Hydroxychloroquine: Drug touted by Trump linked to higher death rates in new coronavirus study
Hydroxychloroquine, the anti-malarial drug touted by US President Donald Trump, has been linked to higher rates of death in a study involving US veterans, who were hospitalized with the new coronavirus. The findings raise questions about the safety and efficacy of a treatment that has seen widespread use in the Covid-19 pandemic. Currently, there are no approved drugs for Covid-19.
The research team from the US examined data from patients hospitalized with confirmed Covid-19 in all US Veterans Health Administration medical centers until April 11. Patients were categorized based on their exposure to hydroxychloroquine alone (HC) or with azithromycin (AZ+hydroxychloroquine) as treatments in addition to standard supportive management for Covid-19.
“Despite limited and conflicting data on the use of hydroxychloroquine in patients with Covid-19, the US Food and Drug Administration (FDA) has authorized the emergency use of hydroxychloroquine when clinical trials are unavailable or infeasible. Hydroxychloroquine, alone or in combination with azithromycin, is being widely used in Covid-19 therapy based on anecdotal and limited observational evidence,” says the research team.
“Multiple prospective, randomized trials of hydroxychloroquine are now underway and will, in due course, provide valuable information about safety and efficacy. However, given its increasingly widespread use, not only as therapy but also as prophylaxis for Covid-19, there is a great and immediate need to obtain insights into the clinical outcomes among patients currently treated with hydroxychloroquine, particularly because of the non-negligible toxicities associated with its use,” they add.
Accordingly, a total of 368 patients were evaluated in the study by experts from Columbia VA Health Care System, Columbia; University of South Carolina, Columbia; and University of Virginia School of Medicine, Charlottesville, Virginia. The study comprised only men whose average age was over 65 years. The experts had initially identified 385 patients who were hospitalized with confirmed SARS-CoV-2 infection at Veterans Health Administration medical centers, but because the number of female patients in this cohort (17) were too small, they were omitted from the study.
The analysis shows that there were 27 deaths (27.8%) in the hydroxychloroquine group, 25 deaths (22.1%) in the hydroxychloroquine+azithromycin group, and 18 deaths (11.4%) in the group that did not use hydroxychloroquine. Mechanical ventilation occurred in 13.3% of the hydroxychloroquine group, 6.9% of the hydroxychloroquine+azithromycin group, and 14.1% in the group that did not use hydroxychloroquine.
Based on their analysis, the researchers say that compared to those patients who did not use hydroxychloroquine, there was a higher risk of death among patients who were given the drug, but not in the group who were given a combination of hydroxychloroquine and azithromycin. In this study, the team found no evidence that the use of hydroxychloroquine, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with Covid-19.
These findings highlight the importance of awaiting the results of ongoing prospective, randomized, controlled studies before the widespread adoption of these drugs, recommends the team. The experts recommend using caution in using hydroxychloroquine in hospitalized Covid-19 patients, particularly when not combined with azithromycin.
“This nationwide retrospective study of the largest integrated healthcare system in the US provides the largest dataset yet reported of the outcomes of Covid-19 patients treated with hydroxychloroquine, with or without azithromycin, anywhere in the world,” says the study, a pre-print version of which has been published. “Specifically, hydroxychloroquine use, with or without co-administration of azithromycin, did not improve mortality or reduce the need for mechanical ventilation in hospitalized patients. On the contrary, hydroxychloroquine use alone was associated with an increased risk of mortality compared to standard care alone,” the findings state.
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A panel of experts convened by the National Institute of Allergy and Infectious Diseases had earlier recommended against the use of a combination of hydroxychloroquine and azithromycin for the treatment of Covid-19 patients because of the “potential for toxicities.”
“There are insufficient clinical data to recommend either for or against using chloroquine or hydroxychloroquine for the treatment of Covid-19. If chloroquine or hydroxychloroquine is used, clinicians should monitor the patient for adverse effects,” say the guidelines.
Additionally, in guidelines issued by the Infectious Diseases Society of America (IDSA), citing the knowledge gap, experts said that among patients who have been admitted to the hospital with Covid-19, the panel recommends hydroxychloroquine/chloroquine in the context of a clinical trial. Among patients who have been admitted to the hospital with Covid-19, the IDSA guideline panel recommended hydroxychloroquine/chloroquine plus azithromycin only in the context of a clinical trial.
These recommendations acknowledge the current “knowledge gap” and aim at avoiding premature favorable recommendations for potentially ineffective or harmful interventions, say medical experts.
“The panel agreed that the overall certainty of the evidence was very low due to concerns with risk of bias, inconsistency, indirectness, imprecision, and publication bias. The guideline panel recommends that, because of uncertainty regarding its risks and benefits, the use of hydroxychloroquine should be in the context of a clinical trial. Because of the potential for toxicity, the panel recommends that the hydroxychloroquine plus azithromycin combination only be used in the context of a clinical trial. Additional randomized controlled trials and prospective outcome registries are needed to inform research for treatment with hydroxychloroquine alone or in combination with azithromycin for patients with Covid-19,” says the guidance.