An observational study on nearly 100,000 Covid-19 patients spanning 671 hospitals on six continents, by far the largest yet, has raised concerns over hydroxychloroquine or chloroquine as treatment. The study, published on Lancet, was unable to confirm any benefit of the drugs, when used alone or in combination with macrolide, but said: “each of these drug regimens was associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias”.
Disturbances in heart rhythm was a known side effect of hydroxychloroquine, a decades-old drug used against malaria and lupus, and underpinned the decision by the US Centers for Disease Control and Prevention to remove its prescription from its Covid-19 guidelines.
The study involved 96,032 patients (mean age 53.8) hospitalised with Covid-19. Of these, 14,888 were administered with the drugs — 1,868 received chloroquine, 3,783 chloroquine with a macrolide, 3,016 hydroxychloroquine, and 6,221 hydroxychloroquine with a macrolide — while 81,144 patients were in a control group that received no drug.
After controlling for confounding factors such as age, sex, and underlying cardiovascular or lung disease, the study found, as against the mortality rate of 9.3% in the controlled group, those administered with hydroxychloroquine showed a mortality rate of 18%, hydroxychloroquine with a macrolide 23·8%, chloroquine 16·4%, and chloroquine with a macrolide 22·2%. The incidence of de novo (new) ventricular arrhythmias was between 4.3% and 8.1%, as against 0.3% in the controlled group.
“It’s no longer that hydroxychloroquine has no sign of efficacy, it is associated with an increase in mortality,” Eric Topol, director and founder of the Scripps Research Translational Institute, tweeted in response to the study.
Yet, the Indian Council of Medical Research (ICMR), in its new guidelines, has recommended wider use of hydroxychloroquine, recommending it as a prophylactic for all asymptomatic healthcare workers treating Covid-19, including those in quarantine centres. Prophylactic refers to preventive treatment.
ICMR’s recommendations come with some caveats: The drug should be discontinued if it causes side-effects such as cardiomyopathy and rhythm disorders; is not to be given to people known to have retinopathy, hypersensitivity to HCQ or G6PD deficiency (a condition that causes red blood cells to break down; and is not meant for prophylaxis children under 15 years of age and pregnant women.
