Common NSAIDs and COX-2 pain relievers are under the microscope for increased risk of heart failure, according to a study in the BMJ. And what they find is eye-opening: Some NSAIDs at higher doses double the risk of heart failure.

Previous studies have established a link between overall use of these pain relievers and an increased risk of heart failure, but the risk associated with individual drugs and dosages has been unknown. So researchers set out to do just that.

The study's researchers, led by Giovanni Corrao at the University of Milano-Bicocca in Italy, followed the risk of hospital admission for heart failure with use of individual NSAIDs.

Some examples of COX-2 (a type of NSAID) and NSAIDs are Bextra, Celebrex, diclofenac, and Vioxx, aspirin, ibuprofen (Motrin, Advil), and naproxen (Aleve, Naprosyn).

Their results are based on almost 10 million NSAIDs users from four European countries (the Netherlands, Italy, Germany, and the United Kingdom). They found that while NSAIDs raise the risk of heart failure, that risk was more elevated for some types than others.

Researchers reported that ibuprofen, diclofenac, and naproxen were all associated with increased risk, and that higher doses of ibuprofen and diclofenac doubled the odds, while increased risk with higher dosage of naproxen was slightly lower.

A total of 27 individual NSAIDs, including 23 traditional NSAIDs and four selective COX-2 inhibitors, were included in the analyses. Overall, 92,163 hospital admissions for heart failure were identified and matched with 8,246,403 control patients.

There was no evidence that celecoxib was related to an increased risk of admission for heart failure at commonly used doses. Since the painkiller was used widely used in low doses, the risk of higher doses was unclear.

Since the study was observational only, no firm conclusions could be drawn about cause and effect, and information on absolute risks was not provided.

Corrao and team conclude:  “Our study . . . provides evidence that current use of both COX-2 inhibitors and traditional individual NSAIDs are associated with increased risk of heart failure. Furthermore, the magnitude of the association varies between individual NSAIDs and according to the prescribed dose.

"Because any potential increased risk could have a considerable impact on public health, the risk effect estimates provided by this study may help inform both clinical practices and regulatory activities.”