Association Between Prescribed Ibuprofen and Severe COVID‐19 Infection: A Nationwide Register‐Based Cohort Study

Kragholm, Kristian; Gerds, Thomas A.; Fosbøl, Emil; Porsborg Andersen, Mikkel; Phelps, Matthew; Butt, Jawad H.; Østergaard, Lauge; Bang, Casper N.; Pallisgaard, Jannik; Gislason, Gunnar; Schou, Morten; Køber, Lars; Torp‐Pedersen, Christian

Recommendations regarding ibuprofen use in relation to coronavirus disease 2019 (COVID‐19) have been conflicting. We examined risk of severe COVID‐19 between ibuprofen‐prescribed and non‐ibuprofen COVID‐19 patients in a nationwide register‐based study of COVID‐19 patients in Denmark between end of February 2020 and May 16, 2020. Patients with heart failure (n=208), <30 years (n=575), and prescribed other non‐steroidal anti‐inflammatory drugs (n=57) were excluded. Patients with ibuprofen prescription claims between January 1, 2020, and before COVID‐19 diagnosis or April 30, 2020 (last available prescription) were compared to patients without ibuprofen prescription claims. Outcome was a 30‐day composite of severe COVID‐19 diagnosis with acute respiratory syndrome, intensive care unit admission, or death. Absolute risks and average risk ratios comparing outcome for ibuprofen versus non‐ibuprofen patients standardized to the age, sex, and comorbidity distribution of all patients were derived from multivariable Cox regression. Among 4,002 patients, 264 (6.6%) had ibuprofen prescription claims before COVID‐19. Age, sex and comorbidities were comparable between the two study groups. Standardized absolute risks of the composite outcome for ibuprofen‐prescribed versus non‐ibuprofen patients were 16.3% [95% CI 12.1‐20.6] versus 17.0% [95% CI 16.0‐18.1], P=0.74. The standardized average risk ratio for ibuprofen‐prescribed versus non‐ibuprofen patients was 0.96 [95% CI 0.72‐1.23]. Standardized absolute risks of the composite outcome for patients with ibuprofen prescription claims >14 days before COVID‐19 versus ≤14 days of COVID‐19 were 17.1% [95% CI 12.3‐22.0] versus 14.3% [95% CI 7.1‐23.1]. In conclusion, in this nationwide study, there was no significant association between ibuprofen prescription claims and severe COVID‐19.