Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen and relationship with mortality among United States Veterans after testing positive for COVID-19
Heather M Campbell, Allison E Murata, Todd A Conner, Greg Fotieo
PLOS ONE, doi:10.1371/journal.pone.0267462
Non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are among the mostfrequently used medications. Although these medications have different mechanisms of action, they have similar indications and treatment duration has been positively correlated with cardiovascular risk although the degree of risk varies by medication. Our objective was to study treatment effects of chronic use of individual NSAID medications and acetaminophen on all-cause mortality among patients who tested positive for COVID-19 while accounting for adherence. We used the VA national datasets in this retrospective cohort study to differentiate between sporadic and chronic medication use: sporadic users filled an NSAID within the last year, but not recently or regularly. Using established and possible risk factors for severe COVID-19, we used propensity scores analysis to adjust for differences in baseline characteristics between treatment groups. Then, we used multivariate logistic regression incorporating inverse propensity score weighting to assess mortality. The cohort consisted of 28,856 patients. Chronic use of aspirin, ibuprofen, naproxen, meloxicam, celecoxib, diclofenac or acetaminophen was not associated with significant differences in mortality at 30 days (
take these medications chronically is no different than patients who sporadically used NSAIDs. This information can also be used by clinicians caring for patients as they make clinical treatment decisions based on their risk assessment. Our attempt to address this was by controlling the month or season in which patients tested positive: with an unadjusted OR = 0.90 and OR = 0.91 for 30-day and 60-day mortality, respectively, month did not meet the criteria for a moderate association to be included in the final propensity score-adjusted model. With season having OR = 0.66 and OR = 0.68 for 30-and 60-day mortality, respectively, it also did not meet the criteria of OR = 0.50 to be included.
References
Andersohn, Suissa, Garbe, Use of first-and second-generation cyclooxygenase-2-selective nonsteroidal antiinflammatory drugs and risk of acute myocardial infarction, Circulation,
doi:10.1161/CIRCULATIONAHA.105.602425Arnold, CDW date of death analysis and vital status file comparison update
Asadi, Sayar, Radmanesh, Naghshi, Mousaviasl et al., Efficacy of naproxen in the management of patients hospitalized with COVID-19 infection: a randomized, double-blind, placebocontrolled clinical trial, Diabetes Metab Syndr,
doi:10.1016/j.dsx.2021.102319Austin, Grootendorst, Anderson, A comparison of the ability of different propensity score models to balance measured variables between treated and untreated subjects: a Monte Carlo study, Stat Med,
doi:10.1002/sim.2580Bhala, Emberson, Merhi, Abramson, Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials, Lancet,
doi:10.1016/S0140-6736%2813%2960900-9Bruce, Barlow-Pay, Short, Vilches-Moraga, Price et al., Prior routine use of non-steroidal anti-inflammatory drugs (NSAIDs) and important outcomes in hospitalised patients with COVID-19, J Clin Med
Chan, Manson, Albert, Chae, Rexrode et al., Nonsteroidal antiinflammatory drugs, acetaminophen, and the risk of cardiovascular events, Circulation,
doi:10.1161/CIRCULATIONAHA.105.595793Chandan, Zemedikun, Thayakaran, Byne, Dhalla et al., Non-steroidal anti-inflammatory drugs and susceptibility to COVID-19, Arthritis Rheumatol,
doi:10.1002/art.41593Chmiel, Konstan, Accurso, Lymp, Mayer-Hamblett et al., Use of ibuprofen to assess inflammatory biomarkers in induced sputum: Implications for clinical trials in cystic fibrosis, J Cyst Fibros,
doi:10.1016/j.jcf.2015.03.007Chow, Khanna, Kethireddy, Yamane, Levine et al., Aspirin use is associated with decreased mechanical ventilation, intensive care unit admission, and in-hospital mortality in hospitalized patients with Coronavirus Disease 2019, Anesth Analg,
doi:10.1213/ANE.0000000000005292Eeren, Spreeuwenberg, Bartak, De Rooij, Busschbach, Estimating subgroup effects using the propensity score method: a practical application in outcomes research, Med Care,
doi:10.1097/MLR.0000000000000325Esba, Alqahtani, Thomas, Shamas, Alswaidan et al., Ibuprofen and NSAID use in COVID-19 infected patients is not associated with worse outcomes: a prospective cohort study, Infect Dis Ther,
doi:10.1007/s40121-020-00363-wGallelli, Galasso, Falcone, Southworth, Greco et al., The effects of nonsteroidal anti-inflammatory drugs on clinical outcomes, synovial fluid cytokine concentration and signal transduction pathways in knee osteoarthritis. A randomized open label trial, Osteoarthritis Cartilage,
doi:10.1016/j.joca.2013.06.026Giollo, Adami, Gatti, Idolazzi, Rossini, Coronavirus disease 19 (Covid-19) and non-steroidal anti-inflammatory drugs (NSAID), Ann Rheum Dis,
doi:10.1136/annrheumdis-2020-217598Helin-Salmivaara, Virtanen, Vesalainen, Gronroos, Klaukka et al., NSAID use and the risk of hospitalization for first myocardial infarction in the general population: a nationwide case-control study from Finland, Eur Heart J,
doi:10.1093/eurheartj/ehl053Hong, Chen, You, Tan, Wu et al., Celebrex adjuvant therapy on Coronavirus Disease 2019: an experimental study, Front Pharmacol,
doi:10.3389/fphar.2020.561674Jeong, Lee, Shin, Choe, Filion et al., Association between NSAIDs use and adverse clinical outcomes among adults hospitalized with COVID-19 in South Korea: A nationwide study, Clin Infect Dis,
doi:10.1093/cid/ciaa1056Kragholm, Gerds, Fosbol, Andersen, Phelps et al., Association between prescribed ibuprofen and severe COVID-19 infection: a nationwide register-based cohort study, Clin Transl Sci,
doi:10.1111/cts.12904Lund, Kristensen, Reilev, Christensen, Thomsen et al., Adverse outcomes and mortality in users of non-steroidal anti-inflammatory drugs who tested positive for SARS-CoV-2: A Danish nationwide cohort study, PLoS Med,
doi:10.1371/journal.pmed.1003308Meizlish, Goshua, Liu, Fine, Amin et al., Intermediate-dose anticoagulation, aspirin, and in-hospital mortality in COVID-19: A propensity score-matched analysis, Am J Hematol,
doi:10.1002/ajh.26102Nguyen, Collins, Spence, Daures, Devereaux et al., Double-adjustment in propensity score matching analysis: choosing a threshold for considering residual imbalance, BMC Med Res Methodol,
doi:10.1186/s12874-017-0338-0Osborne, Veigulis, Arreola, Mahajan, Roosli et al., Association of mortality and aspirin prescription for COVID-19 patients at the Veterans Health Administration, PLoS One,
doi:10.1371/journal.pone.0246825Petersen, Porter, Gruber, Wang, Van Der Laan, Diagnosing and responding to violations in the positivity assumption, Stat Methods Med Res,
doi:10.1177/0962280210386207Rosenbaum, Propsensity score
Sahai, Bhandari, Godwin, Mcintyre, Chung et al., Effects of aspirin on shortterm outcomes in hospitalized patients with COVID-19, Vasc Med,
doi:10.1177/1358863X211012754Sahai, Bhandari, Koupenova, Freedman, Godwin et al., SARS-CoV-2 receptors are expressed on human platelets and the effect of aspirin on clinical outcomes in COVID-19 patients, Res Sq,
doi:10.21203/rs.3.rs-119031/v1Schmidt, Christiansen, Mehnert, Rothman, Sorensen, Non-steroidal anti-inflammatory drug use and risk of atrial fibrillation or flutter: population based case-control study, BMJ,
doi:10.1136/bmj.d3450Schmidt, Lamberts, Olsen, Fosboll, Niessner et al., Cardiovascular safety of non-aspirin non-steroidal anti-inflammatory drugs: review and position paper by the working group for Cardiovascular Pharmacotherapy of the European Society of Cardiology, Eur Heart J,
doi:10.1093/eurheartj/ehv505Son, Noh, Lee, Seo, Park et al., Effect of aspirin on coronavirus disease 2019: a nationwide case-control study in South Korea, Medicine,
doi:10.1097/MD.0000000000026670United, States Food and Drug Administration. FDA advises patients on use of non-steroidal anti-inflammatory drugs (NSAIDs) for COVID-19
Wong, Mackenna, Morton, Schultze, Walker et al., Use of non-steroidal anti-inflammatory and risk of death from COVID-19: an OpenSAFELY cohort analysis based on two cohorts, BMJ,
doi:10.1136/annrheumdis-2020-219517Wong, Wang, Liu, Hebert, Maciejewski, Do Veterans Health Administration enrollees generalize to other populations?, Med Care Res Rev,
doi:10.1177/1077558715617382Zhao, Gao, Dai, Treggiari, Deshpande et al., Treatments associated with lower mortality among critially ill COVID-19 patients: a retrospective cohort study, Anesthesiology,
doi:10.1097/ALN.0000000000003999
