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Study reinforces link between NSAIDs and COX 2s and risk of heart failure

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Commonly used prescribed painkillers for treating pain and inflammation are associated with an increased risk of hospital admission for heart failure, which varies depending on the drug in question and the dose at which it is prescribed, according to international researchers.

The drugs in question include both traditional non-steroidal anti-inflammatory drugs, such as ibuprofen, and new generation anti-inflammatory drugs like COX 2 inhibitors.

“She risk seems to vary between drugs and according to the dose”

Study authors

Previous studies have suggested a link between NSAIDs and COX 2s and increased heart failure risk, but the risk and dose-response associated with individual drugs was largely unknown until now.

New research, led by the University of Milano-Bicocca and published in the British Medical Journal, has revealed the estimated risk of hospital admission for heart failure with use of individual NSAIDs.

The findings are based on almost 10 million patients using painkillers from across the Netherlands, Italy, Germany, and the UK.

A total of 27 individual NSAIDs, including 23 traditional NSAIDs and four selective COX 2 inhibitors, were included in the observational study.

Overall, 92,163 hospital admissions for heart failure were identified and matched with 8,246,403 control patients.

The researchers found that current use of any NSAID was associated with a raised risk of admission for heart failure, compared with past use.

“This large observational study reinforces previous research”

Peter Weissberg

Admission risk for heart failure increased for seven NSAIDs – diclofenac, ibuprofen, indomethacin, ketorolac, naproxen, nimesulide and piroxicam – and two COX 2s – etoricoxib and rofecoxib.

In addition, the researchers said they found that the magnitude of risk varied between individual NSAIDs and according to the dose prescribed.

At very high doses, risk of admission for heart failure doubled for some NSAIDs, including diclofenac, etoricoxib, indomethacin, piroxicam and rofecoxib

Even medium doses of indomethacin and etoricoxib were associated with increased risk, they said.

However, they found no evidence that the COX 2 celecoxib was related to an increased risk of admission for heart failure at commonly used doses.

But the researchers cautioned that celecoxib was used mostly in low doses, so its safety at higher remained unexplored.

The study authors said their findings offered “further evidence that the most frequently used individual traditional NSAIDs and selective COX 2 inhibitors are associated with an increased risk of hospital admission for heart failure”.

“Moreover, the risk seems to vary between drugs and according to the dose,” they highlighted.

They added: “The risk effect estimates provided by this study may help inform both clinical practices and regulatory activities.”

Commenting on the research, two Danish cardiology experts stated that, owing to the widespread use of NSAIDs, “even a small increase in cardiovascular risk is a concern for public health”.

British Heart Foundation

Professor Peter Weissberg

Peter Weissberg

In a linked editorial in the BMJ, they argued that “requirements for healthcare professionals providing advice on their use and potential harm is warranted”.

Professor Peter Weissberg, medical director at the British Herat Foundation, said the study “reinforces” previous findings that some NSAIDs increased the risk of developing heart failure.

“It has been known for some years now that such drugs need to be used with caution in patients with, or at high risk of, heart disease. This applies mostly to those who take them on a daily basis rather than only occasionally,” he said.

He added that, as heart and joint problems often coexist, particularly in the elderly, the study “serves as a reminder” to clinicians to “consider carefully how they prescribe NSAIDs”.

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