NSAIDs Linked to Higher Atrial Fibrillation Risk

Pauline Anderson

April 09, 2014

Taking nonsteroidal anti-inflammatory (NSAID) drugs appears to be associated with an increased risk for atrial fibrillation (AF), even after adjustment for ventricular end-diastolic dimension, known to be increased with NSAID use, a new study confirms.

Patients using NSAIDs for 2 to 4 weeks had a 76% higher risk of developing AF compared with those who hadn't taken these pain medications, researchers found.

The results suggest that the increased risk occurs shortly after starting treatment and may resolve over time, said the authors, led by Bouwe P. Krijthe, Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.

The underlying mechanism connecting NSAID use with AF isn't clear and "deserves further attention," the authors conclude.

The study is published online April 8 in BMJ Open.

Resting ECG

AF, a common arrhythmia in the elderly, is associated with stroke, heart failure, increased mortality, and reduced life expectancy. NSAID use has also been associated with myocardial infarction, stroke, and heart failure. Other recent studies have suggested that NSAID use may increase the risk for AF, the researchers note, but most have been retrospective case-control or claims database studies with a limited ability to control for potential confounders, they note.

"Therefore, the objective of this study was to investigate whether use of NSAIDs is associated with AF in a prospective population-based cohort study with precise data on incident AF, complete information on drug use and potential confounders," they write.

Included were 8423 participants from the Rotterdam Study, a well-known population-based prospective cohort study examining risk factors for disease in older adults in the Ommoord district of Rotterdam, The Netherlands. The mean age of the study population was 68.5 years, and most participants (58.6%) were women.

Researchers obtained a resting electrocardiogram (ECG) for participants at baseline and then followed participants with ECG assessments during follow-up visits. They used 3 different methods for gathering and assessing AF cases; they included every clinically recognized case from 2 different sources of medical records and used repeated screening ECG assessments.

The investigators gathered data on NSAID use from collaborating pharmacies and categorized participants into current users (14 or fewer days, 15 to 30 days, and more than 30 days), past users (stopped for 30 or fewer days, 31 to 180 days, or more than 180 days), and never users.

Over a mean follow-up of 12.9 years, 857 participants developed AF. At the time of diagnosis, 261 had never used NSAIDs, 554 had used NSAIDs in the past, and 42 were currently using NSAIDs.

Among current users, 29 used a nonselective NSAID, 5 used a cyclooxygenase (COX)-1 selective NSAID, and 7 used a COX-2 selective NSAID.

Use of an NSAID for 15 to 30 days was associated with an increased risk for AF compared with never use (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.07 - 2.88), adjusted for age, sex, and cardiovascular risk factors, including blood pressure, body mass index, total and high-density lipoprotein cholesterol, and smoking status.

Recent Use

Recent past use of NSAIDs — within the preceding 30 days — was associated with an even higher risk for AF (HR, 1.84; 95% CI, 1.34 - 2.51), adjusted for age, sex, and cardiovascular risk factors.

Although higher dosages (more than 1 prescribed daily dose) seemed to be associated with a higher risk for AF, this association didn't reach statistical significance.

The results suggest that the increased risk occurs shortly after starting a prescription for NSAIDs. According to the authors, this may be because those with symptoms stopped taking the drug.

As for mechanisms linking NSAID use to AF, because these drugs inhibit COX enzymes expressed in the kidneys, such inhibition may lead to fluid retention and increased blood pressure. NSAIDs also increase end-diastolic and end-systolic dimension, and these changes could explain part of the association. Alternatively, because NSAIDs are used as anti-inflammatory drugs, the underlying inflammatory conditions and pain they treat may be associated with AF.

In any case, establishing that underlying mechanism should be a subject of future research, said the authors.

Among the limitations of the study were that it lacked information on the condition being treated with an NSAID and on over-the-counter use of these drugs.

The authors have disclosed no relevant financial relationships.

BMJ Open. Published online April 8, 2014. Abstract

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