CORONAVIRUS PANDEMIC UPDATE: STUDY SHOWS CHLOROQUINE AND HYDROXYCHLOROQUINE HAVE NO BENEFIT BUT POTENTIALLY LETHAL
TITLE: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis
AUTHORS: Mandeep R Mehra, Sapan S Desai, Frank Ruschitzka, Amit N Patel
JOURNAL: The Lancet, May 22, 2020
BACKGROUND: Hydroxychloroquine or chloroquine, often in combination with a second-generation macrolide, are being widely used for treatment of COVID-19, despite no conclusive evidence of their benefit. Although generally safe when used for approved indications such as autoimmune disease or malaria, the safety and benefit of these treatment regimens are poorly evaluated in COVID-19.
METHODS: We did a multinational registry analysis of the use of hydroxychloroquine or chloroquine with or without a macrolide (i.e. azithromycin, clarithromycin, erythromycin) for treatment of COVID-19. The registry comprised data from 671 hospitals in six continents. We included patients hospitalised between Dec 20, 2019, and April 14, 2020, with a positive laboratory finding for SARS-CoV-2.
Patients who received one of the treatments of interest within 48 hours of diagnosis were included in one of four treatment groups (chloroquine alone, chloroquine with a macrolide, hydroxychloroquine alone, or hydroxychloroquine with a macrolide), and patients who received none of these treatments formed the control group.
Patients for whom one of the treatments of interest was initiated more than 48 hours after diagnosis or while they were on mechanical ventilation, as well as patients who received remdesivir, were excluded. 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).
FINDINGS: 96,032 patients (mean age 53·8 years, 46·3% women) with COVID-19 were hospitalised during the study period and met the inclusion criteria. Of these, 14 888 patients were in the treatment groups (1868 received chloroquine, 3783 received chloroquine with a macrolide, 3016 received hydroxychloroquine, and 6221 received hydroxychloroquine with a macrolide) and 81 144 patients were in the control group. 10,698 (11·1%) patients died in hospital.
After controlling for multiple confounding factors (age, sex, race or ethnicity, body-mass index, underlying cardiovascular disease and its risk factors, diabetes, underlying lung disease, smoking, immunosuppressed condition, and baseline disease severity), when compared with mortality in the control group (9·3%), hydroxychloroquine (18·0%; hazard ratio 1·335, 95% CI 1·223–1·457), hydroxychloroquine with a macrolide (23·8%; 1·447, 1·368–1·531), chloroquine (16·4%; 1·365, 1·218–1·531), and chloroquine with a macrolide (22·2%; 1·368, 1·273–1·469) were each independently associated with an increased risk of in-hospital mortality.
Compared with the control group (0·3%), hydroxychloroquine (6·1%; 2·369, 1·935–2·900), hydroxychloroquine with a macrolide (8·1%; 5·106, 4·106–5·983), chloroquine (4·3%; 3·561, 2·760–4·596), and chloroquine with a macrolide (6·5%; 4·011, 3·344–4·812) were independently associated with an increased risk of de-novo ventricular arrhythmia during hospitalisation.
INTERPRETATION: Use of a regimen containing hydroxychloroquine or chloroquine (with or without a macrolide) was associated with no evidence of benefit on in-hospital outcomes for COVID-19 (i.e. NO BENEFIT)
But instead, each of these drugs was associated with an increase in the risk of ventricular arrhythmias and a greater hazard for in-hospital death when used for treatment of COVID-19. (i.e. IT’LL KILL YOU)
RECOMMENDATION: These findings suggest that these drug regimens should not be used outside of clinical trials and urgent confirmation from randomised clinical trials is needed.
The Lancet, May 22, 2020: https://www.thelancet.com/lancet/article/s0140673620311806