Non-steroidal anti-inflammatory drugs (NSAIDs) can increase the risk of heart attack within the first week of use, according to results from a study of nearly 450,000 people.
Analysing data from 446,763 people in Canada and Europe, 61,460 of whom had a heart attack, researchers found that the greatest increase in risk of heart attack occurred in the first month of taking high doses of NSAIDs.
Reporting their results in the British Medical Journal
(online, 3 May 2017), the Canadian researchers say that while the increased risk of a heart attack with NSAIDs has been shown in other studies, the effect of factors such as short-term or intermittent use, dosage and type of NSAID have not been understood previously.
The analysis, which included ‘real-life’ data from several studies including one from the UK General Practice Research Database, found that celecoxib, diclofenac, ibuprofen, naproxen and rofecoxib all increased the risk of heart attack whether taken for one week, one month, or longer than a month, compared with not using these medications.
Comparisons between the different NSAIDs showed that the risk of heart attack with rofecoxib was greater than that seen in the other drugs in the class, which the researchers said could explain why the link with heart attack was first noted in rofecoxib trials, before the drug was withdrawn in 2004.
Compared with non-use, the associated increased risk of a heart attack when taking NSAIDs was 20%–50%, rising to 75% for ibuprofen and naproxen and more than 100% for rofecoxib.
While the increased risk of heart attack became apparent in the first week of treatment, the greatest risk was seen when patients had been treated for 8–30 days at a high daily dose for ibuprofen (>1,200 mg), naproxen (>750 mg) and rofecoxib (>25 mg).
Naproxen was found to carry a similar risk of heart attack as other traditional NSAIDs, ibuprofen and diclofenac, as did the newer COX-2 inhibitor, celecoxib.
There were no obvious further increases in risk beyond the first 30 days, the results show, although the researchers admit they did not look at repeat heart attacks.
The researchers conclude that their data, which came from various scenarios of actual use, could help prescribers compare the risk of heart attack of NSAID dose levels and treatment durations.
Lead author MichÃ¨le Bally, epidemiologist and researcher at the University of Montreal, says that prescribers should weigh up the risks and benefits of NSAID use before starting treatment, particularly for the highest doses. “When making a choice to treat occasional pain, fever, or inflammation people may want to consider all available treatment alternatives as the increased risk of heart attack associated with NSAIDs may begin in the first seven days of treatment,” she says.
“People taking these drugs for a chronic painful condition may want to consider whether the benefit of increasing the dose for better relief outweighs a possible increased risk of heart attack.”
Bally adds that people who already have heart disease or cardiac risk factors will be most at risk because their baseline risk of a heart attack is higher.
Commenting on the study, Mike Knapton, associate medical director at UK charity the British Heart Foundation, agrees that patients and doctors must weigh up the risks and benefits of taking high doses of NSAIDs, particularly in those with an already increased risk. “This large-scale study worryingly highlights just how quickly you become at risk of having a heart attack after starting NSAIDs.
“Whether you are being prescribed painkillers like ibuprofen, or buying them over the counter, people must be made aware of the risk and alternative medication should be considered where appropriate,” he adds.
Helen Stokes-Lampard, chair of the Royal College of GPs, says that it is important that the results of this study, and others, are taken on board to inform clinical guidelines and patients themselves, but says that in general, fewer NSAIDs are now being used by GPs to treat chronic pain.
“The use of NSAIDs in general practice to treat patients with chronic pain is reducing and some of the drugs in this study are no longer routinely prescribed in the UK, such as coxibs, as we know that long-term use can lead to serious side effects for some patients,” she says.
“But these drugs can be effective in providing short-term pain relief for some patients – what is important is that any decision to prescribe is based on a patient’s individual circumstances and medical history, and is regularly reviewed.
“It is vital that GPs have adequate access to a variety of therapies in the community, so that we can develop a treatment plan for our patients living with chronic pain that works best for them,” she adds.
 Bally M, Dendukuri N, Rich B et al. Risk of acute myocardial infarction with NSAIDs in real world use: bayesian meta-analysis of individual patient data. BMJ 2017;357:j1909. doi: 10.1136/bmj.j1909