A large study of several popular painkillers has confirmed that using them long-term carries significant risks of heart disease and stroke.
The Swiss study combined 31 randomised, controlled trials in various countries involving 116,000 patients.
"Although uncertainty remains", the University of Bern researchers wrote in the British Medical Journal, "little evidence exists to suggest that any of the investigated drugs are safe in cardiovascular terms. Naproxen seemed least harmful.
"Cardiovascular risk needs to be taken into account when prescribing any non-steroidal anti-inflammatory drug [NSAID]."
The study covers older NSAIDs like ibuprofen and diclofenac and some of the newer ones, "cox-2 inhibitors" whose chemical names end in " coxib" and which are generally associated with a lower risk of stomach disorders such as bleeding.
Two of the drugs have been withdrawn from sale - Vioxx because of deaths from cardiovascular disease, and Prexige because of liver toxicity.
NSAIDs are commonly used by people with arthritis and other painful conditions. The BMJ paper says in the United States it is estimated that 5 per cent of all visits to a doctor are related to prescriptions for these medicines.
The Swiss study found ibuprofen was associated with the highest risk of stroke, which was more than three times higher than for people taking placebo pills; followed by diclofenac.
Arcoxia had the highest risk of death from cardiovascular disease - more than four times higher than for a placebo - followed by diclofenac at a risk 3.98 times that of a placebo. Vioxx had the highest heart attack risk, followed by Prexige, then ibuprofen on 1.61 times that for people on a placebo.
However, the researchers noted that although their analysis covered more than 100,000 patient-years of follow-up, "The number of events for most outcomes was low and our estimates of rate ratios imprecise ..."
Government drugs regulator Medsafe said yesterday the Swiss study confirmed the risks of NSAIDs.
"As with all painkillers, Medsafe advises using the lowest effective dose for the shortest time possible. Patients are advised to discuss any concerns they may have with their doctor," said senior pharmacovigilance adviser, Dr Susan Kenyon.
Tim Roper, executive director of the association representing suppliers of non-prescription medicines, said the study was based on long-term prescription doses of the drugs.
He said over-the-counter ibuprofen and naproxen had a long history of safety and effectiveness when taken for the short-term relief of pain and fever.
The study looked at seven non-steroidal anti-inflammatories:
Naproxen - sold under brands including Naproxyn and Naxen.
Ibuprofen - Nurofen, Brufen.
Diclofenac - Voltaren, Cataflam.
Celecoxib - Celebrex
Etoricoxib - Arcoxia
Rofecoxib - Vioxx (withdrawn from sale internationally in 2004).
Lumiracoxib - Prexige (withdrawn from sale in New Zealand in 2007, and from many other countries then and later).