Comparative Risk of Cardiovascular Outcomes Between Topical and Oral Nonselective NSAIDs in Taiwanese Patients With Rheumatoid Arthritis

BACKGROUND: Topical NSAIDs have less systemic absorption than oral NSAIDs. We examined the risk of cardiovascular events associated with nonselective topical NSAIDs versus oral NSAIDs among patients with rheumatoid arthritis in Taiwan. METHODS AND RESULTS: We conducted a retrospective cohort study that included patients with incident rheumatoid arthritis who were newly starting therapy with nonselective topical NSAIDs or oral NSAIDs. We used the Taiwan National Health Insurance Research Database (NHIRD). The first date patients received either type of NSAID was defined as the index date. NSAID exposures continued until there was a treatment gap of >30 days. The main outcome was composite cardiovascular events, including myocardial infarction, unstable angina, heart failure, stroke, or revascularization. Follow‐up was censored at treatment discontinuation, switch or addition of other NSAID category, cardiovascular outcome, death, or the end of the study. Propensity score weighted Cox regression models were used to compare the risk of cardiovascular events between topical NSAIDs and oral NSAIDs. There were 10 758 and 78 056 treatment episodes for topical and oral NSAIDs identified. After weighting by propensity score, the cohorts were well balanced over all covariates. The crude cardiovascular event rate was 1.87 per 100 person‐years for topical NSAIDs and 2.14 per 100 person‐years for oral NSAIDs. Results of propensity score weighted Cox regression found the topical NSAID group had 36% lower risk for cardiovascular events compared with the oral NSAID group (hazard ratio, 0.64; 95% confidence interval, 0.43–0.95). CONCLUSIONS: We found topical NSAID users experienced a reduced risk of cardiovascular events compared with oral NSAID users. If future studies with a larger sample size and longer follow‐up confirm these results, NSAID prescribing might change accordingly.