The commonly used painkiller diclofenac is associated with an increased risk of major cardiovascular events, according to a study in Denmark.
It found the risk from diclofenac was higher compared with not using the drug, paracetamol use and also use of other traditional painkillers, the researchers said in the British Medical Journal.
“There is little justification to initiate diclofenac treatment before other traditional NSAIDs”
The researchers behind the study said it was time to acknowledge the potential health risks from the non-steroidal anti-inflammatory drug and reduce its use globally, following previous concerns about its links to cardiovascular conditions.
As a result, they said the painkiller should not generally be available over the counter, and when prescribed, should be accompanied by an appropriate front package warning about its potential risks.
In 2015, the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) said diclofenac tablets would no longer be available to patients without a prescription due to the small risk of heart problems.
It followed the publication a year earlier of a trial summary on the cardiovascular safety of COX-2 inhibitors and non-selective NSAIDs, which advised against using diclofenac for patients with established ischaemic heart disease, peripheral arterial disease, cerebrovascular disease or congestive heart failure.
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In the new study, researchers examined the cardiovascular risks of starting diclofenac compared with no NSAIDS, starting other traditional NSAIDs – ibuprofen or naproxen – and starting paracetamol.
They used data from a national registry data for more than 6.3 million adults in Denmark with at least one year of continuous prescription records before study entry in January 1996.
Participants were split into low, moderate, and high baseline cardiovascular risk. Average age was 46-49 years among participants starting NSAIDs and 56 years among those starting paracetamol.
Starting diclofenac during the 10-year study period was associated with an increased rate of major adverse cardiovascular events within 30 days compared with ibuprofen, naproxen or paracetamol.
Events included irregular heart beat or flutter, ischaemic stroke, heart failure, and heart attack. The increased risks applied to men and women of all ages and also at low doses of diclofenac.
Starting diclofenac was also associated with an increased rate of cardiac death compared with no NSAIDs, said the researchers, led by Morten Schmidt at Aarhus University Hospital.
In addition, it was linked to an increased risk of upper gastrointestinal bleeding compared with no NSAIDs, starting ibuprofen or paracetamol, but not with naproxen.
However, the study authors highlighted that, while the relative risk was increased, the absolute risk – based on the number of events per 1,000 diclofenac starters per year – remained low for each patient.
“NSAIDs may be worthwhile for some patients to improve quality of life despite potential side effects”
For example, among patients at low baseline risk, diclofenac starters had one additional event versus ibuprofen starters, one additional event versus naproxen starters, three additional events versus paracetamol starters, and four additional events versus no NSAIDs.
Among patients at moderate baseline risk, corresponding figures were seven, seven, eight, and 14 additional events, and for those at high baseline risk the numbers were 16, 10, one, and 39 events.
The authors said their study provided strong evidence to guide clinical decision making, highlighting that its sample size was larger than most previous reviews of observational and randomised studies.
“Treatment of pain and inflammation with NSAIDs may be worthwhile for some patients to improve quality of life despite potential side effects,” said the researchers.
“Considering its cardiovascular and gastrointestinal risks, however, there is little justification to initiate diclofenac treatment before other traditional NSAIDs,” they added.