Hydroxychloroquine in Hospitalized Patients with COVID‐19: Real‐World Experience Assessing Mortality
Frank H Annie, Cristian Sirbu, Keely R Frazier, Mike Broce, B Daniel Lucas
Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, doi:10.1002/phar.2467
INTRODUCTION Hydroxychloroquine (HCQ) for coronavirus disease 2019 (COVID-19) is presently being used off-label or within a clinical trial. OBJECTIVES We investigated a multinational database of patients with COVID-19 with real-world data containing outcomes and their relationship to HCQ use. The primary outcome was all-cause mortality within 30 days of follow-up. METHODS This was a retrospective cohort study of patients receiving HCQ within 48 hours of hospital admission. Medications, preexisting conditions, clinical measures on admission, and outcomes were recorded. RESULTS Among patients with a diagnosis of COVID-19 in our propensity-matched cohort, the mean ages AE SD were 62.3 AE 15.9 years (53.7% male) and 61.9 AE 16.0 years (53.0% male) in the HCQ and no-HCQ groups, respectively. There was no difference in overall 30-day mortality between the HCQ and no-HCQ groups (HCQ 13.1%, n=367; no HCQ 13.6%, n=367; odds ratio 0.95, 95% confidence interval 0.62-1.46) after propensity matching. Although statistically insignificant, the HCQazithromycin (AZ) group had an overall mortality rate of 14.6% (n=199) compared with propensitymatched no-HCQ-AZ cohort's rate of 12.1% (n=199, OR 1.24, 95% CI 0.70-2.22). Importantly, however, there was no trend in this cohort's overall mortality/arrhythmogenesis outcome (HCQ-AZ 17.1%, no HCQ-no AZ 17.1%; OR 1.0, 95% CI 0.6-1.7). CONCLUSIONS We report from a large retrospective multinational database analysis of COVID-19 outcomes with HCQ and overall mortality in hospitalized patients. There was no statistically significant increase in mortality and mortality-arrhythmia with HCQ or HCQ-AZ.
Supporting Information The following supporting information is available in the online version of this paper:
References
Alkhouli, Bates, Bhatt, Sex differences in COVID-19 case fatality rate: insights from a multinational registry, Mayo Clin Proc
Arshad, Kilgore, Chaudhry, Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19, Int J Infect Dis
Bessiere, Roccia, Deliniere, Assessment of QT intervals in a case series of patients with coronavirus disease 2019 (COVID-19) infection treated with hydroxychloroquine alone or in combination with azithromycin in an intensive care unit, JAMA Cardiol
Boulware, Pullen, Bangdiwala, A Randomized trial of hydroxychloroquine as postexposure prophylaxis for Covid-19, N Engl J Med
Catteau, Dauby, Montourcy, Low-dose hydroxychloroquine therapy and mortality in hospitalized patients with COVID-19: a nationwide observational study of 8075 participants, Int J Antimicrob Agents
Cavalcanti, Zampieri, Rosa, Hydroxychloroquine with or without azithromycin in mild-to-moderate Covid-19, N Engl J Med,
doi:10.1056/NEJMoa2019014Chugh, Reinier, Singh, Determinants of prolonged QT interval and their contribution to sudden death risk in coronary artery disease: the Oregon Sudden Unexpected Death Study, Circulation
Feldmann, Maini, Woody, Trials of anti-tumour necrosis factor therapy for COVID-19 are urgently needed, Lancet
Gao, Hu, Update on use of chloroquine/hydroxychloroquine to treat coronavirus disease 2019 (COVID-19), Biosci Trends
Gao, Tian, Yang, Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies, Biosci Trends
Gautret, Lagier, Parola, Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an openlabel non-randomized clinical trial, Int J Antimicrob Agents
Geleris, Sun, Platt, Observational study of hydroxychloroquine in hospitalized patients with Covid-19, N Engl J Med
Giudicessi, Noseworthy, Friedman, Ackerman, Urgent guidance for navigating and circumventing the QTcprolonging and torsadogenic potential of possible pharmacotherapies for coronavirus disease 19 (COVID-19), Mayo Clin Proc
Imbens, Db, Casual Inference for Statistics, Social, and Biomedical Sciences: An Introduction
Kapoor, Pharmacovigilance Memorandum Department of Health and Human Services
Lane, Weaver, Kostka, Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study, Lancet Rheumatol
Magagnoli, Narendran, Pereira, Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19, medRxiv,
doi:10.1101/2020.04.16.20065920Mercuro, Yen, Shim, Risk of QT interval prolongation associated with use of hydroxychloroquine with or without concomitant azithromycin among hospitalized patients testing positive for coronavirus disease 2019 (COVID-19), JAMA Cardiol
Mousa, Broce, Bd, Cardiovascular disease novel coronavirus and the search for investigational therapies
Normand, The RECOVERY platform
Risch, Opinion: early outpatient treatment of symptomatic, high-risk Covid-19 patients that should be ramped-up immediately as key to the pandemic crisis, Am J Epidemiol
Roden, Predicting drug-induced QT prolongation and torsades de pointes, J Physiol
Rosenberg, Dufort, Udo, Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York State, JAMA
Savarino, Boelaert, Cassone, Majori, Cauda, Effects of chloroquine on viral infections: an old drug against today's diseases?, Lancet Infect Dis
Simpson, Kovacs, Stecker, Ventricular arrhythmia risk due to hydroxychloroquine-azithromycin treatment for COVID-19, Cardiol Mag
Skipper, Pastick, Engen, Hydroxychloroquine in nonhospitalized adults with early COVID-19: a randomized trial, Ann Intern Med
Stapff, Use of electronic health data in clinical development, Pharm Ind
Touret, De Lamballerie, Of chloroquine and COVID-19, Antiviral Res
Vincent, Bergeron, Benjannet, Chloroquine is a potent inhibitor of SARS coronavirus infection and spread, Virol J
Yoshida, Solomon, Kim, Active-comparator design and new-user design in observational studies, Nat Rev Rheumatol
