospital mortality. Secondary outcomes included cardiac arrest, arrhythmia, and prolonged QT.


While median age, race, and time of initiation were similar between patients receiving hydroxychloroquine or azithromycin, and those who did not, patients in the treatment groups, particularly hydroxychloroquine + azithromycin, were more likely to have clinically severe disease and be admitted to the intensive care unit. Overall in-hospital mortality was 20.3%. In unadjusted analyses, significant differences in mortality were observed across groups: hydroxychloroquine + azithromycin 25.7%, hydroxychloroquine alone 19.9%, azithromycin alone 10.0%, and neither-drug 12.7%. However, in multivariable analyses, the difference in mortality was no longer significant. Similarly, while there were differences in electrocardiography abnormalities between groups, those were not significant in multivariable analyses. Cardiac arrest, however, was more likely in patients receiving hydroxychloroquine + azithromycin (adjusted odds ratio, 2.13; 95% confidence interval, 1.12-4.05) compared to the remainder of the groups.


The use of hydroxychloroquine, azithromycin, or both were not associated with differences in in-hospital mortality. Cardiac arrest was more likely in patients receiving hydroxychloroquine and azithromycin.


This observational study confirms prior findings of a lack of association between hydroxychloroquine, azithromycin use, and outcomes in patients hospitalized for COVID-19. This study, however, samples 25 facilities across New York City, providing some generalizability. Short of a randomized clinical trial, no findings from observational studies can provide definitive conclusions on the effectiveness of therapy. However, the significant increase in the risk of cardiac arrest with hydroxychloroquine and azithromycin is a major cause for concern and should give pause to any clinician considering these therapies for the treatment of COVID-19.

Clinical Topics: Arrhythmias and Clinical EP, COVID-19 Hub, Prevention, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Novel Agents, Statins

Keywords: Arrhythmias, Cardiac, Azithromycin, Coronavirus, Coronavirus Infections, COVID-19, Electrocardiography, Heart Arrest, Hospital Mortality, Hydroxychloroquine, Intensive Care Units, Primary Prevention, severe acute respiratory syndrome coronavirus 2

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