Non-steroidal anti-inflammatory drug use and risk of atrial fibrillation or flutter: population based case-control study

Objectives To examine the risk of atrial fibrillation or flutter associated with use of non-selective non-steroidal anti-inflammatory drugs (NSAIDs) or selective cyclo-oxygenase (COX) 2 inhibitors. Design Population based case-control study using data from medical databases. Setting Northern Denmark (population 1.7 million). Participants 32 602 patients with a first inpatient or outpatient hospital diagnosis of atrial fibrillation or flutter between 1999 and 2008; 325 918 age matched and sex matched controls based on risk-set sampling. Main outcome measures Exposure to NSAID use at the time of admission (current use) or before (recent use). Current use was further classified as new use (first ever prescription redemption within 60 days before diagnosis date) or long term use. We used conditional logistic regression to compute odds ratios as unbiased estimates of the incidence rate ratios. Results 2925 cases (9%) and 21 871 controls (7%) were current users of either non-selective NSAIDs or COX 2 inhibitors. Compared with no use, the incidence rate ratio associating current drug use with atrial fibrillation or flutter was 1.33 (95% confidence interval 1.26 to 1.41) for non-selective NSAIDs and 1.50 (1.42 to 1.59) for COX 2 inhibitors. Adjustments for age, sex, and risk factors for atrial fibrillation or flutter reduced the incidence rate ratio to 1.17 (1.10 to 1.24) for non-selective NSAIDs and 1.27 (1.20 to 1.34) for COX 2 inhibitors. Among new users, the adjusted incidence rate ratio was 1.46 (1.33 to 1.62) for non-selective NSAIDs and 1.71 (1.56 to 1.88) for COX 2 inhibitors. Results for individual NSAIDs were similar. Conclusions Use of non-aspirin NSAIDs was associated with an increased risk of atrial fibrillation or flutter. Compared with non-users, the association was strongest for new users, with a 40-70% increase in relative risk (lowest for non-selective NSAIDs and highest for COX 2 inhibitors). Our study thus adds evidence that atrial fibrillation or flutter needs to be added to the cardiovascular risks to be considered when prescribing NSAIDs.