Ibuprofen And Diclofenac May Heighten Cardiac Arrest Risk

Researchers have found an association between cardiac arrest and ibuprofen use, as well as another type of non-steroidal anti-inflammatory drug (NSAID) called diclofenac. A cardiac arrest is a serious emergency where the heart stops pumping blood around the body.

The Danish study looked at 29,000 people who experienced a cardiac arrest, and then at whether these people had taken NSAIDs.

The researchers found the risk of a cardiac arrest was increased by a third for those who took ibuprofen in the 30 days leading up to cardiac arrest. The risk was doubled for those taking diclofenac, which is only available on prescription in the UK. There was no evidence of an increased risk for other NSAIDs.

Pre-existing Conditions?

The underlying biological reasons for this link were not discussed in the study, so it’s not clear what might cause this increased risk of cardiac arrest. It is possible some people were taking NSAIDs because they had symptoms of a pre-existing (possibly undiagnosed) condition that could increase the risk of cardiac arrest, such as heart disease.

An alternative painkiller to try is paracetamol, or you could try physiotherapy for things like joint and muscle pain. Get advice from your pharmacist or GP on the most suitable treatment for your symptoms.

The study was carried out by researchers from institutions in Denmark, including Copenhagen University Hospital, Aalborg University and the University of Southern Denmark. Funding was provided by the European Regional Development Fund, the Novo Nordisk Foundation, and TrygFonden, a foundation that promotes public health.

Case Time Control Study

This observational case-time-control study looked at data from the Danish nationwide registries to find out if there’s a link between using NSAIDs and an increased risk of having a cardiac arrest outside of hospital.

A cardiac arrest is when the heart suddenly stops pumping blood around the body. The person will usually fall unconscious and stop breathing. It’s not the same as a heart attack, although a heart attack can lead to cardiac arrest.

A case-time-control study is good because the same individual is both the case and the control in two different periods of time. This means confounding variables like pre-existing illnesses remain the same when comparing the two groups.

NSAID exposure was assessed by looking at prescribing patterns for the most commonly used NSAIDs in Denmark. These were diclofenac, naproxen and ibuprofen, as well as two COX-2 selective inhibitors, rofecoxib and celecoxib.

The researchers only included people in the analysis who requested a prescription in the case period, but not during the control period. Information on other existing illnesses was obtained from discharge diagnoses from hospital admissions up to five years before the cardiac arrest.

One problem is that prescribing patterns change over time in the general population, but the study accounted for this by using a control group from the general population to adjust for these changes.

Results

The analysis identified 28,947 people who experienced an out-of-hospital cardiac arrest between 2001 and 2010. In the case period, 3,376 people had been treated with an NSAID in the 30 days leading up to cardiac arrest.

Ibuprofen was the most commonly prescribed NSAID, accounting for 51% of total NSAID use, followed by diclofenac, which accounted for 21.8% of total use.

The main findings were:

  • use of any NSAID increased risk of cardiac arrest by 31% (odds ratio [OR] 1.31, 95% confidence interval [CI] 1.17 to 1.46)
  • use of ibuprofen increased risk of cardiac arrest by 31% (OR 1.31, 95% CI 1.14 to 1.51)
  • use of diclofenac increased risk of cardiac arrest by 50% (OR 1.50, 95% CI 1.23 to 1.82)
  • use of naproxen was not associated with cardiac arrest, nor was use of COX-2 inhibitors

NSAID users were more likely to be women, have less cardiovascular disease, but be more likely to have cancer and rheumatic diseases. They were also more likely to be treated with psychiatric medication, diuretics and morphine.

Conclusions

The researchers concluded that,

“In a nationwide cohort of persons with OHCA [out-of-hospital cardiac arrest], we found that short-term treatment with non-selective NSAIDs, particularly ibuprofen and diclofenac, was associated with an increased early risk of cardiac arrest.

We found no association between cardiac arrest and use of the COX-2 selective inhibitors, rofecoxib and celecoxib, nor the non-selective NSAID naproxen.”

They went on to say:

“Our findings support the accumulating evidence of an unfavourable cardiovascular risk profile associated with use of the non-selective NSAIDs. This calls for special awareness in order to balance risks against benefits in treatment with NSAIDs.”

This study does have limitations:

  • Although the researchers used the same people to avoid confounding variables, the same person will differ in certain aspects over time – for example, certain diseases may get better or worse, which might have affected the results.
  • The study only looked at prescribed drugs and not over-the-counter drugs. In Denmark, ibuprofen was the only over-the-counter drug sold at the time of the study and therefore a large number of people taking ibuprofen might have been missed.
  • It could be that people are taking NSAIDs for other underlying problems that increase the risk of cardiac arrest, so it might be these problems increasing risk of cardiac arrest, not the NSAIDs.
  • The dose and duration of NSAIDs might have varied across participants. It’s not clear whether the greater the dose or duration, the higher the risk of cardiac arrest.
  • The study was carried out in Denmark – the findings might not be as relevant to other populations, who have different lifestyles.

If you’re unclear about whether you should be taking NSAIDs, please ask your GP or pharmacist for advice.

Kathrine B. Sondergaard, Peter Weeke, Mads Wissenberg, Anne-Marie Schjerning Olsen, Emil L. Fosbol, Freddy K. Lippert, Christian Torp-Pedersen, Gunnar H. Gislason, Fredrik Folke
Non-steroidal anti-inflammatory drug use is associated with increased risk of out-of-hospital cardiac arrest: a nationwide case–time–control study
Eur Heart J Cardiovasc Pharmacother (2017) 3 (2): 100-107. DOI: https://doi.org/10.1093/ehjcvp/pvw041

Image: Mk2010 CC BY-SA 3.0

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