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

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.

Adverse outcomes and mortality in users of non-steroidal anti-inflammatory drugs who tested positive for SARS-CoV-2: A Danish nationwide cohort study

“…Third, the adverse effects of NSAIDs on the course of pneumonia may be specific to bacterial infections. A recent study on the risk of adverse outcomes in users of NSAIDs hospitalized for influenza found no association between use of NSAIDs and ICU admission or death [9], similar to the findings in this study.…”

“…Ideally, confounding by indication would be mitigated using an active comparator; however, a suitable active comparator does not exist for ibuprofen. In a previous study, users of paracetamol differed more from NSAID users than did non-users of NSAIDs [9].…”

“…The available evidence stems mainly from studies on community-acquired bacterial pneumonia and shows that use of NSAIDs is associated with bacterial complications, specifically empyema and lung abscesses [ 4 – 7 ]. For viral illness, use of NSAIDs was not associated with mortality in intensive care unit (ICU) patients with influenza H1N1 during the 2009 pandemic [ 8 ], and a recent study found that use of NSAIDs was not associated with mortality in patients hospitalized for influenza [ 9 ]. As use of ibuprofen and other NSAIDs is widespread, data on their safety are urgently needed to guide clinicians and patients on how to use NSAIDs during the COVID-19 pandemic.…”

Adverse Outcomes and Mortality in Users of Non-Steroidal Anti-Inflammatory Drugs tested positive for SARS-CoV-2: A Danish Nationwide Cohort Study

“…The available evidence stems mainly from studies on community acquired bacterial pneumonia and show that use of NSAIDs is associated with bacterial complications, specifically empyema and lung abscesses (4)(5)(6)(7). For viral illness, use of NSAIDs was not associated with mortality in ICU patients with influenza H1N1 during the 2009 pandemic (8), and a recent study found that use of NSAIDs was not associated with mortality in patients hospitalized for influenza (9). As use of ibuprofen and other NSAIDs is widespread, data on its safety is urgently needed to guide clinicians and patients on how to use NSAIDs during the COVID-19 pandemic.…”

COVID-19 and NSAIDs: Primum non nocere

“…But, taken together, along with the pharmacovigilance cases, the experimental studies and the pharmacological plausibility, we do believe that all these complementary data constitute a solid range of converging clinical and scientific evidence supporting an increased risk of severe bacterial complications under NSAIDs. Moreover, Pottegard et al have also recently observed in a nationwide population-based cohort study of patients with confirmed influenza or influenza-related pneumonia, an increased risk of pleuro-pulmonary complications for NSAID users [4] .…”