Heterogeneity and temporal variation in the management of COVID-19: a multinational drug utilization study including 71,921 hospitalized patients from China, South Korea, Spain, and the United States of America
Prats-Uribe A., G. Sena A., Yin Hui Lai L., Ahmed W-U-R., Alghoul H., Alser O., Alshammari TM., Areia C., Carter W., Casajust P., Dawoud D., Golozar A., Jonnagaddala J., Mehta P., Menchung G., Morales DR., Nyberg F., Posada JD., Recalde M., Roel E., Shah K., Shah N., Schilling LM., Subbian V., Vizcaya D., Williams A., Zhang L., Zhang Y., Zhu H., Liu L., Rijnbeek P., Hripcsak G., Lane JCE., Burn E., Reich C., Suchard MA., Duarte-Salles T., Kostka K., Ryan PB., PRIETO-ALHAMBRA D.
<jats:p>Objectives: A plethora of medicines have been repurposed or used as adjunctive therapies for COVID-19. We characterized the utilization of medicines as prescribed in routine practice amongst patients hospitalized for COVID-19 in South Korea, China, Spain, and the USA. Design: International network cohort Setting: Hospital electronic health records from Columbia University Irving Medical Centre (NYC, USA), Stanford (CA, USA), Tufts (MA, USA), Premier (USA), Optum EHR (USA), department of veterans affairs (USA), NFHCRD (Honghu, China) and HM Hospitals (Spain); and nationwide claims from HIRA (South Korea) Participants: patients hospitalized for COVID-19 from January to June 2020 Main outcome measures: Prescription/dispensation of any medicine on or 30 days after hospital admission date Analyses: Number and percentage of users overall and over time Results: 71,921 people were included: 304 from China, 2,089 from Spain, 7,599 from South Korea, and 61,929 from the USA. A total of 3,455 medicines were identified. Common repurposed medicines included hydroxychloroquine (<2% in NFHCRD to 85.4% in HM), azithromycin (4.9% in NFHCRD to 56.5% in HM), lopinavir/ritonavir (<3% in all US but 34.9% in HIRA and 56.5% in HM), and umifenovir (0% in all except 78.3% in NFHCRD). Adjunctive medicines were used with great variability, with the ten most used treatments being (in descending order): bemiparin, enoxaparin, heparin, ceftriaxone, aspirin, vitamin D, famotidine, vitamin C, dexamethasone, and metformin. Hydroxychloroquine and azithromycin increased rapidly in use in March-April but declined steeply in May-June. Conclusions: Multiple medicines were used in the first months of COVID-19 pandemic, with substantial geographic and temporal variation. Hydroxychloroquine, azithromycin, lopinavir-ritonavir, and umifenovir (in China only) were the most prescribed repurposed medicines. Antithrombotics, antibiotics, H2 receptor antagonists and corticosteroids were often used as adjunctive treatments. Research is needed on the comparative risk and benefit of these treatments in the management of COVID-19.</jats:p>