Ibuprofen linked to increased risk of heart attacks
"Taking painkillers for just one week 'raises the risk of a heart attack'," the Daily Mail reports. The report is based on a new analysis that found a link between anti-inflammatory painkillers like ibuprofen and heart attack risk.
Researchers looked at data from 446,763 people and found some evidence that all commonly-used non-steroidal anti-inflammatory drugs (NSAIDs) appear to increase the risk of heart attack, and that the risk rises in the first week of use. The study found the risk was highest with higher doses.
However, the study does leave some unanswered questions. Researchers only looked at effects among those prescribed the drugs and not those using over the counter, so they may not be representative of the general population.
And while the study tells us how likely people taking an NSAID are to have a heart attack, compared to people who hadn't used them in the past year, it doesn't give an indication of what the actual baseline risk of a heart attack is in these groups. And this risk varies from person to person.
It also can't prove NSAIDs were the direct cause of heart attack – it didn't take into account all possible influencing factors, such as smoking for example. Also, not all results reached statistical significance and so could have been the result of chance.
If you've been prescribed NSAIDs and are concerned about your heart attack risk, speak to your GP. When treating minor ailments with painkillers, always use the lowest effective dose for the shortest time possible.
Where did the story come from?
The study was carried out by researchers from McGill University and the Centre Hospitalier de l'Université de Montreal, both in Canada, Hospital District of Helsinki in Finland, and Leibniz Institute for Prevention Research and Epidemiology in Germany. It was funded by McGill University.
The study was published in the peer-reviewed British Medical Journal (BMJ) on an open access basis, meaning it is free to read online.
The study was widely covered in the UK media and the majority of the coverage was of a good quality. The Mail, The Daily Telegraph, Sky News, BBC News and The Mirror all carried balanced and accurate reports.
The headline in The Guardian – "Common painkillers may raise risk of heart attack by 100%" – is misleading because the 100% increased risk figure relates to high dose rofecoxib, which is far from being a common painkiller, having been unavailable for 13 years. Also, the 100% figure relates to the upper end of the estimated range of risk.
The Sun's headline – "Taking ibuprofen to treat pain 'for just ONE DAY increases your risk of heart attack by half'," – also overstates the risk, as the figure is for ibuprofen use between one and seven days, not one day only.
What kind of research was this?
This is a meta-analysis, using individual patient data taken from large observational studies. A meta-analysis is a good way to pool data from previous research, and using individual patient data helps balance risks and avoid bias. However, observational studies cannot prove cause and effect, because confounding factors other than the ones measured may be influencing the results.
What did the research involve?
Researchers looked for observational studies based on big patient databases that investigated non-steroidal anti-inflammatory drugs (NSAID) use and heart attack. The studies compared people who'd had a heart attack with those who had not, and used prescribing data to see whether they had been prescribed NSAIDs.
The researchers analysed this data, taking account of a wide range of potential confounding factors. They calculated the risk of having a heart attack after being prescribed each of the five NSAIDs, at different time periods, and different doses.
The methods used were robust and the results from the different studies were similar, which suggests the findings are likely to apply across populations with different baseline risks of heart attack. After excluding inappropriate studies, the researchers asked for access to individual patient data to carry out their analysis. Four studies refused access, leaving them with data from four other studies – two from Canada, one from Finland and one from the UK.
What were the basic results?
The study found mixed results. Recent and current use of any NSAID is linked to a raised risk of having a heart attack, compared to someone who has not used an NSAID in the past year. However, some of these results did not reach statistically significant thresholds – meaning it's possible that risk wasn't increased in these cases. That said, the figures were all in the same direction – tending towards showing an increase in risk.
The raised risk was generally increased with use in the previous year or month, starting in the first week of being prescribed the drugs in the study period. It seemed highest between eight to 30 days – i.e. the first month of taking the drug. Although the risk was still raised after a month, it tailed off. There was some variation in this trend though – some NSAIDs had a higher risk after 30 days and some a lower risk.
The increased risk of heart attack for any dose of NSAIDs in the first week of use, compared to no use in the past year, was:
- Diclofenac – a 50% increased risk (odds ratio [OR] 1.50, 95% credible interval [CrI] 1.06 to 2.04) (credible intervals are similar to confidence intervals, but are generated by a specific kind of statistical analysis called Bayesian analysis)
- Ibuprofen – a 48% increased risk (OR 1.48, 95% CrI 1.00 to 2.26]
- Naproxen – a 53% increased risk (OR 1.53, 95% CrI 1.07 to 2.33)
- Rofecoxib (a drug that has been withdrawn) – a 58% increased risk (OR 1.58, 95% CrI 1.07 to 2.17)
Higher doses (more than 1,200mg a day for ibuprofen, more than 750mg a day for naproxen and more than 25mg a day for rofecoxib) further increased the risk.
Previous studies had found a lower heart attack risk for naproxen than with other NSAIDs, but that was not apparent in this study.
How did the researchers interpret the results?
The researchers said their study was "the largest of its type," with "broadly generalizable" findings which showed "current use of all studied NSAIDs, including naproxen, was associated with an increased risk of acute myocardial infarction [heart attack]."
They add: "Given that the onset of risk … occurred in the first week and appeared greatest in the first month of treatment with higher doses, prescribers should consider weighing the risks and benefits of NSAIDs before instituting treatment, particularly for higher doses."
Conclusion
This study is a useful addition to our knowledge about the links between NSAIDs and heart attack risk. The study suggests all commonly-used NSAIDs are linked to a similarly-raised risk of heart attacks, that the risk generally rises with the dose, and that it is highest in the first month of treatment.
The researchers did a good job at taking account of potential confounding factors that could have affected the results. Even so, we don't know for sure that the NSAIDs were the direct cause of the problem. For example, if you are prescribed NSAIDs for a painful condition, and have a heart attack two weeks later, it's hard to know whether the cause was the NSAID or the condition itself. They were also not able to take into account some known risk factors for heart attacks such as smoking and body mass index (BMI).
The study doesn't tell us about our own individual risk of heart attack, which is important when thinking about how you might be affected by NSAIDs. If your risk of having a heart attack in the next 10 years is high – say 30% – then a 48% increased chance of heart attack takes it up to just under 45%.
But if you have a low risk of having a heart attack – say 1% – then a 48% increase only takes the risk up to 1.48%. An increase in risk may be statistically significant, but have little clinical significance.
The study findings back up current advice that doctors should consider people's heart attack risk before prescribing courses of NSAIDs, particularly at higher doses.
The research was carried out using data on prescription NSAIDs, so it didn't look specifically at occasional use of over the counter ibuprofen. However, as with all drugs it makes sense only to use them when you need them, and to take the lowest dose that works, for the shortest period of time that you need it.
If you often use painkillers, it may be a good idea to talk to your doctor to see whether there's an underlying problem that needs treating, or ask about alternatives to painkillers, such as physiotherapy.
Read more about treatment options for pain.
