Nonsteroidal anti-inflammatory drugs and incidence of atrial fibrillation: a meta-analysis

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for many inflammatory disorders and pain-related illnesses. Despite their widespread use, the association between NSAIDs and the incidence of atrial fibrillation (AF) remains unclear. The aim of this systematic review and meta-analysis is to investigate this association. Methods: A systematic review was conducted in MEDLINE, EMBASE and Cochrane databases from inception through August 2019 to identify studies that evaluated the risk of AF among patients using NSAIDs. Pooled risk ratios (RRs) and 95% CI were calculated using a random-effect, generic inverse variance method. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42019141609). Results: Eight observational studies (four case-control studies and four cohort studies) with a total of 14 806 420 patients were enrolled. When compared with nonNSAIDs users, the pooled RR of AF in patients with NSAIDs use was 1.29 (95% CI 1.19-1.39). Meta-analyses based on the type of study were additionally performed. Subgroup analysis by study design revealed a significant association between the use of NSAIDs and AF for both case-control studies (pooled RR 1.37; 95% CI, 1.15-1.63) and cohort studies (pooled RR 1.22; 95% CI, 1.14-1.31). Sub-analyses based on specific NSAIDs showed pooled RRs of AF in patients using ibuprofen of 1.30 (95% CI 1.22-1.39), naproxen of 1.44 (95% CI 1.18-1.76) and diclofenac of 1.37 (95% CI 1.10-1.71), respectively. Funnel plot and Egger's regression asymmetry tests were performed and showed no publication bias. Conclusion: NSAID use is associated with incident AF. Our study also demonstrated a consistent result among different NSAIDs.