EXPERT REACTION: Painkillers a heart risk from the start

Embargoed until: Publicly released:

Taking any dose of common non-steroidal anti-inflammatory drugs (NSAIDs), such as naproxen and ibuprofen, for as little as one week has been linked an increased risk of heart attack, according to Canadian research. While the link has been known for some time - the timing of the risk and the impact of dose had remained a question. Now researchers have shown that the risk of heart attack was greatest with higher doses and during the first month of use. The study found that all NSAIDs, including over-the-counter ones such as naproxen, were linked with an increased risk of heart attack. The researchers suggest that people should consider weighing the risks and benefits of NSAIDs before beginning treatment, particularly for higher doses.

Journal/conference: The BMJ

Organisation/s: University of Montreal Hospital Research Center, Canada

Funder: This study is part of MB’s doctoral research thesis in epidemiology. MB received grants from the McGill University Health Centre Research Institute during the conduct of the study.

Media Release

From: The BMJ

Heightened risk of heart attacks found with common painkillers in routine use

Study finds that higher risk of heart attack with common painkillers depends on dose and arises early

Doctors and patients urged to weigh the risks and benefits of ibuprofen, diclofenac, celecoxib, and naproxen

People who use commonly prescribed non-steroidal anti-inflammatory drugs (NSAIDs) to treat pain and inflammation could be raising their risk of having a heart attack, as early as in the first week of use and especially within the first month of taking high doses of such medication, suggests a study in The BMJ this week.

Previous studies suggested that both traditional and COX 2 selective NSAIDs could increase the risk of acute myocardial infarction (heart attack), but the timing of the risk, the effect of dose, treatment duration, and the comparative risks between NSAIDs were poorly understood.

An international team of researchers led by Michèle Bally of the University of Montreal Hospital Research Center (CRCHUM), then an epidemiology doctoral student at McGill University in Canada, set out to characterise the risks of heart attack associated with use of oral NSAIDs under real life practice circumstances.

For their study, the researchers carried out a systematic review and a meta-analysis of relevant studies from various healthcare databases including those from Canada, Finland and the United Kingdom.

Collectively, they analysed results on 446,763 people of whom 61,460 had a heart attack.

The NSAIDs of interest to the researchers were celecoxib, the three main traditional NSAIDs (diclofenac, ibuprofen, and naproxen), and rofecoxib. To provide guidance, the researchers presented their results as probabilities of having a heart attack. They looked at various scenarios corresponding to how people might routinely use these drugs.

The study found that taking any dose of NSAIDs for one week, one month, or more than a month was associated with an increased risk of heart attack. Naproxen was associated with the same risk of heart attack as that documented for other NSAIDs. With celecoxib, the risk was lower than for rofecoxib (Vioxx) and was comparable to that of traditional NSAIDs.

Overall the increase in risk of a heart attack is about 20 to 50% if using NSAIDs compared with not using these medications. To put this in perspective, as a result of this increase, the risk of heart attack due to NSAIDs is on average about 1% annually. The type of analysis the researchers used allowed them to conclude with greater than 90% probability that all NSAIDs studied are associated with a heightened risk of heart attack.

Further analysis suggested that the risk of heart attack associated with NSAID use was greatest with higher doses and during the first month of use. With longer treatment duration, risk did not seem to continue to increase but the researchers caution that they did not study repeat heart attacks such that it remains prudent to use NSAIDs for as short time as possible.

This is an observational study based on drug prescribing or dispensing and not all potentially influential factors could be taken into account.

Although this means that conclusions cannot be made about cause and effect, the authors say that their study was the largest investigation of its type and that its real-world origin helped to ensure that findings were broadly generalisable.

The researchers also emphasise the advantages of sharing ‘de-identifed’ patient data as this helps making healthcare decisions that may improve patient care.

They conclude: “Given that the onset of risk of acute myocardial infarction 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.”

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Expert Reaction

These comments have been collated by the Science Media Centre to provide a variety of expert perspectives and reflect independent opinion on this issue. Feel free to use these quotes in your stories. Views expressed are the personal opinions of the experts named. They do not represent the views of the SMC or any other organisation unless specifically stated.

Professor Greg Dusting is a researcher at the Centre for Eye Research Australia and a professorial fellow at the University of Melbourne

This is clearly a very important issue given both its publication in BMJ and more importantly that millions of patients (and self medicated people) around the world are currently on these NSAIDS for inflammatory disease. I worked on the original mechanisms of action of NSAIDs, and why they are potentially dangerous in SOME patients, an area that led to a Nobel Prize on these drugs for my mentor- the late Sir John Vane in UK.

There is basic science evidence that could suggest that these drugs, many of which are freely available as over the counter medications even in supermarkets, could present a problem in some patients with concurrent cardiac risk factors, but the clinical and epidemiological evidence is crucial here (about the pharmacological type of NSAID, the dose and duration of treatment or NSAID consumption, as well as the medical status of the subjects in which the trials have been done).

Basically the decision is a trade-off for the physician about whether the pain relief that these powerful drugs provide for arthritis is worth the very slightly increased risk of a cardiovascular event for each particular patient.

Last updated: 10 May 2017 11:13am
Emeritus Professor Mark Wahlqvist is former Professor and Head of Medicine at Prince Henry’s Hospital and Monash Medical Centre, Associate Dean (International Health and Development) and Director of the Asia Pacific Health and Nutrition Centre

Seen in a broader context, these findings signal an imperative to seek wellbeing, health and longevity from low risk anti-inflammatory options such as regular movement in public open space and dietary diversity. Research has shown just how extensive and complimentary the anti-inflammatory properties of diverse foods are and their use offers a high benefit to risk ratio. They are affordable and can be provided sustainably.

Last updated: 09 May 2017 3:45pm
Professor John McNeil AM

These results add to a series of previous studies suggesting that NSAIDS increase the risk of myocardial infarction. However, these drugs can provide substantial relief to many patients with various types of pain and the trade off against a relatively small risk of heart disease may well be worth taking. The longstanding advice to take the lowest effective dose for the shortest time is sound, especially in those whose risk of heart disease is already high. There was no substantial difference in risk between any of the commonly used NSAIDS.

Last updated: 09 May 2017 3:42pm

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