NSAIDs implicated in atrial fibrillation

AARHUS, DENMARK. A group of researchers from Aarhus University Hospital and Boston University School of Public Health reports that current and long-term use of non-aspirin NSAIDs (non-selective non-steroidal anti-inflammatory drugs) and selective cyclo-oxygenase (COX) 2 inhibitors increase the risk of developing atrial fibrillation and flutter. NSAIDs such as ibuprofen, naproxen, ketoprofen and piroxicam, and COX 2 inhibitors such as diclofenac (Voltaren), celecoxib (Celebrex) and rofecoxib (Vioxx) are widely prescribed to treat inflammatory conditions and pain. Like all pharmaceutical drugs, they have the potential for serious adverse effects, in particular, gastrointestinal bleeding and renal failure.

The study involved the entire population of northern Denmark (1.7 million people). During the period January 1, 1999 to December 31, 2008, a total of 32,602 participants were diagnosed with atrial fibrillation (AF) or atrial flutter (mostly AF). The AF patients (including those with flutter) were each matched with 10 controls of the same sex and age. Thus, the 32,602 AF patients were matched with a total of 325,918 AF-free controls. The median age was 75 years and 54% were male. The prevalence of cardiovascular disease was substantially higher (80.1%) among cases than among controls (58.7%). By linking diagnosis databases with pharmacy databases (both established in Denmark in 1998), the researchers were able to correlate a diagnosis of AF with the actual use of prescription NSAIDs and COX 2 inhibitors.

They found that the incidence of AF was 46% higher among new users of NSAIDs (as compared to non-users) and 71% higher among new users of COX 2 inhibitors. New users were defined as participants who had redeemed their first ever prescription for NSAIDs or COX 2 inhibitors within 60 days of being diagnosed. The risk of developing AF increased with age and the presence of chronic kidney disease and rheumatoid arthritis. The highest risks were noted with the use of diclofenac and celecoxib, and higher-dose tablets were generally associated with higher risk than lower-dose tablets.

The researchers conclude that the use of non-aspirin NSAIDs and COX 2 inhibitors increases the risk of developing atrial fibrillation and flutter.
Schmidt, M, et al. Non-steroidal anti-inflammatory drug use and risk of atrial fibrillation or flutter. British Medical Journal, 2011 [Epub ahead of print]

Editorís comment: The first and very important comment is that the results of the study should not be interpreted as meaning that aspirin, the pharmacologic action of which is identical to that of other NSAIDs, does not increase the risk of AF. The reason why aspirin was not included in the study is that it is an over-the-counter remedy and thus not included in the database of pharmaceutical drug prescription actually redeemed. An earlier study of a group of Italian and Spanish researchers found that the risk of developing permanent AF was associated with the use of NSAIDs by heart failure patients.[1] In this study the authors concluded that the association was due not to a detrimental effect of the drugs, but rather to the inflammation (a known initiator of AF) and associated pain prompting the use of drugs in the first place. It seems to me that if this hypothesis is indeed true, then one must also conclude that NSAIDs do not eliminate inflammation, but merely mask its symptoms.
[1] De Caterina, R, et al. Long-term use of anti-inflammatory drugs and risk of atrial fibrillation. Archives of Internal Medicine, Vol. 170, No. 16, September 13, 2010, pp. 1450-55