In a newly published study from Denmark, use of non-selective, nonsteroidal anti-inflammatory drugs (NSAIDs) and Cox-2 inhibitors was associated with a significantly increased risk for atrial fibrillation.
Non-selective NSAIDs include the active ingredients in drugs such as Advil, Motrin and Aleve, and Naprosyn. The prescription drug Celebrex is a Cox-2 inhibitor. The researchers also included older Cox-2 inhibitor drugs such as diclofenac (Voltaren), etodolac (Lodine), and meloxicam (Mobic).
The risk was highest for new users of the drugs. New NSAID users had a 46% increase in risk, and new Cox-2 inhibitor users had a 71% increase in risk compared to people who did not take the pain relievers.
WebMD contacted Pfizer -- the maker of Advil, Celebrex, and the non-selective NSAID Feldene -- for comment. Jimison MacKay, a spokesman for Pfizer, says the study "does not change Pfizer’s understanding of the benefit-risk profile of NSAIDs, an important treatment option for appropriate patients."
"Pfizer recognizes the importance of research that has the potential to advance therapy and improve the lives of patients," MacKay says. "This retrospective observational analysis has a number of limitations that are acknowledged in the manuscript. Further studies and preferably randomized clinical trials are warranted to establish the cardiovascular profile of NSAIDs."
NSAIDs and Heart Flutter
Atrial fibrillation risk increases with age, with close to one in 10 people over the age of 80 affected by the condition.
Recent studies have linked regular use of NSAIDs, including Cox-2 inhibitor pain relievers, to an increased risk for other heart conditions in both heart patients and older people without cardiovascular disease.
But the Danish study, published July 4 in the journal BMJ, is among the first to suggest an association with atrial fibrillation or flutter, which affects around 2 million Americans.
The study included just over 32,500 Danish patients diagnosed with atrial fibrillation or flutter between 1999 and 2008. Each case was compared with 10 patients who did not have the heart condition.
The participants were classified as current or recent non-selective NSAID or Cox-2 inhibitor users. Current users were further classified as new users or long-term users.
Researchers estimated that about four additional cases of atrial fibrillation per year could be expected among 1,000 new users of non-selective NSAIDs and seven extra cases of the heart condition could be expected among new Cox-2 inhibitor users.
But researcher Morten Schmidt, of Denmark's Aarhus University Hospital, says the observational design of the study limits the conclusions that can be drawn.
"Although our findings were robust, they do not prove that these pain relievers caused the atrial fibrillation," he tells WebMD. "It may be that differences between users and non-users of these drugs influenced the findings."
University of Massachusetts Medical School professor of medicine Jerry H. Gurwitz, MD, tells WebMD the study is "hypothesis generating."
"We don't have enough evidence at this time to indicate whether this is cause and effect," he says. "And if this association does exist, it is not really clear if it would make a clinical difference because we have a pretty clear idea when these drugs should be used cautiously or not at all."
Gurwitz explains that non-selective NSAIDs and Cox-2 inhibitors should not be used by patients with heart failure or kidney failure, and they should be used with extreme caution by older patients with other heart conditions.