According to a large-scale retrospective analysis published in the International Journal of Infectious Diseases, hydroxychloroquine was associated with a significant decrease in death rate in patients hospitalized with COVID-19, and without heart-related side-effects. Marcus Zervos, division head of infectious disease at the Henry Ford Health System who co-authored the study, said “we attribute our findings that differ from other studies to early treatment, and part of a combination of interventions that were done in supportive care of patients, including careful cardiac monitoring. Our dosing also differed from other studies not showing a benefit of the drug.”
The news follows a number of studies that have recently discontinued hydroxychloroquine testing. In June, the US National Institutes of Health (NIH) stopped a clinical trial of hydroxychloroquine in hospitalised patients with COVID-19 after it was determined that the drug was “very unlikely to be beneficial” in this population. The hydroxychloroquine arms of the World Health Organization’s ongoing global Solidarity Trial and the University of Oxford’s RECOVERY trial have also been halted, as has a Phase III study run by Novartis.
Meanwhile, the FDA also recently revoked emergency use of chloroquine and hydroxychloroquine, saying the drugs “may not be effective to treat COVID-19.”
The latest analysis looked at adults with laboratory-confirmed COVID-19 admitted to the Henry Ford Health System from March 10 to May 2, 2020. The primary objective was to assess treatment with hydroxychloroquine versus hydroxychloroquine plus the antibiotic azithromycin, azithromycin alone, and other treatments for COVID-19. The study involved 2541 patients, with a median age of 64 years, ranging from 53 to 76. Slightly over half were male, and 56% were African American. The median time to follow-up was 28.5 days.
Drug given soon after admission
The authors noted that the vast majority of patients received hydroxychloroquine soon after admission, with 82% given the drug within 24 hours of admission, and 91% within 48 hours. Researchers noted that none of the patients had documented serious heart abnormalities, but they were monitored for a heart condition routinely cited as a reason to avoid the drug as a treatment for COVID-19. The combination of hydroxychloroquine plus azithromycin was reserved for select patients with severe COVID-19 and minimal cardiac risk factors.
Results showed that overall in-hospital mortality was 18.1%. By treatment, 13.5% of those given hydroxychloroquine alone died, compared with 20.1% for hydroxychloroquine plus azithromycin, 22.4% for azithromycin alone and 26.4% for those not treated with either drug. The primary cause of death was respiratory failure, which occurred in 88% of cases, while no patient had documented torsades de pointes. Compared to the group receiving neither hydroxychloroquine nor azithromycin, the authors said hydroxychloroquine provided a 66% decrease in mortality hazard ratio, while hydroxychloroquine plus azithromycin reduced the hazard ratio by 71%.
Early treatment, careful cardiac monitoring
“For hydroxychloroquine to have a benefit, it needs to begin before the patients begin to suffer some of the severe immune reactions that patients can have with COVID-19,” Zervos remarked. The study investigators also monitored patients carefully for heart problems, he said. “Findings of this observational study provide crucial data on experience with hydroxychloroquine therapy, providing necessary interim guidance for COVID-19 therapeutic practice,” the authors concluded.
However, in an accompanying commentary, Todd Lee and colleagues suggested that “as the Henry Ford Health System became more experienced in treating patients with COVID-19, survival may have improved, regardless of the use of specific therapies.” They also noted that “concomitant steroid use in patients receiving hydroxychloroquine was more than double the non-treated group. This is relevant considering the recent RECOVERY trial that showed a mortality benefit with dexamethasone.”