Hydroxychloroquine: Trump’s Covid-19 ‘cure’ increases deaths, global study finds

Hydroxychloroquine, the anti-malarial drug Donald Trump is taking to prevent Covid-19, has increased deaths in patients treated with it in hospitals around the world, a study has shown.

A major study of the way hydroxychloroquine and its older version, chloroquine, have been used on six continents – without clinical trials – reveals a sobering picture. Scientists said the results meant the drug should no longer be given to Covid-19 patients except in proper research settings.

While the paper, published online in the Lancet medical journal, is not a trial designed to assess the drug, it shows that the rush to use it around the world may be ill-advised. Significant numbers of doctors have been prescribing it without evidence. It is known that the drug can cause heart irregularities, but many have claimed it is safe because of its long use treating malaria.

There was a rush to use the drug in Covid-19 cases after the French doctor Didier Raoult said he was curing his patients at La Timone hospital, in Marseille. The US president then claimed hydroxychloroquine – less toxic than the original chloroquine – was a cure, and later said he was taking it himself against coronavirus.

The drugs are fairly safe for patients being treated for malaria, but Covid-19 is a very different disease. The authors of the paper pulled together results for more than 96,000 patients in 671 hospitals, taking one of the drugs, with or without an antibiotic such as azithromycin, between 20 December and 14 April.

The death rate among all groups taking the drugs was higher than among people who were not given them. One in six of those taking one of the drugs died, while one in five died if they were taking chloroquine with an antibiotic, and one in four if they were on hydroxychloroquine and an antibiotic. The death rate among patients not taking the drugs was one in 11.

The statistics are not exactly comparable because, as this was not a trial, there were differences in the age, gender, general health and stage of illness of the patients. But the US authors of the study say, allowing for these differences, there was still higher mortality among those taking the drugs.

The team also found that serious cardiac arrhythmias, which cause the lower chamber of the heart to beat rapidly and irregularly, were more common in all the groups receiving one of the four treatment regimens. The biggest increase was in the group treated with hydroxychloroquine in combination with an antibiotic, where 8% of patients developed a heart arrhythmia compared with 0.3% of patients not given the drugs.

“This is the first large-scale study to find statistically robust evidence that treatment with chloroquine or hydroxychloroquine does not benefit patients with Covid-19,” said Prof Mandeep R Mehra, lead author of the study and executive director of the Brigham and Women’s hospital advanced heart disease center in Boston, US.

“Instead, our findings suggest it may be associated with an increased risk of serious heart problems and increased risk of death. Randomised clinical trials are essential to confirm any harms or benefits associated with these agents. In the meantime, we suggest these drugs should not be used as treatments for Covid-19 outside of clinical trials.”

Others scientists suggested the drugs should no longer be used in Covid-19 treatments, except for carefully controlled clinical trials.

Dr Stephen Griffin, associate professor in the school of medicine, University of Leeds, said the paper was “potentially a landmark study for Covid-19 therapy. While not a placebo-controlled trial, an observational study on this scale undertaken with stringent and meticulous analysis is powerful indeed,” he said.

“Whilst controlled trials will be required for confident affirmation, the indications are that these drugs certainly ought not to be used outside of a trial setting where patients can be monitored for complications. One might also question whether the resources necessary for large studies might be better diverted to other causes, at the same time allowing the drugs themselves to be used for their original purpose.

“Furthermore, it is clear that high-profile endorsements of taking these drugs without clinical oversight are both misguided and irresponsible.”

Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, said it was unlikely that trials would now find any substantial benefit from the drugs. “A definitive answer still awaits the results of the randomised trials, but it is clear that the drugs should not be given for treatment of Covid-19 other than in the context of a randomised trial.

“It might even be said that to go on giving them, other than in a trial, is unethical, given this evidence that is not yet contradicted by other available evidence.”