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    Original Investigation
    Infectious Diseases
    July 1, 2020

    Association of Nonsteroidal Anti-inflammatory Drug Use and Adverse Outcomes Among Patients Hospitalized With Influenza

    Author Affiliations
    • 1Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark
    • 2Department of Clinical Biochemistry and Clinical Pharmacology, Odense University Hospital, Odense, Denmark
    • 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
    • 4Center for Population Health and Sciences, Stanford University, Stanford, California
    • 5Department of Medical Evaluation and Biostatistics, Danish Medicines Agency, Copenhagen, Denmark
    • 6Statens Serum Institut, Copenhagen, Denmark
    • 7Department of Public Health–Biostatistics, Aarhus University, Aarhus, Denmark
    • 8Department of Clinical Microbiology, Aarhus University Hospital, Aarhus, Denmark
    • 9Department of Anaesthesia and Intensive Care Medicine, Aarhus University Hospital, Aarhus, Denmark
    • 10Hospital Pharmacy Funen, Odense University Hospital, Odense, Denmark
    JAMA Netw Open. 2020;3(7):e2013880. doi:10.1001/jamanetworkopen.2020.13880
    Key Points español 中文 (chinese)

    Question  Is exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) associated with increased risk of intensive care unit admission or death among patients hospitalized with influenza?

    Findings  In this Danish nationwide cohort study that included 7747 adults aged 40 years or older, no association of NSAID use with intensive care unit admission or 30-day mortality was found.

    Meaning  The findings of this study suggest that among patients hospitalized with influenza, those who use NSAIDs do not have worse prognosis than those with no NSAID use.


    Importance  During the ongoing coronavirus disease 2019 pandemic, case reports have suggested that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may lead to adverse outcomes.

    Objective  To study the association of NSAID use with adverse outcomes in patients hospitalized with influenza or influenza pneumonia.

    Design, Setting, and Participants  This cohort study used propensity score matching among 7747 individuals aged 40 years or older who were hospitalized with influenza, confirmed by polymerase chain reaction or antigen testing, between 2010 and 2018. Data were collected using Danish nationwide registers. All analyses reported were performed on May 29, 2020.

    Exposures  Prescription fill of an NSAID within 60 days before admission.

    Main Outcomes and Measures  Risk ratio (RR) and risk difference (RD) with 95% CIs for intensive care unit admission and death within 30 days of admission.

    Results  A total of 7747 patients (median [interquartile range] age, 71 [59-80] years, 3980 [51.4%] men) with confirmed influenza were identified. Of these, 520 (6.7%) were exposed to NSAIDs. In the unmatched cohorts, 104 of 520 patients (20.0%) who used NSAIDs and 958 of 7227 patients (13.3%) who did not use NSAIDs were admitted to the intensive care unit. For death within 30 days of admission, we observed 37 events (7.1%) among those who used NSAIDs compared with 563 events (7.8%) among those who did not. Current NSAID use was associated with intensive care unit admission (RR, 1.51; 95% CI, 1.26 to 1.81; RD, 6.7%; 95% CI, 3.2% to 10.3%), while NSAID use was not associated with death (RR, 0.91; 95% CI, 0.66 to 1.26; RD, –0.7%; 95% CI, –3.0% to 1.6%). In the matched cohorts, risks were unchanged for patients who used NSAIDs, while 83 ICU admissions (16.0%) and 36 deaths (6.9%) were observed among matched individuals who did not use NSAIDs. Matched (ie, adjusted) analyses yielded attenuated risk estimates for intensive care unit admission (RR, 1.25; 95% CI, 0.95 to 1.63; RD, 4.0%; 95% CI, –0.6% to 8.7%) and death (RR, 1.03; 95% CI, 0.66 to 1.60; RD, 0.2%; 95% CI, –2.9% to 3.3%). Associations were more pronounced among patients who used NSAIDs for a longer period (eg, for intensive care unit admission: RR, 1.90; 95% CI, 1.19 to 3.06; RD, 13.4%; 95% CI, 4.0% to 22.8%).

    Conclusions and Relevance  In this cohort study of adult patients hospitalized with influenza, the use of NSAIDs was not associated with 30-day intensive care unit admission or death in adjusted analyses. There was an association between long-term use of NSAIDs and intensive care unit admission.