Expert reaction to new research on painkillers and heart attacks/strokes

Experts react to a study published in the British Medical Journal that suggests that commonly used painkillers increase the risk of heart attacks and strokes when taken at high doses or over the long term, according to new research. The comments below were gathered by our colleagues at the Science Media Centre in London.

Professor Simon Maxwell, Chair of the British Pharmacological Society’s Prescribing Committee and Professor of Clinical Pharmacology at the University of Edinburgh, said:

“This paper adds to the growing body of evidence that regular use of NSAID drugs (e.g. ibuprofen) is associated with a small but measurable excess risk of cardiovascular events.

“While this finding may be a cause of alarm to some it should be seen in context. Most users of these drugs will only take them for a relatively brief duration to treat short lasting episodes of pain and are at minimal risk. Patients with chronic pain may find themselves using such drugs for more prolonged periods. While this study suggests they might be exposed to some excess risk the alternatives may be less acceptable. Living with pain severely impairs quality of life. Alternative painkillers are also associated with very real adverse effects which are arguably less acceptable.

“The advice to the public should continue to be to take this class of drugs only when they are genuinely necessary to control pain and in the lowest effective dose, not only because of any cardiovascular risk but also because of potential effects on the stomach.”

Professor Philip Bath, member of the British Pharmacological Society and Stroke Association, and Professor of Stroke Medicine at the University of Nottingham, said:

“The work by Trelle and colleagues is important because it reminds us that non-steroidal anti-inflammatory drugs (NSAIDs) carry potential disadvantages as well as the benefit of being useful pain killers. Using data from 31 randomised controlled trials, and the statistical technique of network meta-analysis, the paper shows that taking either older NSAIDs, such as ibuprofen and diclofenac, or newer NSAIDs, such as rofecoxib, may increase the risk of stroke, heart attack and vascular death.

“While it is conceivable that the drugs are toxic to blood vessels and their contents, as they are to the kidney, it is also possible that negative effects of stroke and heart attack are because NSAIDs reduce the effect of other beneficial drugs such as aspirin.

“Whatever the cause, physicians and patients need to balance the benefits of using NSAIDs to reduce pain, sometimes excruciating, with the hazards of using these drugs, which can include gastric bleeding and kidney impairment. This balance needs to take account of the availability of other painkillers, including paracetamol and opiates. But if a NSAID is needed, as it often will be, then this new work suggest that naproxen may be the safest drug in people who have previously had a stroke or heart attack.

Professor Donald Singer, member of the British Pharmacological Society and Professor of Clinical Pharmacology and Therapeutics at the University of Warwick, said:

“This is an interesting but complex study aiming to use new statistical methods to compare cardiovascular risks between non-steroidal anti-inflammatory drugs [NSAIDs] and against placebo across many studies when those contrasts are not available from direct comparative studies.

“There are two main cautions about these findings. First, headline results are given as relative risks. It is very important to be given clear information on absolute rates adjusted for other obvious risks in these older populations studied. Second, the statistical approach used by the authors is at risk of bias: apparent differences in risk between treatments may be due to differences between study groups rather than to differences between drugs.

“For the method in this paper (network meta-analysis) treatment groups should have very similar characteristics. However there are obvious differences among treatment groups. That can be seen from the wide (around 3-fold) difference in stroke rates on placebo treatment in different studies [25 to 82 strokes per 10,000 patient years of treatment]. And, for example, although ibuprofen is flagged as linked to higher stroke risk, the actual risk of stroke in the ibuprofen studies appeared low and within the range for many of the placebo studies [24 and 53 strokes per 10,000 patient years of treatment].

“Furthermore we are not told about adjustments across treatment groups for degree of cardiovascular risk burden as a source of bias and the authors acknowledge that some of their findings are imprecise. Pending further information, it would seem sensible to be cautious and to take into account cardiovascular risk when NSAIDs are prescribed or obtained over the counter.”

Sotiris Antoniou, Consultant Pharmacist, Cardiovascular Medicine, Royal Pharmaceutical Society:

“The studies carried out in this research are based on chronic and maximum doses of ibuprofen, taken for at least a year. Pharmacists have been aware of the small increased risk of cardiovascular events associated with high doses (2400mg daily) of ibuprofen for long term treatment, in line with clinical trial evidence and research to date. As such, it is always recommended to use the lowest effective dose for the shortest duration of treatment.

“The dose used most commonly by people is a low dose of 200mg – 400mg up to three times a day i.e. taken intermittently in line with the individual OTC product licenses. Overall there is no suggestion in these studies that low dose ibuprofen (less than 1200mg daily) is associated with an increased cardiovascular risk.”

*Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis, Trelle, S. et al, BMJ 2011;342:c7086 will be published in the British Medical Journal at 2330hrs UK Time Tuesday 11 January 2011, which is also when the embargo will lift.