Ibuprofen-like painkillers linked to an increased risk of heart failure

"Ibuprofen could raise the risk of heart failure by up to 83%," claims the Daily Mirror. But this headline massively overstates the danger of this painkiller.

In fact, new research suggests that taking painkillers known as non-steroidal anti-inflammatory drugs (NSAIDs) – which includes ibuprofen – increases the risk of heart failure by less than 20% overall.

NSAIDs are a group of painkilling medicines commonly taken by people with joint problems, backache and arthritis. They are prescribed to relieve pain and reduce inflammation.

The study found that the risk of heart failure varies between NSAIDs and according to dosage.

While a rarely prescribed NSAID called ketorolac almost doubled the risk of heart problems, the more commonly taken ibuprofen increased the chance of heart problems by just 18%.

The risk was also highest for people who took an NSAID on a daily basis and in very high doses.

Some NSAIDs, such as ketoprofen and celecoxib, did not seem to increase the risk at all at usual doses.

This latest study backs up previous evidence that NSAIDs are clearly linked with an increased risk of heart failure. But it's important to bear in mind that the risk is, for most people, still very small.

Heart failure is caused by a wide range of conditions, including high blood pressure, heart attacks and obesity.

Where did the story come from?

This was a large study involving more than 7 million people. It was carried out by researchers from seven European institutions, led by the University of Milan, and was funded by the European Union. The study was published in the peer-reviewed British Medical Journal (BMJ).

Some UK media outlets failed to make it clear the study was carried out among people who were taking prescribed NSAIDs, usually for a long-term condition such as backache or arthritis, rather than people taking the occasional over-the-counter painkiller.

The Daily Express headline wrongly says: "Over-the-counter painkillers raise risk by almost 20%," although at least they used the more credible 20% relative risk figure.

The Daily Mirror's scaremongering headline stating an increased risk of heart failure of 83% was way above that of most of the NSAIDs studied and was wrongly linked to ibuprofen.

BBC News took a more balanced view, and included interviews with experts who discussed exactly who is and isn't at risk from NSAIDs and heart failure.

What kind of research was this?

This was a so-called nested case-control study, which used drug databases to identify people who'd been prescribed NSAIDs during a 10 year period. Of these, those who had been admitted to hospital for heart failure were compared with others in the database of the same age and sex.

This type of study helps researchers identify links between individual drugs and outcomes such as heart disease. They don't directly prove the drug causes the heart disease, but we've already seen randomised controlled trials showing NSAIDs in general do seem to raise the chances of heart failure.

What did the research involve?

Researchers used five drug databases from four European countries to identify adults who'd had at least one NSAID prescription between 2000 and 2010. They then identified anyone from that group who'd later been admitted to hospital with heart failure and matched them with up to 100 "controls" – people the same age and sex, who'd started the study around the same time.

They then looked to see whether a current prescription of an NSAID (within the last 14 days) affected someone's chances of being admitted to hospital with heart failure.

The databases were from the UK, Italy, the Netherlands and Germany. For the UK and the Netherlands, the databases also recorded the daily dose prescribed, so the researchers used this information to calculate the effect of low, normal, high or very high prescribed doses.

The researchers corrected their figures to take account of factors such as previous diagnosis of heart failure or other medical condition and other medicines being taken.

What were the basic results?

The study found 92,163 people who'd been admitted to hospital with heart failure among the 7.6 million people prescribed an NSAID who were included in the study. People admitted with heart failure tended to be older, with an average age of 77, and many of them also had high blood pressure, high cholesterol, cardiovascular disease or diabetes.

Compared to others of about the same age and sex, those who'd been admitted for heart failure were more likely to be currently taking a prescribed NSAID.

In fact, nearly one in five (17.4 %) of heart failure patients and one in seven (14.4 %) of the matched control groups had a current prescription. This meant that having a current prescription for any NSAID raised the risk of heart failure admission by almost 20% (odds ratio (OR) 1.19, 95% confidence interval (CI) 1.17 to 1.22).

However, more interesting was the information about individual drugs. Nine NSAIDs had a raised risk of heart failure: ketorolac, etoricoxib, indomethacin, rofecoxib, piroxicam, diclofenac, nimeluside, ibuprofen and naproxen.

The degree of increased relative risk varied between them, from ketorolac at 83% to naproxen at 16%.

Some of the NSAIDs, including the commonly used ketoprofen and celeocoxib, did not show any increased risk.

The risk was highest for people taking very high daily doses (twice the usual daily dose) of NSAIDs.

How did the researchers interpret the results?

The researchers said their study results showed that the risk of heart failure in people taking NSAIDs "appears to vary between individual NSAIDs, and is dose dependent". 

They say their findings "might apply to NSAIDs obtained over the counter", although they only looked at prescription drugs.

"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," they observe, adding "they may be inappropriately over-used".

They call for research into the safety of over-the-counter NSAIDs "under the conditions they are typically used".

Conclusion

This useful and well-conducted study isn't the first to say NSAIDs may raise the risk of heart failure. We've known for some time that NSAIDs can have side effects, especially when used at high doses and for long periods.

What this study does help show is the different levels of risk between different NSAIDs, and confirms that the risk depends partly on the dose. It's important to remember that the study only included people who were prescribed NSAIDs and not people who'd bought them over the counter.

The information is most useful to older people taking prescribed NSAIDs long-term for conditions such as gout or arthritis. These are the people most likely to be affected by heart problems linked to NSAIDs.

The study shows that some NSAIDs are less risky than others, and doctors can use this information to discuss with patients which is the most suitable drug if they need long-term anti-inflammatory painkillers.

For people who take NSAIDs over the counter, it's a reminder that these drugs are not risk-free. While an otherwise healtlhy 20-something taking ibuprofen for a day or two to get over backache is highly unlikely to get heart failure as a result, long-term use of NSAIDs at high doses can cause problems.

Sensible advice is to take the lowest dose that works for the shortest period you need it. If you find you need to take NSAIDs very often, or you're taking doses higher than those recommended, you should talk to your doctor about your pain.

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