Researchers looked at data from 446,763 people and found some evidence that all commonly-used non-steroidal anti-inflammatory drugs (NSAIDs) like Ibuprofen 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.
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.
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.
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.
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.
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]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.
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).
Links to the headlines
Daily Mail, May 10 2017
The Guardian, May 9 2017
BBC News, May 10 2017
Sky News, May 10 2017
The Daily Telegraph, May 9 2017
Daily Mirror, May 10 2017
The Sun, May 10 2017