Hydroxychloroquine, chloroquine tied to higher risk of death when used to treat COVID-19

A registry analysis published Friday in The Lancet that included nearly 15,000 people treated with hydroxychloroquine or chloroquine, either alone or together with a macrolide, was unable to confirm any benefit of the malaria drugs for COVID-19. Furthermore, the study found that these drug regimens were associated with decreased in-hospital survival and a higher frequency of ventricular arrhythmias.

The registry comprised data from 671 hospitals in several countries, and included patients hospitalised between December 20, 2019, and April 14, 2020, who were positive for SARS-CoV-2. Patients, treated within 48 hours of diagnosis, received either chloroquine, alone or with a macrolide, or hydroxychloroquine, also alone or with a macrolide, while patients who received none of these treatments formed the control group. Excluded from the analysis were patients who were treated with any of these regimens more than 48 hours after diagnosis or while they were on mechanical ventilation, as well as those who were given Gilead Sciences' remdesivir. Researchers assessed in-hospital mortality and the occurrence of de-novo ventricular arrhythmias.

The authors noted that 14 888 patients fell into one of the four treatment groups, while 81 144 patients were in the control arm. In total, 10 698 patients died in hospital. They reported that after controlling for various factors, the mortality rate for patients given chloroquine alone was 16·4%, while for those treated with chloroquine plus a macrolide, the rate was 22·2%. The mortality rates for hydroxychloroquine, given alone or with a macrolide, were 18% and 23·8%, respectively, while the incidence in the control group was 9·3%.

Similarly, compared with an incidence of 0·3% among controls, the respective rates of de-novo ventricular arrhythmia during hospitalisation were 4·3% and 6·5% for chloroquine, alone or with a macrolide, while for the hydroxychloroquine treatment groups, the rates were 6·1% and 8·1%, respectively.

'Should not be used outside of trials'

The authors said the study had several limitations, and cautioned that a cause-and-effect relationship between drug therapy and survival should not be inferred. Nevertheless, they concluded that the "findings suggest that these drug regimens should not be used outside of clinical trials and urgent confirmation from randomised clinical trials is needed." The latest news come in the wake of disappointing results from a pair of studies published in the BMJ indicating that hydroxychloroquine did not significantly help patients with COVID-19.

Earlier this month, the US National Institutes of Health said it was launching a Phase IIb clinical trial evaluating the combination of hydroxychloroquine plus azithromycin to treat patients with mild-to-moderate COVID-19 in the US.

The FDA recently issued an emergency-use authorisation for hydroxychloroquine and chloroquine for treating hospitalised adults and adolescents with COVID-19, when a clinical trial is not available or feasible. However, the agency has since warned about the need to closely monitor patients, as known side effects of the antimalarial drugs, such as potentially life-threatening heart rhythm problems, have been reported when prescribed to treat or prevent COVID-19.

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