Non-steroidal anti-inflammatory drug use is associated with increased risk of out-of-hospital cardiac arrest: a nationwide case-time-control study

AIMS: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used and have been associated with increased cardiovascular risk. Nonetheless, it remains unknown whether use of NSAIDs is associated with out-of-hospital cardiac arrest (OHCA).

METHODS AND RESULTS: From the nationwide Danish Cardiac Arrest Registry, all persons with OHCA during 2001-2010 were identified. NSAID use 30 days before OHCA was categorized as follows: diclofenac, naproxen, ibuprofen, rofecoxib, celecoxib, and other. Risk of OHCA associated with use of NSAIDs was analyzed by conditional logistic regression in case-time-control models matching four controls on sex and age per case to account for variation in drug utilization over time.We identified 28 947 persons with OHCA of whom 3376 were treated with an NSAID up to 30 days before OHCA. Ibuprofen and diclofenac were the most commonly used NSAIDs and represented 51.0% and 21.8% of total NSAID use, respectively. Use of diclofenac (odds ratio (OR), 1.50 [95% confidence interval (CI) 1.23-1.82]) and ibuprofen (OR, 1.31 [95% CI 1.14-1.51]) was associated with a significantly increased risk of OHCA. Use of naproxen (OR, 1.29 [95% CI 0.77-2.16]), celecoxib (OR, 1.13 [95% CI 0.74-1.70]) and rofecoxib (OR, 1.28 [95% CI 0.74-1.70]) was not significantly associated with increased risk of OHCA; however, these groups were characterized by few events.

CONCLUSION: Use of non-selective NSAIDs was associated with an increased early risk of OHCA. The result was driven by an increased risk of OHCA in ibuprofen and diclofenac users.