Comparison of cardiorenal safety of nonsteroidal anti-inflammatory drugs in the treatment of arthritis: a network meta-analysis

Background: Arthritis includes osteoarthritis (OA), rheumatoid arthritis (RA), and other arthritis-related disorders. Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most widely used drugs for the treatment of arthritis. However, there remains a concern that some currently used NSAIDs may increase the risk of cardiorenal adverse events in patients with arthritis. Although it has been established that some NSAIDs are associated with a higher risk of cardiovascular and renal events, their safety varies widely. To provide insight into drug use, this study systematically assessed and compared the incidence of cardiovascular and renal events in different NSAIDs by using Bayesian meta-analysis. Methods: The PubMed, Cochrane Library, and Embase databases were searched for randomized controlled trials (RCTs) on NSAIDs. Databases were searched from the inception to April 25, 2022. Two investigators independently screened articles according to the Population, Intervention, Comparator, Outcomes, Study design (PICOS) principle, extracted data, and assessed the quality of articles using Cochrane Risk of Bias assessing tools. R software (version 4.1.3) was used for network meta-analysis (NMA). Results: The analysis ultimately included 20 articles with a total of 144,957 patients and 13 interventions. The risk of bias in the included articles was generally moderate. Ibuprofen was associated with the highest incidence of hypertension outcomes [comparing with placebo OR (95% CI): 3.24 (1.71, 5.82)], rofecoxib with the highest incidence of renal events [comparing with placebo OR (95% CI): 4.46 (1.49, 14.73)], ibuprofen with the highest incidence of cardiovascular events [comparing with placebo OR (95% CI): 2.39 (0.82, 8.06), and naproxen with the highest incidence of edema [comparing with placebo OR (95% CI): 2.31 (1.16, 4.47)]. Conclusions: The NMA results showed that amtolmetin guacil was relatively safer, but it needs further investigation. Rofecoxib was associated with a higher incidence of cardiorenal adverse events, ibuprofen with a higher incidence of cardiovascular events and hypertension, and naproxen with a higher incidence of renal events and edema. Clinicians should weigh the efficacy of NSAIDs against renal and cardiovascular toxicity when prescribing NSAIDs for the treatment of arthritis.