NSAID Use Increases Irregular Heartbeat Risk

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Study results show older patients who use ibuprofen and other prescription and over-the-counter NSAIDs are at increased risk for atrial fibrillation.

A new prospective study published in BMJ Open found that a month’s steady use of prescription non-steroidal anti-inflammatory drugs (NSAIDs) increases the risk of atrial fibrillation (AF) among elderly patients by around 80%.

Researchers in The Netherlands tracked data from 8,400 people over an average of 13 years. At baseline, the sample population was mostly female (58%), mostly senior (average age, 68.5 years), and entirely free of AF.

Of the 857 who developed AF, 261 had never used NSAIDs, 554 had used them in the past, and 42 were currently taking the medication.

Analysis of those numbers (adjusted for age, sex, and several potential confounders), showed current use of NSAIDs was strongly associated with increased risk compared with never-use (HR 1.76, 95% CI 1.07 to 2.88).

Recent use (that which had been discontinued within the past 30 days) was associated even more strongly with increased risk when compared to never-use (HR 1.84, 95% CI 1.34 to 2.51). Once patients had stopped for more than 30 days, however, the risk appeared to drop quickly back down toward normal.

Other studies, many of them retrospective, have found links between NSAIDs and atrial fibrillation, but the authors of the current study reported several particular strengths of their design beyond its prospective nature.

“We included follow-up data from the Rotterdam Study, which is based in the general population and contains detailed information on drug exposure. Compared with previous database studies, we were able to use more detailed information for a range of potential confounders and to adjust for established risk factors of atrial fibrillation such as blood pressure and body mass index, and in a subsample for echocardiographic measures,” they wrote.

“Also, we were able to use a more detailed clinical assessment of atrial fibrillation. We used 3 different methods for case gathering and assessment, as we included every clinically recognized case from two different sources of medical records. In addition, we included repeated screening ECG assessments of the study population.”

Several previous studies have found a positive correlation between NSAID dosage and AF risk, a finding the new study tended to support. The risk of AF was lower for users of low-dosage NSAIDs (HR 0.97; 95% CI 0.65 to 1.46) than for high-dosage users (HR 1.27; 95% CI 0.80 to 2.03).

The study also tended to confirm earlier findings that COX-2 inhibitors correlate with greater risk of AF than other types of NSAIDS. Among current users who developed AF during the study, the majority (n=29) used a non-selective NSAID, 5 used a COX-1 selective NSAID, and 7 used a COX-2 selective NSAID.

That said neither finding on dosage strength on NSAID type was strong enough to reach statistical significance.

Whatever the strengths of the study, the authors stressed the need for additional research to explain the link between NSAID use and AF. They also identified a pair of potential weak spots in their own work.

“Compared with the previously published studies, however, our sample size was smaller. This might explain why some of our estimations did not reach statistical significance,” they wrote. Also, “Our study may have missed over-the-counter use of NSAIDs.”

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Kelley Branch, MD, MSc | Credit: University of Washington Medicine
Kelley Branch, MD, MS | Credit: University of Washington Medicine
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