Commonly prescribed anti-inflammatory painkillers, including ibuprofen, raise the risk of hospital admission for heart failure, a large European study suggests.
The drugs — typically given to relieve pain and fever — include traditional non-steroidal anti-inflammatory drugs (NSAIDS) and newer generation anti-inflammatory drugs, known as COX-2 inhibitors.
Several previous studies have linked use of NSAIDs with increased risk of heart failure. Now researchers, led by Giovanni Corrao at the University of Milano-Bicocca in Italy, have explored the risk of individual NSAIDs at various doses.
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More than 92,000 hospital admissions for heart failure in Italy, the Netherlands, Germany and the United Kingdom were identified and compared with 8.2 million controls of the same age and sex. Of these, 17 per cent of the heart failure cases and 14 per cent of the controls were current users of NSAIDS
Use of seven traditional NSAIDs — including ibuprofen, diclofenac and naproxen — were associated with increased risk of hospital admission for heart failure, as were two COX-2 inhibitors: etoricoxib and rofecoxib.
"Our study, based on real world data on almost 10 million NSAIDs users from four European countries, provides evidence that current use of both COX-2 inhibitors and traditional individual NSAIDs are associated with increased risk of heart failure," the researchers wrote in Wednesday's edition of the BMJ.
The findings might apply to NSAIDs purchased over the counter as well, they said.
The other NSAIDs associated with a higher risk of heart failure were indomethacin, ketorolac, nimesulide and piroxicam.
Public health consequences
"Although over-the-counter NSAIDs are probably typically used at lower doses, by younger people, and for shorter durations than prescribed NSAIDs, they are sometimes available at the same doses than those prescribed and may be inappropriately overused," the researchers said, calling for further study of the over-the-counter products.
"Therefore, our findings could have large scale consequences in public health."
The degree of association varied between individual NSAIDs. The higher the prescribed dose of the NSAIDs, the higher the heart failure risk. No firm conclusions about cause and effect can be drawn from the observational study.
The study focused on long-term use of NSAIDs by people with an average age of 77 years to treat conditions such as arthritis.
A previous review suggested the risk of hospital admission for heart failure was roughly doubled by all of the NSAIDs studied when compared with placebo.
NSAIDs work to block enzymes that could trigger signs and symptoms of heart failure, especially in susceptible patients, an earlier study suggests.
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In an editorial titled, "NSAIDs and the failing heart," one cardiologist said the clinical perspective of the study was limited because it did not provide data on excess absolute risk.
Physiotherapy and exercise, and other pain treatments, such as acetaminophen or a weak opiate, are other options.
"The selective COX-2 inhibitors and diclofenac have repeatedly been associated with higher cardiovascular risk, and therefore it seems prudent to avoid them and consider lower risk naproxen at the lowest effective dose," wrote Gunnar Gislason, of the cardiology department at Copenhagen University Hospital.
The European Medicines Agency and the U.S. Food and Drug Administration have issued warnings about the potential harmful effects of NSAIDs and diclofenac in particular.
NSAIDs are still widely available over-the-counter in supermarkets and convenience stores.
"This practice further fuels the common misconception that NSAIDs are harmless drugs that are safe for everyone," Gislason said. "Therefore, a more restricted policy by regulatory authorities on the availability of NSAIDs and requirements for healthcare professionals providing advice on their use and potential harm is warranted."