The study, published Friday in the medical journal The Lancet, is the largest analysis to date of the risks and benefits of treating mosquito-19 patients with antimalarial drugs. It is based on a retrospective analysis of medical records, not on a controlled study in which patients are randomly divided into treatment groups, a method considered the gold standard of medicine. But the large size of the study was convincing to some scientists.
“It’s one thing not to take advantage, but it shows clear harm,”
David Maron, director of preventive cardiology at Stanford University School of Medicine, said that “these findings give absolutely no reason to be optimistic that these drugs may be useful in the prevention or treatment of covid-19.”
Past studies have also found little or no evidence of the benefit of hydroxychloroquine in the treatment of sick patients, while reports of dangerous heart problems associated with its use. As a result, the Food and Drug Administration last month warned against using the drug outside of hospital conditions or clinical trials.
The new analysis – by Mandip Mehra, a Harvard lecturer and doctor at Brigham and Women’s Hospital, and colleagues from other institutions – includes patients with a positive laboratory test for covid-19 who were hospitalized between December 20, 2019 and April 14, 2020, in 671 medical centers around the world. The average age was 54, and 53 percent were men. Those who were on mechanical ventilators or receiving remdezivir, an antiviral drug manufactured by Gilead Sciences that showed a promising reduction in recovery time, were excluded.
Nearly 15,000 of the 96,000 patients in the analysis were treated with hydroxychloroquine or chloroquine alone or in combination with a type of antibiotic known as a macrolide, such as azithromycin, within 48 hours of diagnosis.
The difference between patients who have taken antimalarials and those who have not is striking.
For those receiving hydroxychloroquine, there is a 34% increased risk of mortality and a 137% increased risk of serious cardiac arrhythmias. For those receiving hydroxychloroquine and an antibiotic – the Trump-approved cocktail – there was a 45 percent increased risk of death and a 411 percent increased risk of serious cardiac arrhythmias.
Those given chloroquine had a 37 percent increased risk of death and a 256 percent increased risk of serious cardiac arrhythmias. For those taking chloroquine and an antibiotic, there is a 37 percent increased risk of death and a 301 percent increased risk of serious cardiac arrhythmias.
Cleveland Clinic cardiologist Stephen Nissen said the new data, combined with data from smaller previous studies, suggested that the drug “may be harmful and no one should take it outside of a clinical trial.”
Jesse Goodman, a former FDA chief scientist who is now a professor at Georgetown University, called the report “very concerned.” However, he noted that this was an observational study, not a randomized controlled trial, so it showed a correlation between drugs and certain results, rather than a clear cause and effect.
Peter Lurie, a former senior FDA official who now heads the Center for Public Interest Science, called the report “another nail in the hydroxychloroquine coffin – this time from the largest study to date.”
He said it was time to revoke the FDA’s emergency authorization, which approves the drug for seriously ill patients who are hospitalized or for whom there is no clinical trial.
The findings of the new study cannot necessarily be extrapolated to people with minor illnesses at home or such as Trump, who take antimalarials as a prophylactic. The president stunned many doctors earlier this week when he said he was taking the pill “every day” – despite FDA warnings that drug use should be limited to those in hospital or clinical trials. (He has since said he is nearing the end of his treatment and will stop taking the medication after “a day or two.”)
A large study of health professionals examining the use of hydroxychloroquine as a preventative measure against covid-19 is ongoing, but no results have been published.
Taken together, HYDROXYCHLOROQUINE & AZITHROMYCIN have a real chance of being one of the biggest game changers in the history of medicine. FDA has moved mountains – Thanks! Hopefully they will HAVE (H works better with A, International Journal of Antimicrobial Agents) …..
– Donald J. Trump (@realDonaldTrump) March 21, 2020
There have been at least 13 studies in recent months of hydroxychloroquine or chloroquine as a treatment for patients with covid-19. They included randomized controlled trials and observational analyzes involving patients on the continuum from mild illness to people close to death. There is almost no evidence of any benefit, such as viral clearance or improved symptoms. But many have found an increased risk of adverse heart reactions – especially in combination with the antibiotic azithromycin.
Earlier this month, some proponents of hydroxychloroquine were seized in a study by the Langon Health Center at New York University that threw zinc into a mixture of hydroxychloroquine and azithromycin, and showed that the treated group had a higher survival rate. But researchers emphasize that this only shows that the combination has some promise. They said the results could be due to other factors, such as zinc, which was added to the patient’s regimens later in the pandemic when hospital treatments and procedures were improved.
Last week, the National Institutes of Health announced a clinical trial of 2,000 adults to determine whether hydroxychloroquine and azithromycin could be used to treat patients with coronavirus.
Topol, of the Scripps Translation Research Institute, suggested that researchers reconsider the ethics of these tests, given growing evidence of potential harm. “It’s very difficult to ignore this signal and it’s disturbing to keep giving it,” he said.
Jeffrey Barnes, a cardiovascular specialist at the University of Michigan, said the study’s approach and findings were “astounding” to make the “risk of these drugs real.” However, he said that because of the enthusiasm some Americans have for the drug and the results of the Lance study, randomized trials are even more important.
“There has been so much discussion about this drug that I think the scientific and medical community has an obligation to determine the potential benefit or risk in the best possible way,” Barnes said.
When the first hospital began showing up in hospitals in March, doctors had very little to offer. As a result, many gambled on hydroxychloroquine. The drug has been shown to have strong antiviral properties in cell cultures, is widely available and is considered to be quite benign in terms of side effects. For years, hydroxychloroquine has been considered the safest and most effective treatment for malaria, lupus, and rheumatoid arthritis.
But these safety findings are at lower doses than are used in hospitals during the first days of the jump in patients in the United States and especially in healthy patients. It turned out that the population infected with covid-19 in hospitals is already at higher risk of cardiovascular complications because many suffer from high blood pressure or other heart problems. Doctors also found that, to their surprise, the new coronavirus appeared to directly or indirectly attack the heart, including by reducing its ability to pump, creating an imbalance in its electrical rhythms and attacking blood vessels.
Peter Whoriskey contributed to this report.