September 28, 2016

expert reaction to study on painkillers and heart failure

A group of researchers have published their work in The BMJ examining the effect of non-steroidal anti-inflammatory drugs (NSAIDs) and report that use of such drugs can increase the risk of heart failure.

Helen Williams, Consultant Pharmacist for Cardiovascular Disease at the Royal Pharmaceutical Society, said:

“The link between use of NSAIDs and increased risk of heart failure is well-established. This paper helps to quantify the risk with individual NSAID medicines and assesses the impact of different doses. It also indicates that using this group of medicines, particularly at higher doses, is also associated with a higher risk of admission to hospital due to heart failure.

“Over recent years, the NHS has moved away from more the potent NSAIDs, (such as indomethacin, piroxicam, and even diclofenac) because of the established increased risk of heart attacks and strokes with these medicines.

“Reassuringly, use of the most commonly purchased NSAID, ibuprofen, was associated with a lower overall increased risk of hospitalisation due to heart failure when compared to the other medicines. Similarly, naproxen, a commonly prescribed NSAID, had a relatively lower risk. Only current use of celecoxib was associated with no increased risk of hospitalisation due to heart failure.

“The study reinforces the need to carefully weigh up the risks and benefits of using NSAIDs. Measures to help reduce risk include using medicines with a lower risk of cardiovascular problems, minimising the prescribed dose to the lowest dose that is effective and where possible, limiting the length of time the patient takes the medicine.

“People regularly purchasing NSAIDs over the counter, such as ibuprofen, should seek advice from their pharmacist or doctor. People needing treatment with long-term or frequent short courses of NSAIDs do need careful monitoring, such as kidney checks and should be regularly assessed to ensure the on-going suitability of NSAID therapy for them.”

Prof. Stephen Evans, Professor of Pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, said:

“This is a real, but for most patients, very small risk. The risk is shown in this paper to increase with dose. In general, this has been known for a long time and higher quality data from randomised trials have also shown these effects on heart failure and also on other cardiovascular effects.

“This study, well conducted, does show some evidence, generally consistent with randomised trials, that there are some differences between different drugs. It is possible that some of these differences are due to different effective doses for the different drugs.

“The absolute risk is suggested to be about 37.5 admissions for heart failure per 10,000 person years. Because of the study design, it is possible that this is an over-estimate but it is of the right order of magnitude. The rate of admission increases dramatically with age and it is important to remember the average age of the people studied here was 77 years.

“The consequence is that it is of very little relevance to most people below age 65 taking painkillers, but in the very elderly (say above 80) that the effects are of more relevance.  For individuals it is a small increased risk.”

Prof. Peter Weissberg, Medical Director at the British Heart Foundation, said:

“This large observational study reinforces previous research showing that some NSAIDs, a group of drugs commonly taken by patients with joint problems, increase the risk of developing heart failure.

“It has been known for some years now that such drugs need to be used with caution in patients with, or at high risk of, heart disease. This applies mostly to those who take them on a daily basis rather than only occasionally.

“Since heart and joint problems often coexist, particularly in the elderly, this study serves as a reminder to doctors to consider carefully how they prescribe NSAIDs, and to patients that they should only take the lowest effective dose for the shortest possible time. They should discuss their treatment with their GP if they have any concerns.”

Dr Tim Chico, Reader in Cardiovascular Medicine at the University of Sheffield, said:

“This is a carefully conducted study that looked at the medical records of over 8 million patients to try to determine whether NSAIDs increase the risk of heart failure and by how much. The results are consistent with other studies which have shown that these drugs increase the risk of being admitted with heart failure. Overall, NSAIDs were associated with a 1.19 times higher risk.  Fortunately, however, the risks of a short course of ibuprofen in people without evidence of heart disease remain low.

“Heart failure is caused by a wide range of conditions, including high blood pressure, heart attacks, alcohol, and obesity. It seems unlikely that NSAIDs would cause problems in people with otherwise healthy hearts, but they may unmask heart failure due to these other causes. This means that we can reduce our overall risk of heart disease by maintaining a healthy weight and blood pressure, a healthy diet, not smoking, and regular physical activity, irrespective of whether or not we have health problems that may require NSAIDs.

“All drugs have the potential to cause side effects or other unwanted consequences, so it is essential to discuss the possible risks and benefits of any drug with your doctor. Although many people will continue to take NSAIDs long term, they should be aware of the alternatives, and take the lowest dose that is effective for their pain. Patients known to have heart failure already should not be taking NSAIDs unless they have been fully informed of the risks and any alternative treatments.”

Prof. David Webb, President of the British Pharmacological Society, said:

“We already know that non-steroidal anti-inflammatory drugs (NSAIDs) have effects on the kidney to cause salt and water retention in the body, which may predispose to heart failure. We also know that they make some blood pressure-lowering medicines, such as ACE inhibitors and diuretics, less effective, and that a rise in blood pressure is one of the major factors leading to worsening of heart failure. These mechanisms are well known as is the fact that NSAIDs can cause worsening of heart failure.”

“This case-control study from 4 countries in almost 100,000 patients with heart failure and 8 million controls suggests that NSAID use is associated with an almost 20% increased risk of hospital admission with heart failure. Importantly, it showed that some commonly used traditional NSAIDs, like indomethacin, were much more likely to cause heart failure admissions than diclofenac, and that there were also high risks with some prescribed drugs, and a low risk with others, such as celecoxib. This will be important and valuable new information for prescribers and regulators in protecting patients who need NSAIDs from hospital admissions with heart failure.”

‘Non-steroidal anti-inflammatory drugs and risk of heart failure in four European countries: nested case-control study’ by Andrea Arfè et al. published in The BMJ Wednesday 28 September 2016. 

Declared interests

Prof. Evans: I am an independent expert member of the EU drug safety committee (PRAC) at the European Medicines Agency