Non-aspirin NSAIDs associated with risk for atrial fibrillation or flutter, study finds

Nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase (COX)-2 inhibitors may be associated with increased risk for atrial fibrillation or flutter, according to a new study.

Researchers performed a population-based case-control study of patients in a Danish database to examine the relationship between non-aspirin nonselective NSAIDs (ibuprofen, naproxen, ketoprofen, dexibuprofen, piroxicam, and tolfenamic acid) or selective COX-2 inhibitors and atrial fibrillation or flutter. A total of 32,602 patients who had had a first inpatient or outpatient diagnosis of atrial fibrillation or flutter between 1999 and 2008 (54% men, mean age 75 years) were compared with 325,918 age- and sex-matched controls. The study's main outcome measures were current NSAID use (defined as use at the time of admission) or recent NSAID use (defined as use before admission); current use was further defined as new (first NSAID prescription filled within 60 days before diagnosis) or long-term. The study was published online July 4 by BMJ.

Overall, 2,925 case-patients and 21,871 controls were classified as current users of non-aspirin NSAIDs (9% vs. 7%). When compared with no NSAID use, the incidence rate ratios for the association between current drug use and atrial fibrillation or flutter were 1.33 (95% CI, 1.26 to 1.41) and 1.50 (95% CI, 1.42 to 1.59) for nonselective non-aspirin NSAIDs and COX-2 inhibitors, respectively. After adjustment for age, sex, and risk factors, the incidence rate ratios were 1.17 (95% CI, 1.10 to 1.24) and 1.27 (95% CI, 1.20 to 1.34), respectively, among current users versus 1.46 (9%% CI, 1.33 to 1.62) and 1.71 (95% CI, 1.56 to 1.88), respectively, among new users.

The authors noted that their study did not include data on lifestyle factors such as body size and that their results may have been affected by confounding, among other limitations. Nevertheless, they concluded that use of non-aspirin NSAIDs was associated with an increased risk for atrial fibrillation or flutter, especially among new users, who had a 40% to 70% increase in relative risk. COX-2 inhibitors were associated with a higher risk than nonselective non-aspirin NSAIDs, and elderly patients appeared to be at highest risk. New treatment with COX-2 inhibitors seemed to be associated with higher risk in patients with chronic kidney disease or rheumatoid arthritis (adjusted incidence rate ratios, 2.87 [95% CI, 1.53 to 5.38] and 2.49 [95% CI, 1.40 to 4.42], respectively). The authors wrote that their study “adds evidence that atrial fibrillation or flutter need to be added to the cardiovascular risks under consideration when prescribing NSAIDs.”

The author of an accompanying editorial reiterated the authors' cautions regarding potential confounding and pointed out that the association between NSAID use and atrial fibrillation need not be due to a cause-and-effect relationship. He concluded that clinicians should be cautious in applying the current study's results in clinical practice. “However,” he wrote, “NSAIDs (non-selective NSAIDs and COX-2 inhibitors) should continue to be used very cautiously in older patients with a history of hypertension or heart failure, who are already at high risk for adverse effects of these drugs, regardless of whether an association between NSAIDs and atrial fibrillation actually exists.”