Some anti-inflammatory painkillers raise the risk of heart attack or stroke by a third or more in patients already being treated for heart problems, a new review concludes.

Researchers examined data from 51 large studies on the drug interaction between certain non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen (Advil), diclofenac (Voltaren) and indomethacin (Indocin) and cardiovascular risk. For ibuprofen, the authors suggested strengthening the labels to warn patients at high risk of cardiovascular disease from taking more than the maximum recommended dose without a prescription. Jack Guez/AFP/Getty

This is the first time that investigators said they had enough data to make direct comparisons among drugs to determine which products carry more risk for patients with heart problems.

After reviewing research from Europe, the U.S., Canada and Australia, Dr. David Henry of the Institute for Clinical Evaluative Sciences (ICES) in Toronto and Patricia McGettigan of Hull York Medical School in the UK concluded that for drugs popular in North America:

• The highest overall risks were seen with diclofenac, indomethacin and etodolac (brands include Lodine).
• The lowest observed risks were with naproxen (brands include Aleve, Naprosyn).
• Among the most widely used NSAIDs, naproxen and low-dose ibuprofen (brands such as Motrin, Advil, Nuprin) were least likely to increase cardiovascular risk.
• The risk with ibuprofen rose when the dose is higher than 1,200 mg per day.

The study's authors estimated that one in 50 heart patients might suffer an avoidable heart attack when taking diclofenac.

Henry, who is CEO of ICES, is concerned about heart patients not casual users of NSAIDS.

"That absolute increase of two per cent of having a heart attack is something you would actually worry about and want to avoid."

Guide for clinical decisions

For ibuprofen, the authors suggested strengthening the labels to warn patients at high risk of cardiovascular disease from taking more than 1,200 milligrams, the maximum recommended daily dose without a prescription.

"From a clinical perspective, naproxen and low-dose ibuprofen have the most favourable cardiovascular risk profiles. This advantage has to be weighed against the drugs' gastrointestinal risks," they concluded.

Many of the studies that were reviewed relied on hospital and administrative databases, and the reviewers did not have access to patient histories, the authors acknowledged in Tuesday's issue of the journal PLoS Medicine.

An editor's summary accompanying the article said the information will help clinical and regulatory decisions.

"Indomethacin is an older, rather toxic drug, and the new evidence on cardiovascular risk casts doubt on its continued clinical use," the editorial noted.

The findings are interesting but "by no means are conclusive," said Dr. Muhammad Mamdani, a pharmacologist and director of the Applied Health Research Centre, part of the Li Ka Shing Knowledge Institute at Toronto's St. Michael's Hospital.

The review, called a meta-analysis is based on observational studies that can't show a cause-and-effect relationship, said Mamdani, who was not involved in the study.

With files from The Canadian Press