Verified data from an international registry comprising 671 hospitals in six continents were used to compare patients with COVID-19 who received chloroquine (n=1868), hydroxychloroquine (n=3016), chloroquine with a macrolide (n=3783), or hydroxychloroquine with a macrolide (n=6221) within 48 h of COVID-19 diagnosis, with 81 144 controls who did not receive these drugs. The primary outcome was in-hospital mortality and the occurrence of de-novo non-sustained or sustained ventricular tachycardia or ventricular fibrillation was also analysed.
A Cox proportional hazard model accounting for many confounding variables, including age, sex, ethnicity, comorbidities, other medications, and COVID-19 severity, showed a significant increase in the risk of in-hospital mortality with the four treatment regimens compared with the control group (hazard ratios [HRs] of 1·335 [95% CI 1·2231·457] to 1·447 [1·3681·531]). Analyses using propensity score matching by treatment group supported this result. The increased risk of in-hospital mortality was similar in men (1·293 [1·1781·420] to 1·408 [1·3091·513]) and women (1·338 [1·1691·531] to 1·494 [1·3341·672]). The incidence of repetitive ventricular arrhythmias ranged from 4·3% to 8·1% in patients treated with a 4-aminoquinoline, compared with 0·3% in the control group (p<0·0001).
Despite limitations inherent to the observational nature of this study, Mehra and colleagues should be commended for providing results from a well designed and controlled study of the effects of chloroquine or hydroxychloroquine, with or without a macrolide, in a very large sample of hospitalised patients with COVID-19. Their results indicate an absence of benefit of 4-aminoquinoline-based treatments in this population and suggest that they could even be harmful.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2820%2931174-0/fulltext