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PLoS Med: Adverse Outcomes & Mortality in NSAID Users With SARS-CoV-2 - Denmark
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Nearly 6 months ago - in mid-March - we looked at a twitter announcement (below) made by France's Health Minister warning of a possible health risk of taking anti-inflammatory drugs (including NSAIDs) while infected with SARS-CoV-2, the virus that causes COVID-19.
NSAIDs, and other anti-inflammatory drugs (including synthetic corticosteroids), are linked to a wide range of side effects. For NSAIDs - even those available over-the-counter (OTC) - there is a heightened risk of cardiovascular events and bleeding (see FDA Strengthens Warnings Of Cardiovascular Risks With NSAIDs), while in the case of corticosteroids, of lowered immunity to infections.
While there was no solid evidence back in March linking the use of NSAIDs to worse outcomes with COVID-19, within days (see The NSAIDs & COVID-19 Debate Revisited) several public health agencies and medical journals (including the WHO, the UK's NHS and the BMJ) advised against their use until more was known.
A little more than a month later (mid-April) the World Health Organization released a preliminary Scientific Brief on the use of NSAIDs with COVID-19 - and while data was limited - they could find no evidence of severe adverse events as a result of the use of NSAIDs in COVID-19 patients.
Gradually concerns over NSAIDs dwindled, but since an absence of evidence is not necessarily evidence of absence, researchers in Denmark embarked on a mission to further clarify matters by conducting a nationwide cohort study.
Note: The availability of OTC NSAIDS is limited in Denmark (only Ibuprofen, and only sold in small packages (20 ct.) of 200 mg dosages) due concerns over cardiovascular risks. This study was based on those who filled NSAID prescriptions within 30 days of a positive SARS-CoV-2 test.
The good news is, after examining the outcomes and NSAID usage of nearly 10,000 COVID-19 cases, the authors have concluded that NSAID use was not associated with increased 30-day mortality or adverse outcomes.
Some excerpts from the open-access research study follow, but click the link to read it in its entirety.
RESEARCH ARTICLE
Adverse outcomes and mortality in users of non-steroidal anti-inflammatory drugs who tested positive for SARS-CoV-2: A Danish nationwide cohort study
Lars Christian Lund ,Kasper Bruun Kristensen ,Mette Reilev, Steffen Christensen, Reimar Wernich Thomsen, Christian Fynbo Christiansen, Henrik St?vring, Nanna Borup Johansen, Nikolai Constantin Brun, Jesper Hallas, Anton Potteg?rd
The main outcome was 30-day mortality, and NSAID users were compared to non-users using risk ratios (RRs) and risk differences (RDs). Secondary outcomes included hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and acute renal replacement therapy. A total of 9,236 SARS-CoV-2 PCR-positive individuals were eligible for inclusion. The median age in the study cohort was 50 years, and 58% were female. Of these, 248 (2.7%) had filled a prescription for NSAIDs, and 535 (5.8%) died within 30 days.
In the matched analyses, treatment with NSAIDs was not associated with 30-day mortality (RR 1.02, 95% CI 0.57 to 1.82, p = 0.95; RD 0.1%, 95% CI −3.5% to 3.7%, p = 0.95), risk of hospitalization (RR 1.16, 95% CI 0.87 to 1.53, p = 0.31; RD 3.3%, 95% CI −3.4% to 10%, p = 0.33), ICU admission (RR 1.04, 95% CI 0.54 to 2.02, p = 0.90; RD 0.2%, 95% CI −3.0% to 3.4%, p = 0.90), mechanical ventilation (RR 1.14, 95% CI 0.56 to 2.30, p = 0.72; RD 0.5%, 95% CI −2.5% to 3.6%, p = 0.73), or renal replacement therapy (RR 0.86, 95% CI 0.24 to 3.09, p = 0.81; RD −0.2%, 95% CI −2.0% to 1.6%, p = 0.81).
The main limitations of the study are possible exposure misclassification, as not all individuals who fill an NSAID prescription use the drug continuously, and possible residual confounding by indication, as NSAIDs may generally be prescribed to healthier individuals due to their side effects, but on the other hand may also be prescribed for early symptoms of severe COVID-19.
Conclusions
Use of NSAIDs was not associated with 30-day mortality, hospitalization, ICU admission, mechanical ventilation, or renal replacement therapy in Danish individuals who tested positive for SARS-CoV-2.
Trial registration
Why was this study done?
What did the researchers do and find?
What do these findings mean?
(Continue . . . )
#15,455
Nearly 6 months ago - in mid-March - we looked at a twitter announcement (below) made by France's Health Minister warning of a possible health risk of taking anti-inflammatory drugs (including NSAIDs) while infected with SARS-CoV-2, the virus that causes COVID-19.
NSAIDs, and other anti-inflammatory drugs (including synthetic corticosteroids), are linked to a wide range of side effects. For NSAIDs - even those available over-the-counter (OTC) - there is a heightened risk of cardiovascular events and bleeding (see FDA Strengthens Warnings Of Cardiovascular Risks With NSAIDs), while in the case of corticosteroids, of lowered immunity to infections.
While there was no solid evidence back in March linking the use of NSAIDs to worse outcomes with COVID-19, within days (see The NSAIDs & COVID-19 Debate Revisited) several public health agencies and medical journals (including the WHO, the UK's NHS and the BMJ) advised against their use until more was known.
A little more than a month later (mid-April) the World Health Organization released a preliminary Scientific Brief on the use of NSAIDs with COVID-19 - and while data was limited - they could find no evidence of severe adverse events as a result of the use of NSAIDs in COVID-19 patients.
Gradually concerns over NSAIDs dwindled, but since an absence of evidence is not necessarily evidence of absence, researchers in Denmark embarked on a mission to further clarify matters by conducting a nationwide cohort study.
Note: The availability of OTC NSAIDS is limited in Denmark (only Ibuprofen, and only sold in small packages (20 ct.) of 200 mg dosages) due concerns over cardiovascular risks. This study was based on those who filled NSAID prescriptions within 30 days of a positive SARS-CoV-2 test.
The good news is, after examining the outcomes and NSAID usage of nearly 10,000 COVID-19 cases, the authors have concluded that NSAID use was not associated with increased 30-day mortality or adverse outcomes.
Some excerpts from the open-access research study follow, but click the link to read it in its entirety.
RESEARCH ARTICLE
Adverse outcomes and mortality in users of non-steroidal anti-inflammatory drugs who tested positive for SARS-CoV-2: A Danish nationwide cohort study
Lars Christian Lund ,Kasper Bruun Kristensen ,Mette Reilev, Steffen Christensen, Reimar Wernich Thomsen, Christian Fynbo Christiansen, Henrik St?vring, Nanna Borup Johansen, Nikolai Constantin Brun, Jesper Hallas, Anton Potteg?rd
Published: September 8, 2020
https://doi.org/10.1371/journal.pmed.1003308
https://doi.org/10.1371/journal.pmed.1003308
Abstract
Background
Concerns over the safety of non-steroidal anti-inflammatory drug (NSAID) use during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been raised. We studied whether use of NSAIDs was associated with adverse outcomes and mortality during SARS-CoV-2 infection.
Methods and findings
Background
Concerns over the safety of non-steroidal anti-inflammatory drug (NSAID) use during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been raised. We studied whether use of NSAIDs was associated with adverse outcomes and mortality during SARS-CoV-2 infection.
Methods and findings
We conducted a population-based cohort study using Danish administrative and health registries. We included individuals who tested positive for SARS-CoV-2 during the period 27 February 2020 to 29 April 2020. NSAID users (defined as individuals having filled a prescription for NSAIDs up to 30 days before the SARS-CoV-2 test) were matched to up to 4 non-users on calendar week of the test date and propensity scores based on age, sex, relevant comorbidities, and use of selected prescription drugs.
The main outcome was 30-day mortality, and NSAID users were compared to non-users using risk ratios (RRs) and risk differences (RDs). Secondary outcomes included hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and acute renal replacement therapy. A total of 9,236 SARS-CoV-2 PCR-positive individuals were eligible for inclusion. The median age in the study cohort was 50 years, and 58% were female. Of these, 248 (2.7%) had filled a prescription for NSAIDs, and 535 (5.8%) died within 30 days.
In the matched analyses, treatment with NSAIDs was not associated with 30-day mortality (RR 1.02, 95% CI 0.57 to 1.82, p = 0.95; RD 0.1%, 95% CI −3.5% to 3.7%, p = 0.95), risk of hospitalization (RR 1.16, 95% CI 0.87 to 1.53, p = 0.31; RD 3.3%, 95% CI −3.4% to 10%, p = 0.33), ICU admission (RR 1.04, 95% CI 0.54 to 2.02, p = 0.90; RD 0.2%, 95% CI −3.0% to 3.4%, p = 0.90), mechanical ventilation (RR 1.14, 95% CI 0.56 to 2.30, p = 0.72; RD 0.5%, 95% CI −2.5% to 3.6%, p = 0.73), or renal replacement therapy (RR 0.86, 95% CI 0.24 to 3.09, p = 0.81; RD −0.2%, 95% CI −2.0% to 1.6%, p = 0.81).
The main limitations of the study are possible exposure misclassification, as not all individuals who fill an NSAID prescription use the drug continuously, and possible residual confounding by indication, as NSAIDs may generally be prescribed to healthier individuals due to their side effects, but on the other hand may also be prescribed for early symptoms of severe COVID-19.
Conclusions
Use of NSAIDs was not associated with 30-day mortality, hospitalization, ICU admission, mechanical ventilation, or renal replacement therapy in Danish individuals who tested positive for SARS-CoV-2.
Trial registration
The European Union electronic Register of Post-Authorisation Studies EUPAS34734
Author summary
Author summary
Why was this study done?
During the early phases of the pandemic of coronavirus disease 2019 (COVID-19), concerns were raised that ibuprofen, a drug commonly used to treat weak pain and fevers, may lead to a more severe course of coronavirus disease.
If this risk is verified, it would be important to reduce the use of ibuprofen and ibuprofen-like drugs, commonly referred to as non-steroidal anti-inflammatory drugs (NSAIDs), among patients at risk of COVID-19.
What did the researchers do and find?
We identified all Danish residents who tested positive for the infectious agent of COVID-19 and grouped them into users and non-users of NSAIDs.
The risks of being hospitalized, admitted to the intensive care unit, or dying were compared between the 2 groups.
The risks of being hospitalized, admitted to the intensive care unit, or dying were compared between the 2 groups.
Overall, risks for all studied outcomes were similar between users and non-users of ibuprofen and other NSAIDs.
What do these findings mean?
NSAIDs do not lead to more severe coronavirus disease according to this study.
(Continue . . . )
