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. 2020 Jul 1;3(7):e2013880.
doi: 10.1001/jamanetworkopen.2020.13880.

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

Lars Christian Lund  1 , Mette Reilev  1 , Jesper Hallas  1   2 , Kasper Bruun Kristensen  1 , Reimar Wernich Thomsen  3 , Christian Fynbo Christiansen  3 , Henrik Toft Sørensen  3   4 , Nanna Borup Johansen  5 , Nikolai Constantin Brun  5 , Marianne Voldstedlund  6 , Henrik Støvring  1   7 , Marianne Kragh Thomsen  8 , Steffen Christensen  9 , Anton Pottegård  1   10
Affiliations

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

Lars Christian Lund et al. JAMA Netw Open. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Mr Lund reported participating in research projects funded by Menarini Pharmaceutical and LEO Pharma, with funds paid to his institution (no personal fees) and with no relation to the present study. Dr Reilev reported participating in research projects funded by LEO Pharma, with funds paid to her institution (no personal fees) and with no relation to the present study. Mr Hallas reported receiving grants from Pfizer outside the submitted work. Drs R. W. Thomsen and Christiansen and Mr Sørensen reported that the Department of Clinical Epidemiology is involved in studies with funding from various companies as research grants to (and administered by) Aarhus University, none of which are related to the present study. Dr Støvring reported receiving personal fees from Bristol-Myers Squibb, Novartis, and Roche outside the submitted work. Dr Pottegård reported receiving grants from Alcon, Almirall, Astellas, Astra-Zeneca, Boehringer-Ingelheim, Novo Nordisk, Servier, and LEO Pharma outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Identification of Study Population
NSAID indicates nonsteroidal anti-inflammatory drug.
See this image and copyright information in PMC

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