A meta-analysis published in the Lancet found that prescription doses of older NSAIDs diclofenac and ibuprofen can increase the risk of heart problems.
For every 1,000 patients with a moderate risk of heart disease taking these drugs for a year, three more would develop an avoidable MI, of which one would die.
Patients with underlying risk factors faced the greatest risk. Researchers said the findings could allow clinicians to decide on the safest regimen for their patients.
Older NSAIDs had been linked to gastrointestinal problems, while some newer generation selective COX-2 inhibitors (coxibs) were associated with an increased risk of vascular events. It had remained unclear how these risks differed between drugs and regimens, however, and whether the heart risks were similar in the older NSAIDs.
In the study, University of Oxford researchers analysed results from 639 trials that compared one NSAID with another, or against a placebo. These included data on over 350,000 patients. Most patients taking NSAIDs were being treated for rheumatoid arthritis or osteoarthritis.
MI risk 'doubled'
The study examined findings for coxibs as well as high doses of diclofenac (150mg), ibuprofen (2400mg), and naproxen (1000mg).
Risk of major vascular events, including MI and vascular death, rose by 37% among those taking coxibs and by 41% for those on diclofenac.
Patients taking ibuprofen were more than twice as likely as those on placebo to develop MI. However, naproxen was not linked to greater risk of major vascular or coronary events.
All NSAIDs doubled the risk of hospitalisation for heart failure, while rates of gastrointestinal complications, mostly bleeds, rose by up to four-fold among patients taking these drugs, although only 2% were fatal.
There was no increased risk of stroke for any NSAIDs studied.
However, researchers found the extent of the risk could be predicted by the underlying risk of heart disease. Patients with a history of heart disease or risk factors such as high BP faced the greatest risk from the treatments.
Lead author Professor Colin Baigent from the University of Oxford said: 'Whilst NSAIDs increase vascular and gastrointestinal risks to a varying extent, our analyses indicate that the effects of different regimens in particular patients can be predicted, which may help physicians choosing between alternative NSAID regimens to weigh up which type of NSAID is safest in different patients.'
In an editorial, Professor Marie Griffin from Vanderbilt University Medical Center in the US said that although the study gives certainty about the risks of high-dose, commonly used NSAIDs, it leaves 'large gaps' about risks relating to lower doses, duration of use and residual effects after treatment ends.
She added: 'Identification of safe and effective strategies for chronic pain is sorely needed. In the meantime, long-term use of high dose NSAIDs should be reserved for those who receive considerable symptomatic benefit from the treatment and understand the risks.'