A new study published in medRxiv on April 21 indicates that treatment with hydroxychloroquine increases overall mortality in patients hospitalized with coronavirus disease 2019 (COVID-19).1
 
Hydroxychloroquine and azithromycin have been widely used in COVID-19 treatments based on anecdotal and limited observational evidence. Despite this lack of evidence, the FDA authorized the emergency use of hydroxychloroquine to treat patients with COVID-19.1
 
In order to assess the results of treating patients with COVID-19 with these drugs, the researchers performed an analysis of data collected from patients hospitalized with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in all Veterans Health Administration medical centers until April 11, 2020. The researchers categorized patients based on their exposure to hydroxychloroquine alone (HC) or with azithromycin (HC+AZ) as treatments in addition to the standard supportive treatment for COVID-19.1
 
The results of the study showed that the 2 primary outcomes of treatment with either HC or HC+AZ were death and the need for mechanical ventilation. The researchers determined the association between treatment and these primary outcomes by using competing risk hazard regression, with adjustments for clinical characteristics via propensity scores. The results also took into account discharge and death as competing risks, and subdistribution hazard ratios were presented.1
 
In the study, a total of 368 patients were evaluated. A total of 97 patients were in the HC group, while 113 were in the HC+AZ group, and 158 were in the no HC group. The rates of death in the HC and HC+AZ groups were 27.8% and 22.1%, respectively, while no HC was at 11.4%. Rates of ventilation in the HC, HC+AZ, and no HC groups were 13.3%, 6.9%, 14.1%, respectively.1
 
When compared with the no HC group, the risk of death from any cause was higher for the HC group, although this was not the result in the HC+AZ group. However, the risk of ventilation was similar in the HC group and in the HC+AZ group compared with the no HC group.1
 
Based on these results, the researchers concluded that the use of hydroxychloroquine, either with or without azithromycin, did not reduce the risk of needing mechanical ventilation for patients hospitalized with COVID-19. Additionally, the results also showed a clear association with increased overall mortality in patients treated with hydroxychloroquine alone.1
 
This echoes the information published in the Canadian Medical Association Journal in early April, which reviewed the potentially harmful effects of chloroquine, hydroxychloroquine, and azithromycin for patients with confirmed SARS-CoV-2 infection.2
 
“Physicians and patients should be aware of several rare but potentially life-threatening adverse effects of chloroquine and hydroxychloroquine,” said David Juurlink, MD, PhD, FRCPC, Division of Clinical Pharmacology and Toxicology, Sunnybrook Health Sciences Centre, and a senior scientist at ICES, in a press release.3
 
The article went on to present a brief synopsis of the potential harms associated with treating patients with COVID-19 with these drugs, which included cardiac arrhythmias, hypoglycemia, neuropsychiatric effects, interactions with other drugs, metabolic variability, and overdose. This summary of potential adverse effects highlighted that the prescription of these medications to patients with COVID-19 should be approached with caution.2
 
In the new study in medRxiv, the data confirmed this cautionary approach to treatment with these drugs, according to the authors. The results of the study demonstrated not only an increased mortality for patients treated with hydroxychloroquine, but a lack of benefit in treating patients with hydroxychloroquine and azithromycin, according to the study authors. With this, the researchers highlighted the importance of basing widespread treatment decisions on the results of ongoing prospective, randomized, controlled studies in the future.1
 
REFERENCES
  1. Magagnoli J, Narendran S, Pereira F, et al. Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19. medRxiv. 2020. doi: 10.1101/2020.04.16.20065920.
  2. Juurlink DN. Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection. Canadian Medical Association Journal. 2020. doi: 10.1503/cmaj.200528.
  3. Potential harms of chloroquine, hydroxychloroquine and azithromycin for treating COVID-19 [news release]. ScienceDaily; April 8, 2020. sciencedaily.com/releases/2020/04/200408125521.htm. Accessed April 9, 2020.