Exploring the Cardiovascular Safety Profile of Ibuprofen: Insights from EudraVigilance Database

Background: Ibuprofen is one of the most accessible non-steroidal anti-inflammatory drugs (NSADs), exhibiting non-selective reversible inhibition on COX-1 and COX-2. A series of common adverse reactions have been mentioned through the years: gastrointestinal (gastritis, ulceration, hemorrhage, or perforation), renal, hematologic, and cardiovascular. Objective: The aim of this study was to assess the real-world impact of ibuprofen regarding cardiovascular safety, utilizing an established pharmacovigilance database. Methods: Descriptive and disproportionality-based methods were used. Forty specific descriptors of cardiovascular effects were selected. Eight other NSADs and the combination of ibuprofen and pseudoephedrine were used as comparators. Results: A total of 58,760 cases were identified as being associated with ibuprofen in EudraVigilance. Stroke was reported for ibuprofen with a lower probability compared with etoricoxib (ROR: 0.34; 95% CI: 0.21-0.55), celecoxib (ROR: 0.07; 95% CI: 0.06-0.10), meloxicam (ROR: 0.25; 95% CI: 0.14-0.43), acetylsalicylic acid (ROR: 0.07; 95% CI: 0.05-0.09), and ibuprofen/pseudoephedrine (ROR: 0.11; 95% CI: 0.05-0.25). Thrombosis was reported for ibuprofen with a higher probability only relative to ketoprofen (ROR: 2.95; 95% CI: 1.71-5.09). Hypertension was reported for ibuprofen as being more probable than for acetylsalicylic acid (ROR: 1.58; 95% CI: 1.43-1.76). Myocardial infarction was reported as being more probable for ibuprofen than ketoprofen (ROR: 2.31; 95% CI: 1.57-3.40) or nimesulide (ROR: 2.43; 95% CI: 1.25-4.73). Conclusions: Overall, according to our study, the probability of reported cardiovascular adverse reactions is lower than those determined for the rest of the NSAIDs; however, taking into consideration the inherent limitations of the study, further clinical investigations would contribute to a better understanding of the cardiovascular safety of ibuprofen.