The antimalarial drug being taken by US president Donald Trump has been linked to increased rates of death and heart problems in Covid-19 patients, according to a study published in the medical journal The Lancet.
The study’s authors recommended that hydroxychloroquine, and the closely related drug chloroquine, should not be used to treat patients outside of clinical trials, as they found it did not benefit people suffering from Covid-19 and may have serious side-effects.
Mr Trump has hailed hydroxychloroquine as a “game-changer” for Covid-19 patients and played down the risks because the drug is already used to treat malaria, lupus and arthritis. In early April, he praised the drug and asked: “What have you got to lose?” This week, he said he was taking it as a preventive measure against the disease.
Mandeep Mehra, lead author of the study and executive director of the Brigham and Women’s Hospital Center for Advanced Heart Disease, said randomised clinical trials would be essential to confirm the harm or benefits of the treatments.
“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. Instead, our findings suggest it may be associated with an increased risk of serious heart problems and increased risk of death,” he said.
The US Food and Drug Administration warned late last month that there were reports of serious heart rhythm problems in patients taking the drug and advised doctors not to prescribe it outside of a hospital.
The new study analysed data from almost 15,000 Covid-19 patients receiving a combination of four drug regimens and compared it with a control group of 81,000.
At the end of the study, a higher proportion of people had died in the groups on treatment than among those who were not on the drugs. About one in six patients on hydroxychloroquine or chloroquine alone had died. When taken with an antibiotic, death rates rose to one in four for hydroxychloroquine and one in five for chloroquine. This compared with a death rate in the control group of one in 11.
The researchers cautioned that some of the difference in the rates of mortality was due to underlying differences between patients who received the treatments and those who did not because this was not a randomised clinical trial.
But even after accounting for differences in age, race and pre-existing conditions such as heart disease and diabetes, they found the drugs were associated with an increased risk of death. Patients taking hydroxychloroquine with the antibiotic saw a fivefold increase in the risk of developing a serious heart arrhythmia, even accounting for underlying health conditions and demographic differences.
The trial enrolled some patients in the US, where the drug has an emergency authorisation for use against Covid-19.
“When you look at the recommendations given by regulatory authorities all over the world, what else did they have at the time?” said Frank Ruschitzka, head of cardiology at University Hospital Zurich and a co-author on the study. “In light of this new data, I hope they will rethink some of these recommendations. We can’t rely on anecdotal evidence, whoever it’s coming from. Please rely on the science. Let the data speak.”
Christian Funck-Brentano, a professor at the Sorbonne University, who was not involved in the study, wrote a comment article about it for The Lancet.
He said: “This well-conducted observational study adds to preliminary reports suggesting that chloroquine, hydroxychloroquine, alone or with [the antibiotic] azithromycin, is not useful and may be harmful in hospitalised Covid-19 patients.”