Again, Antimalarial Use Fails to Benefit COVID Save

Today Lancet reported the results of another retrospective trial showing that hydroxychloroquine or chloroquine, alone or with a macrolide antibioitic, offered no additional benefits to COVID-19 patients, but was associated with higher rates of mortality and arrhythmia.

Analysis of a multinational registry with data from 671 hospitals on six continents, looked at those taking either hydroxychloroquine (HCQ) or chloroquine (CQ) with or without a macrolide SARS-CoV-2 positive patients.

To be included therapy had to be started withing 48 hrs. of diagnosis and outcomes from four treatment groups (chloroquine alone, chloroquine with a macrolide, hydroxychloroquine alone, or hydroxychloroquine with a macrolide), and untreated patients were compared. The main outcomes of interest were in-hospital mortality and the occurrence of de-novo ventricular arrhythmias (non-sustained or sustained ventricular tachycardia or ventricular fibrillation).

The study included 96 032 hospitalised COVID patients (mean age 53·8 years, 46·3% women); 14 888 of whom received treatment (1868 CQ, 3783 CQ+M, 3016 HCQ, 6221 HCQ+M) and 81 144 controls.

Eleven percent of patients died in hospital. Mortality rates were:

• Controls 9·3% 
• HCQ 18·0% (hazard ratio 1·335, 95% CI 1·223–1·457)
• HCQ + macrolide  23·8  (HR 1·447, 1·368–1·531)
• CQ 16·4%   (HR 1·365, 1·218–1·531)
• CQ + macrolide  22·2%  (HR 1·368, 1·273–1·469)

Risk of de-novo ventricular arrhythmia were:

• Controls 0·3%
• HCQ 6·1% (HR 2·369, 1·935–2·900)
• HCQ + macrolide 8·1% (HR 5·106, 4·106–5·983)
• CQ  4·3% (HR 3·561, 2·760–4·596)
• CQ + macrolide 6·5%  (HR 4·011, 3·344–4·812)

There was no benefit to antimalarial therapy; and use of these agents was associated with a higher risk of death and arrhythmia. These findings may reflect the need for advanced therapies in sicker patients, rather than a direct toxic effect of HCQ or CQ.