The study, published in the BMJ, suggests that diclofenac use significantly increases the risk of major cardiovascular events compared with no NSAID use, paracetamol use and use of other traditional NSAIDs.
Using data from Danish population-based health registries, the researchers performed a series of 252 nationwide cohort studies mimicking the design criteria of a clinical trial, in order to examine the cardiovascular risks of diclofenac.
The studies included 1,370,832 initiators of diclofenac, 3,878,454 initiators of ibuprofen, 291,490 initiators of naproxen, 764,781 healthcare-seeking initiators of paracetamol (matched by propensity score), and 1,303,209 healthcare-seeking NSAID non-initiators (also matched by propensity score).
The incidence rate ratio of major adverse cardiovascular events at 30 days was increased by 50% in diclofenac initiators compared with non-initiators, by 20% compared with ibuprofen or paracetamol initiators, and by 30% compared with naproxen initiators.
The increased risk was observed for atrial fibrillation or flutter, ischaemic stroke, heart failure, myocardial infarction, and cardiac death; both sexes of all ages; and even at low doses of diclofenac.
The risk of upper gastrointestinal bleeding at 30 days with diclofenac was similar to that of naproxen, but considerably higher than for no NSAID initiation, paracetamol, and ibuprofen.
The researchers call for the use of diclofenac to be reduced and restricted to prescription only, accompanied by a prominent warning about the potential risks.
'Treatment of pain and inflammation with NSAIDs may be worthwhile for some patients to improve quality of life despite potential side effects,' they acknowledge. 'Considering its cardiovascular and gastrointestinal risks, however, there is little justification to initiate diclofenac treatment before other traditional NSAIDs.'