'Premature, avoidable deaths' renew plea to halt prescribing hydroxychloroquine for COVID-19
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Updated evidence “strongly supports” ending the use of hydroxychloroquine for either preventing or treating COVID-19, due to a lack of benefits combined with potentially fatal cardiovascular complications, according to a meta-analysis.
“In 2021 in the United States alone, there have been more than 560,000 prescriptions of hydroxychloroquine for the prevention, post-exposure and treatment of COVID-19,” Charles H. Hennekens, MD, DrPH, of the Florida Atlantic University Schmidt College of Medicine, in Boca Raton, told Healio Rheumatology.
“Since the onset in February 2020, the United States has been the epicenter of the pandemic and remains the world leader in cases and deaths,” he added. “Last year, the 890,000 prescriptions for hydroxychloroquine were nine-fold greater than the previous year’s, leading to major shortages for the approved indications of autoimmune disease predominantly in younger women.”
Writing in The American Journal of Medicine, Hennekens and colleagues stated, “When the totality of evidence is incomplete, it is appropriate for health care providers to remain uncertain.”
“Nonetheless, regulatory authorities are sometimes compelled to act on incomplete evidence,” they wrote. “On March 28, 2020, the US Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for hydroxychloroquine in COVID-19. By April 24, 2020, the FDA issued a Drug Safety Communication warning about potentially fatal prolongations of the QTc interval detectable on 12-lead electrocardiograms and risks of other serious cardiac arrhythmias.”
To provide an updated perspective on the benefits and risks of hydroxychloroquine in COVID-19, Hennekens and colleagues reviewed the recent major publications of randomized, double-blind, placebo-controlled trials examining the drug in post-exposure prophylaxis and hospitalized patients, with the endpoint of SARS-CoV-2 infections, and their meta-analyses.
In all, the authors reviewed three trials of hydroxychloroquine in post-exposure prophylaxis and two examining the drug in patients who were hospitalized, ultimately conducting their own meta-analysis of the evidence.
In their meta-analysis of hydroxychloroquine in post-exposure prophylaxis, Hennekens and colleagues found a nonsignificant relative risk of 0.9 and a statistically nonsignificant 10% estimated reduction in COVID-19 infection in those treated with the drug. Meanwhile, their meta-analysis of hydroxychloroquine in hospitalized patients with COVID-19 found a nonsignificant relative risk of 1.1 (95% CI 0.99-1.23), as well as a statistically nonsignificant estimated 10% increase in mortality, but with sufficient precision to rule out as small as a 1% reduction.
In addition, although the data suggest equality, the point estimate is in the direction of small harm on mortality, the authors wrote.
According to Hennekens and colleagues, the previous, reassuring safety profile of hydroxychloroquine applied solely to patients with lupus and rheumatoid arthritis, both of which are of greater prevalence in younger and middle-aged women. In these populations, the risks for fatal heart outcomes due to hydroxychloroquine are “reassuringly very low,” read a press release issued by Florida Atlantic University.
In contrast, the risks associated with hydroxychloroquine in patients with COVID-19 are significantly higher, related to fatal cardiovascular complications, as these conditions are much more prevalent in older patients and those with existing heart disease or its risk factors, both of which are more predominant in men, the press release said.
“The recent major randomized, double-blind, placebo-controlled trials of hydroxychloroquine in post-exposure prophylaxis as well as patients hospitalized with COVID-19 provides even stronger support for the halt on prescribing hydroxychloroquine,” Hennekens said. “In addition to a lack of significant benefit, the new randomized evidence shows some suggestion of harm.”
“The prior reassuring safety profile of hydroxychloroquine is applicable to patients with lupus and rheumatoid arthritis, both of which are of greater prevalence in younger and middle-aged women, whose risks of fatal heart outcomes due to hydroxychloroquine are reassuringly very low,” he added. “In contrast, the risks of hydroxychloroquine for patients with COVID-19 are significantly higher because fatal cardiovascular complications due to these drugs are so much higher in older patients and those with existing heart disease or its risk factors, both of which are more predominant in men.”
Hennekens later warned that the continued use of hydroxychloroquine, at the expense of established health measures, will result in continued avoidable death.
“Premature and avoidable deaths will continue to occur if subjects take hydroxychloroquine and avoid the public health strategies of proven benefit,” he said. “These include vaccinations and masking, social distancing, crowd avoidance, and frequent hand and face washing.”
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Hennekens CH, et al. Am J Med. 2021;doi:10.1016/j.amjmed.2021.07.035.
Florida Atlantic University press release.
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