A study of 96,000 hospitalized coronavirus patients on six continents found that those who received an antimalarial drug promoted by President Trump as a ‘‘game changer’’ in the fight against the virus had a significantly higher risk of death compared with those who did not.
People treated with hydroxychloroquine, or the closely related drug chloroquine, were also more likely to develop a type of irregular heart rhythm, or arrhythmia, that can lead to sudden cardiac death, it concluded.
The study, obtained early by The Washington Post and published Friday in the medical journal the Lancet, is the largest analysis to date of the risks and benefits of treating COVID-19 patients with antimalarial drugs. It is based on a retrospective analysis of medical records, not a controlled study in which patients are divided randomly into treatment groups — a method considered the gold standard of medicine. But the sheer size of the study was convincing to some scientists.
‘‘It’s one thing not to have benefit, but this shows distinct harm,’’ said Eric Topol, a cardiologist and director of the Scripps Research Translational Institute.
David Maron, director of preventive cardiology at Stanford’s School of Medicine, said that ‘‘these findings provide absolutely no reason for optimism that these drugs might be useful in the prevention or treatment of COVID-19.’’
Past studies also found scant or no evidence of hydroxychloroquine’s benefit in treating sick patients, while reports mounted of dangerous heart problems associated with its use. As a result, the Food and Drug Administration last month warned against the use of the drug outside hospital settings or clinical trials.
The new analysis — by Mandeep Mehra, a Harvard Medical School professor and physician at Brigham and Women’s Hospital, and colleagues at other institutions — included patients with a positive laboratory test for COVID-19 who were hospitalized between Dec. 20, 2019, and April 14, 2020, at 671 medical centers worldwide. The mean age was 54 years, and 53 percent were men. Those who were on mechanical ventilators or who received remdesivir, an antiviral drug made by Gilead Sciences that has shown promise in decreasing recovery times, were excluded.
Nearly 15,000 of the 96,000 patients in the analysis were treated with hydroxychloroquine or chloroquine alone or in combination with an antibiotic known as a macrolide, such as azithromycin, within 48 hours of their diagnosis.
The difference between patients who received the antimalarials and those who did not was striking.
For those given hydroxychloroquine, there was a 34 percent increase in risk of mortality and a 137 percent increased risk of serious heart arrhythmias. For those receiving hydroxychloroquine and an antibiotic — the cocktail endorsed by Trump — there was a 45 percent increased risk of death and a 411 percent increased risk of serious heart arrhythmias.
Those given chloroquine had a 37 percent increased risk of death and a 256 percent increased risk of serious heart arrhythmias. For those taking chloroquine and an antibiotic, there was a 37 percent increased risk of death and a 301 percent increased risk of serious heart arrhythmias.
Cardiologist Steven Nissen of the Cleveland Clinic said the new data, combined with data from smaller previous studies, suggests that the drug ‘‘is maybe harmful and that no one should be taking it outside of a clinical trial.’’
Jesse Goodman, a former FDA chief scientist who is now a Georgetown University professor, called the report ‘‘very concerning.’’ He noted, however, that it is an observational study, rather than a randomized controlled trial, so it shows correlation between the drugs and certain outcomes, rather than a clear cause and effect.
Peter Lurie, a former top FDA official who now heads the Center for Science in the Public Interest, called the report ‘‘another nail in the coffin for hydroxychloroquine — this time from the largest study ever.’’
He said it was time to revoke the emergency use authorization issued by the FDA, which approved the drug for seriously ill patients who were hospitalized or for whom a clinical trial was not available.
The new study’s findings cannot necessarily be extrapolated to people with mild illness at home or those, like Trump, who are taking the antimalarials as a prophylactic. The president stunned many doctors earlier this week when he said he was taking a pill ‘‘every day’’ — despite FDA warnings that the use of the drug should be limited to those in a hospital setting or in clinical trials. (He has since said he is close to finishing his course of treatment and would stop taking the medication in ‘‘a day or two.”)
A large study of health-care workers that examines the use of hydroxychloroquine as a preventive measure against COVID-19 is in the works, but no results have been released.
There have been at least 13 studies in recent months on hydroxychloroquine or chloroquine as a treatment for COVID-19 patients. They have included randomized controlled studies and observational analyses encompassing patients on the continuum from mild illness to those near death. Evidence of any benefit has been almost nonexistent. But many found an increased risk in adverse cardiac reactions — especially when combined with the antibiotic azithromycin.