A study into the use of hydroxychloroquine or chloroquine, published in The Lancet, has failed to find a benefit in hospital-outcomes from the use of the drugs for the treatment of COVID-19. The study also associates the drug with an increased frequency of ventricular arrhythmias in patients.
Authored by Mandeep Mehra (Brigham and Women’s Hospital Heart and Vascular Center and Harvard Medical School, Boston, USA) and colleagues, the study found that the use of the drugs, either alone or with a macrolide, was associated with decreased in-hospital survival.
Hydroxychloroquine is an oral prescription drug that has been used for the treatment of malaria and certain inflammatory conditions, and is under investigation in clinical trials for pre- or post-exposure prophylaxis of SARS-CoV-2 infection, and treatment of patients with mild, moderate, and severe COVID-19. Its use has been linked to torsade de pointes and arrhythmia.
In order to assess the efficacy and safety of the drug as a COVID-19 treatment, Mehra and colleagues a multinational registry analysis of the use of hydroxychloroquine or chloroquine 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 h 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.
A total of 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 (1,868 received chloroquine, 3,783 received chloroquine with a macrolide, 3,016 received hydroxychloroquine, and 6,221 received hydroxychloroquine with a macrolide) and 81,144 patients were in the control group. A total of 10,698 (11·1%) patients died in hospital.
Furthermore, the study team found that 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.
Additionally, 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.