Hydroxychloroquine and COVID-19: No survival benefit, potential arrhythmia link
medwireNews: An increasing number of studies provide evidence against the use of hydroxychloroquine for the treatment of COVID-19, with some results even suggesting it could be harmful; this report rounds up some of the most recent research and recommendations on hydroxychloroquine and COVID-19.
No evidence of a protective effect on mortality risk
Two observational studies from New York, USA, suggest no impact of hydroxychloroquine use on mortality risk among hospitalized patients with COVID-19.
In the first, published in The New England Journal of Medicine, Neil Schluger (Columbia University Irving Medical Center) and colleagues analyzed the outcomes of 1376 patients, of whom 58.9% were treated with hydroxychloroquine (600 mg twice daily on day 1 and 400 mg/day thereafter for a median of 5 days). In all, 32.3% of hydroxychloroquine-treated patients and 14.9% of those in the control group experienced the primary endpoint of intubation or death, and there was no significant difference in risk for this endpoint in a propensity score-matched analysis.
The second study evaluated hospitalized COVID-19 patients treated with either hydroxychloroquine plus azithromycin (n=735), hydroxychloroquine alone (n=271), azithromycin alone (n=211), or neither drug (n=221). Overall in-hospital mortality rates in the four groups were 25.7%, 19.9%, 10.0%, and 12.7%, respectively, with no significant between-group differences after adjustment for potential confounders. Eli Rosenberg (University at Albany School of Public Health) and co-authors conclude in JAMA that hydroxychloroquine use was not associated with a reduction in mortality-risk, but caution that “the interpretation of these findings may be limited by the observational design.”
The results of the two US studies are supported by an open-label randomized trial conducted at 16 centers in China. Qing Xie (Shanghai Jiao Tong University School of Medicine) and co-investigators report in The BMJ that the probability of negative conversion – defined as two negative SARS-CoV-2 test reports at least 24 hours apart without a subsequent positive test result – was comparable among 75 hospitalized COVID-19 patients treated with hydroxychloroquine plus standard of care and 75 given standard care only, at 85.4% and 81.3%. Hydroxychloroquine was given at a loading dose of 1200 mg/day for 3 days and 800 mg/day thereafter, while standard care was given according to Chinese guidelines for the management of COVID-19.
Findings from an observational study carried out in France also support a lack of benefit of hydroxychloroquine for people with COVID-19. Among hospitalized patients who required oxygen but not intensive care, rates of survival without transfer to the intensive care unit over 21 days were not significantly different among the 84 patients who received hydroxychloroquine and the 89 who did not (76 vs 75%). Matthieu Mahévas (Paris-Est Créteil University) and co-researchers note in The BMJ that rates of overall survival and survival without acute respiratory distress were comparable among the two groups.
Potential harms of hydroxychloroquine
In addition to the research demonstrating a lack of association between hydroxychloroquine use and improved outcomes for COVID-19 patients, findings from two studies suggest that those treated with the agent may be at increased risk for heart rhythm alterations.
Nicholas Mercuro (Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA) found that among 37 hospitalized COVID-19 patients treated with hydroxychloroquine, seven developed a prolonged QTc interval of 500 milliseconds or more, while three had a change of 60 milliseconds or more. And a corresponding 11 and seven of 53 patients treated with hydroxychloroquine plus azithromycin experienced these adverse events (AEs). The researchers also note in JAMA Cardiology that 10 patients discontinued hydroxychloroquine early due to QTc interval prolongation; other AEs included hypoglycemia and intractable nausea, and one patient treated with both drugs experienced torsades de pointes, which they say “has yet to be reported elsewhere in the literature.”
A second study, also published in JAMA Cardiology, investigated QTc intervals in 40 COVID-19 patients admitted to a French intensive care unit. Martin Cour (Hôpital Edouard Herriot, Lyon) and team found that six of 18 patients treated with hydroxychloroquine plus azithromycin experienced an increase in QTc interval of at least 500 milliseconds, as did one of 22 patients given hydroxychloroquine alone, which they say “raises safety concerns about the use of hydroxychloroquine with or without azithromycin for patients with COVID-19, particularly when both drugs are administered together.”
New ACP recommendations
Taking the current evidence into account, the American College of Physicians has issued Practice Points recommending against the use of chloroquine or hydroxychloroquine alone or in combination with azithromycin for the treatment or prevention of COVID-19.
The Practice Points, published in the Annals of Internal Medicine, recommend that the agents should not be used for COVID-19 outside of clinical trials “due to known harms and no available evidence of benefits” in both the general population and in patients with COVID-19. Amir Qaseem (American College of Physicians, Philadelphia, Pennsylvania, USA) and co-authors say that the Practice Points are based on the best available evidence and will be maintained as “a living guidance document, updated as new evidence becomes available.”
medwireNews is an independent medical news service provided by Springer Healthcare. © 2020 Springer Healthcare part of the Springer Nature Group
18 May 2020: The coronavirus pandemic is affecting all healthcare professionals across the globe. Medicine Matters’ focus, in this difficult time, is the dissemination of the latest data to support you in your research and clinical practice, based on the scientific literature. We will update the information we provide on the site, as the data are published. However, please refer to your own professional and governmental guidelines for the latest guidance in your own country.
N Engl J Med 2020; doi:10.1056/NEJMoa2012410
JAMA 2020; doi:10.1001/jama.2020.8630
BMJ 2020; 369: m1849
BMJ 2020; 369: m1844
JAMA Cardiol 2020; doi:10.1001/jamacardio.2020.1834
JAMA Cardiol 2020; doi:10.1001/jamacardio.2020.1787
Ann Intern Med 2020 doi:10.7326/M20-1998