Diclofenac has higher cardiovascular risk than other NSAIDs: study

The NSAID diclofenac has a higher cardiovascular risk than other NSAIDs, a Danish study suggests.

While the TGA already advises that NSAIDs increase cardiovascular risks and should be avoided in people with cardiovascular disease, a new analysis shows that diclofenac confers a higher risk than other traditional NSAIDs such as naproxen and ibuprofen.

Researchers examined the cardiovascular risks of diclofenac initiation compared with initiation of other NSAIDs and paracetamol based on Danish population based health registries  from 1996-2016.

Their study, published in the BMJ, included 1.4 million patients starting diclofenac, 3.9 million ibuprofen users, 292,000 naproxen users and 765,000 patients using paracetamol as well as 1.3 million people not using NSAIDs or paracetamol.

In terms of major adverse cardiovascular events within 30 days of starting a drug, patients taking diclofenac had a 30% higher incidence rate compared with naproxen users, a 20% higher rate than ibuprofen or paracetamol users and a 50% higher incidence rate than people not using any drug.

The increased risk with diclofenac was seen for atrial fibrillation or flutter, ischaemic stroke, heart failure, myocardial infarction, and cardiac death. It was also seen regardless of gender, age and even at low doses of diclofenac.

“Although the relative risk of major adverse cardiovascular events was highest in individuals with low or moderate baseline risk (that is, diabetes mellitus), the absolute risk was highest in individuals with high baseline risk (that is, previous myocardial infarction or heart failure),” the study authors noted.

Diclofenac was also associated with an increased risk of upper gastrointestinal bleeding at 30 days, by approximately 4.5-fold compared with no drug, 2.5-fold compared with  ibuprofen or paracetamol, and to a similar extent as naproxen use.

The study authors said the cardiovascular toxicity of diclofenac may arise from its short half life of one-two hours, requiring it to be prescribed in high doses that result in “a window of pure COX-2 inhibition” when plasma levels of the drug decline, an effect not seen with other NSAIDs.

Given the drug’s cardiovascular and gastrointestinal risks, there is little justification to use it first line before other traditional NSAIDs, they concluded.

“It is time to acknowledge the potential health risk of diclofenac and to reduce its use. Diclofenac should not be available over the counter, and when prescribed, should be accompanied by an appropriate front package warning about its potential risks,” they recommended.

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