Topical vs Oral NSAIDs for Rheumatoid Arthritis: Examining Cardiovascular Risks

topical NSAID
topical NSAID
Researchers assessed the rates of composite cardiovascular events in people with RA using NSAIDs to treat musculoskeletal pain.

The use of topical nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a lower risk for composite cardiovascular (CV) events compared with the use of oral nonselective NSAIDs in patients with rheumatoid arthritis (RA), according to results of a retrospective cohort study published in the Journal of the American Heart Association.

Researchers enrolled 46,017 patients >18 years of age with RA were in the study. A total of 10,758 and 78,056 topical and oral NSAID treatment episodes, respectively, were identified from this patient cohort. On average, 2 episodes of re-initiation of therapy per patient were reported during the follow-up period. 

NSAID exposures continued until the occurrence of a treatment gap of more than 30 days. The main study outcome was the composite of  CV events, including myocardial infarction, unstable angina, heart failure, stroke, and revascularization.

Crude CV event rates were 1.83 per 100 person-years in the topical nonselective NSAID arm and 2.14 per 100 person-years in the oral nonselective NSAID arm. Based on the Kaplan-Meier survival curve, a trend toward significantly higher event-free survival during follow-up was reported in the topical nonselective NSAID group (P =.25 for log-rank test). 

A lower risk for composite CV events was demonstrated among topical NSAID users compared with oral NSAID users, with both inverse probability of treatment weight (hazard ratio [HR], 0.64; 95% CI, 0.43-0.95) and multivariable Cox regression models (HR, 0.54; 95% CI, 0.37-0.77).

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The investigators concluded that if future studies with larger sample sizes, more events, and longer-term follow-up periods confirm these results, NSAID prescribing patterns might be adapted accordingly. 

Moreover, head-to-head comparisons of different formulations within topical NSAIDs (gels, ointments, and patches) are warranted.

Disclosures: Dr Solomon receives salary support from grants to Brigham and Women’s Hospital from Pfizer, Eli Lilly, Amgen, Bristol Myers Squibb, and Genentech. Dr Solomon also served without pay on the executive committee of a large NSAID trial funded by Pfizer, and receives royalties from his work on chapters in UpToDate about NSAIDs.


Lin T-C, Solomon DH, Tedeschi SK, Yoshida K, Kao Yang Y-H. Comparative risk of cardiovascular outcomes between topical and oral nonselective NSAIDs in Taiwanese patients with rheumatoid arthritis. J Am Heart Assoc. 2017;6(11):e006874.