President Donald Trump has been a frequent cheerleader for a combination of the antimalarial hydroxychloroquine and the antibiotic azithromycin as a COVID-19 treatment. He promoted the drugs nearly 50 times, despite pleas from scientists to let studies decide if the treatment worked or not. On Monday, Trump said he was taking hydroxychloroquine to prevent coronavirus infection, although there's no evidence it can do that.
Dr. Mandeep Mehra, medical director of the Brigham and Women's Hospital Heart and Vascular Center and the lead author of the study, told CNN he would recommend hospitals stop using these drugs to treat COVID-19.
"Our data has very convincingly shown that across the world in a real-world population that this drug combination, whichever way you slice it or dice it, does not show any evidence of benefit, and in fact, is immutably showing a signal of grave harm," he said.
For the new study, researchers analyzed data from more than 96,000 patients with confirmed COVID-19 from 671 hospitals on six continents. All were hospitalized from late December to mid-April, and had died or been discharged by April 21. Just under 15,000 patients were treated with hydroxychloroquine or chloroquine, or one of those drugs combined with an antibiotic.
Despite risks, Trump says he's taking hydroxychloroquine to protect against coronavirus
All four of those treatments were linked with a higher risk of dying in the hospital. About one in 11 patients in the control group -- who got none of the drugs -- died in the hospital. About one in six patients treated with chloroquine or hydroxychloroquine alone died in the hospital. About one in five treated with chloroquine and an antibiotic died and almost one in four treated with hydroxychloroquine and an antibiotic died.
Researchers also found that serious heart arrhythmias were more common among patients receiving any of the four treatments. The largest increase was among the group treated with hydroxychloroquine and an antibiotic; 8% of those patients developed a heart arrhythmia, compared with 0.3% of patients in the control group.
Dr. David Boulware, an infectious disease expert with the University of Minnesota who is also studying hydroxychloroquine as a COVID-19 treatment, said the study reinforces that the drug "probably has no benefit and likely has some increased risk of mortality" for coronavirus patients.
"Before, the data suggested there may be no overall benefit of hydroxychloroquine, but this study shows increasing evidence that not only is there no benefit, there may likely be harm," Boulware said. "There is increasing evidence that hydroxychloroquine should not be used in hospitalized patients."
Even as chloroquine shows potential for treating COVID-19, doctors warn caution needed
Smaller studies, including one published in the Journal of the American Medical Association, have shown hydroxychloroquine did not help fight the coronavirus and could cause heart problems. Another study published in The New England Journal of Medicine showed it provided no benefits to COVID-19 patients.
Even before these reports were published, the US Food and Drug Administration issued a warning about using the drugs in coronavirus patients outside of clinical trials, and the National Institutes of Health COVID-19 treatment guidelines warned against using hydroxychloroquine and azithromycin together.
Mehra, the study author, said the latest findings can't necessarily be applied to people who are trying to prevent infection with Covid-19, adding that the researchers would endorse clinical trials for that case.
"But even in those patients, the use of this drug regimen in an off-label capacity should really be shunned and avoided," he said, particularly because of the heart arrhythmia risks. Off-label means for conditions not approved by the FDA. Hydroxychloroquine and chloroquine are approved to treat or prevent malaria. Hydroxychloroquine is also approved to treat autoimmune conditions such as lupus and rheumatoid arthritis.