Editor’s Note: The following article was based on published research that has recently been retracted by The Lancet due to concerns over data integrity. The full retraction statement can be found here.
A multinational observational study evaluating the use of hydroxychloroquine or chloroquine, either as monotherapy or with a macrolide, found that these treatments may increase the risk of ventricular arrhythmia and death in patients hospitalized with coronavirus disease 2019 (COVID-19).
The analysis included 96,032 patients with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who were hospitalized between December 20, 2019 and April 1, 2020. The treatment groups included: chloroquine monotherapy (n=1868), chloroquine plus a macrolide (n=3783), hydroxychloroquine monotherapy (n=3016), hydroxychloroquine plus a macrolide (n=6221), and no treatment of interest (control group; n=81,144); the macrolides included in the study were azithromycin or clarithromycin. Patients were excluded if they received treatment more than 48 hours after diagnosis, were on mechanical ventilation, or received remdesivir.
In-hospital mortality and the occurrence of de novo ventricular arrhythmias (nonsustained or sustained ventricular tachycardia or ventricular fibrillation) were designated the main outcomes of interest. “For the primary analysis of in-hospital mortality, we controlled for confounding factors, including demographic variables, comorbidities, disease severity at presentation, and other medication use (cardiac medications and other antiviral therapies),” the study authors explained.
Findings from the analysis showed an increased risk of in-hospital mortality with chloroquine (16.4%; hazard ratio [HR] 1.365; 95% CI, 1.218-1.531), chloroquine plus a macrolide (22.2%; HR 1.368; 95% CI, 1.273-1.469), hydroxychloroquine (18.0%; HR 1.335; 95% CI, 1.223-1.457), and hydroxychloroquine plus a macrolide (23.8%; HR 1.447; 95% CI, 1.368-1.531), compared with control (9.3%). Moreover, the authors noted that higher body mass index (BMI) was linked to worse in-hospital survival.
Additionally, all 4 of the treatments were associated with an increased risk of de novo ventricular arrhythmia: chloroquine (4.3%; HR 3.561; 95% CI, 2.760-4.596), chloroquine plus a macrolide (6.5%; HR 4.011; 95% CI, 3.344-4.812), hydroxychloroquine (6.1%; HR 2.369; 95% CI, 1.935-2.900), and hydroxychloroquine plus a macrolide (8.1%; HR 5.106; 95% CI, 4.106-5.983), compared with control (0.3%).
“Several countries have advocated use of chloroquine and hydroxychloroquine, either alone or in combination, as potential treatments for COVID-19,” said Prof Dr Frank Ruschitzka, Director of the Heart Center at University Hospital Zurich and co-author of the study. “Justification for repurposing these medicines in this way is based on a small number of anecdotal experiences that suggest they may have beneficial effects for people infected with the SARS-CoV-2 virus. However, we now know from our study that the chance that these medications improve outcomes in COVID-19 is quite low.”
Mehra MR, Desai SS, Ruschitzka F, Patel AN. Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis [published online May 22, 2020]. The Lancet. doi: org/10.1016/S0140-6736(20)31180-6.