Renal effects of selective cyclooxygenase-2 inhibitor anti-inflammatory drugs: A systematic review and meta-analysis

Background

Selective cyclooxygenase-2 inhibitor anti-inflammatory drugs (coxibs) are associated with the development of adverse events, mainly gastrointestinal and cardiovascular, but renal effects are less known.

Objective

To assess the renal risks of coxibs compared to placebo by means of a systematic review and meta-analysis.

Methods

Randomized controlled trials that assessed renal effects of coxibs (celecoxib, etoricoxib, lumiracoxib, parecoxib, and valdecoxib) were searched in PubMed, Embase, Scopus and other sources up to March 2024. Two independent reviewers performed study screening, data extraction, and risk of bias assessment. Random effect meta-analysis was employed to calculate the relative risks (RR) and 95% confidence intervals (CI) of renal effects of coxibs compared to placebo and inconsistency among studies (I²). Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.

Results

Out of 5284 retrieved records, 49 studies (comprising 46 reports) were included. Coxibs increased the risk of edema (RR 1.46; 95% CI 1.15, 1.86; I² = 0%; 34 studies, 19,754 participants; moderate-certainty evidence), and celecoxib increased hypertensive or renal events (RR 1.24; 95% CI 1.08, 1.43; I² = 0%; 2 studies, 3589 participants; moderate-certainty evidence). Etoricoxib increased the risk of hypertension (RR 1.98; 95% CI 1.14, 3.46; I² = 34%; 13 studies, 6560 participants; moderate-certainty evidence); no difference was observed when pooling all coxibs (RR 1.26; 95% CI 0.91, 1.76; I² = 26%; 30 studies, 16,173 participants; moderate-certainty evidence).

Conclusions

Coxibs likely increase the renal adverse effects, including hypertension and edema. Awareness about the renal risks of coxibs should be increased, mainly in high-risk patient.