OpenSAFELY: Do adults prescribed non-steroidal anti-inflammatory drugs have an increased risk of death from COVID-19?

Angel YS Wong ORCID logo ; Brian MacKenna ORCID logo ; Caroline E Morton ORCID logo ; Anna Schultze ORCID logo ; Alex J Walker ORCID logo ; Krishnan Bhaskaran ORCID logo ; Jeremy P Brown ORCID logo ; Christopher T Rentsch ORCID logo ; Elizabeth Williamson ORCID logo ; Henry Drysdale ; +21 more... Richard Croker ORCID logo ; Seb Bacon ORCID logo ; William Hulme ; Chris Bates ORCID logo ; Helen J Curtis ORCID logo ; Amir Mehrkar ; David Evans ; Peter Inglesby ; Jonathan Cockburn ; Helen I McDonald ORCID logo ; Laurie Tomlinson ORCID logo ; Rohini Mathur ORCID logo ; Kevin Wing ORCID logo ; Harriet Forbes ORCID logo ; John Parry ; Frank Hester ; Sam Harper ; Stephen JW Evans ORCID logo ; Liam Smeeth ORCID logo ; Ian J Douglas ORCID logo ; Ben Goldacre ORCID logo ; (2020) OpenSAFELY: Do adults prescribed non-steroidal anti-inflammatory drugs have an increased risk of death from COVID-19? medRxiv preprint. 2020.08.12.20171405-. DOI: 10.1101/2020.08.12.20171405
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<jats:title>Abstract</jats:title><jats:sec><jats:title>Importance</jats:title><jats:p>There has been speculation that non-steroidal anti-inflammatory drugs (NSAIDs) may negatively affect coronavirus disease 2019 (COVID-19) outcomes, yet clinical evidence is limited.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>To assess the association between NSAID use and deaths from COVID-19 using OpenSAFELY, a secure analytical platform.</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>Two cohort studies (1<jats:sup>st</jats:sup> March-14<jats:sup>th</jats:sup> June 2020).</jats:p></jats:sec><jats:sec><jats:title>Setting</jats:title><jats:p>Working on behalf of NHS England, we used routine clinical data from &gt;17 million patients in England linked to death data from the Office for National Statistics.</jats:p></jats:sec><jats:sec><jats:title>Participants</jats:title><jats:p>Study 1: General population (people with an NSAID prescription in the last three years). Study 2: people with rheumatoid arthritis/osteoarthritis.</jats:p></jats:sec><jats:sec><jats:title>Exposures</jats:title><jats:p>Current NSAID prescription within the 4 months before 1<jats:sup>st</jats:sup> March 2020.</jats:p></jats:sec><jats:sec><jats:title>Main Outcome and Measure</jats:title><jats:p>We used Cox regression to estimate hazard ratios (HRs) for COVID-19 related death in people currently prescribed NSAIDs, compared with those not currently prescribed NSAIDs, adjusting for age, sex, comorbidities and other medications.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In Study 1, we included 535,519 current NSAID users and 1,924,095 non-users in the general population. The crude HR for current use was 1.25 (95% CI, 1.07–1.46), versus non-use. We observed no evidence of difference in risk of COVID-19 related death associated with current use (HR, 0.95, 95% CI, 0.80–1.13) in the fully adjusted model.</jats:p><jats:p>In Study 2, we included 1,711,052 people with rheumatoid arthritis/osteoarthritis, of whom 175,631 (10%) were current NSAID users. The crude HR for current use was 0.43 (95% CI, 0.36–0.52), versus non-use. In the fully adjusted model, we observed a lower risk of COVID-19 related death (HR, 0.78, 95% CI, 0.65–0.94) associated with current use of NSAID versus non-use.</jats:p></jats:sec><jats:sec><jats:title>Conclusion and Relevance</jats:title><jats:p>We found no evidence of a harmful effect of NSAIDs on COVID-19 related deaths. Risks of COVID-19 do not need to influence decisions about therapeutic use of NSAIDs.</jats:p></jats:sec>

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