Database Studies May Not Accurately Estimate Risk of MI in Naproxen, Ibuprofen Users

It is well known that Aspirin, a non-selective, non-steroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX), reduces the risk of Heart Attack and stroke. Non-aspirin non-steroidal anti-inflammatory drugs (NANSAIDs) such as ibuprofen and naproxen may reduce this same risk, but studies have shown conflicting results. Some have shown no association between NANSAIDs and Heart Attacks; some have shown an increased risk; and others have suggested a lower risk of Heart Attack, particularly with naproxen.

A new epidemiological study from the University of Pennsylvania School of Medicine, based on detailed patient surveys rather than administrative databases of patient prescriptions and billing records, suggests that these administrative-database studies may not accurately estimate the risk of Heart Attack among users of naproxen and ibuprofen.

Indeed, results from the Penn study showed a protective relationship between NANSAIDs and Heart Attack. The study findings are published in the August issue of Pharmacoepidemiology and Drug Safety, and will be presented at the 21st International Conference on Pharmacoepidemiology and Therapeutic Risk Management (www.pharmacoepi.epi) on August 23 in Nashville, TN.

Previous studies on NANSAIDs used prescription records from billing data or electronic medical records (referred to as "electronic databases"), but not direct interviews with patients about their lifestyle or their over-the-counter use of NANSAIDs or aspirin. However, a February 2005 study by lead author Stephen E. Kimmel, MD, Associate Professor of Medicine in the Cardiovascular Division and Associate Professor of Epidemiology in the Department of Biostatistics and Epidemiology at Penn, suggested a benefit of non-selective NANSAIDs, when data were collected from study participants instead of relying on the limited information from electronic databases.

Although all epidemiological studies have potential limitations, electronic databases have several limitations inherent in the source of data: First, electronic databases record only prescription records, not over­-the-counter use, so most use of NANSAIDs like over-the-counter ibuprofen is unaccounted for. "By using prescription databases you don't completely capture the non-steroidal use," says Kimmel. "You are calling people non-users of the drug when they really are. In our survey, 35 percent of participants had taken a non-steroidal, mostly over-the-counter, in the week prior to taking our survey."

This misclassification of users as non-users of NANSAIDs skews interpretation toward finding that NANSAIDs have no effect on the risk of Heart Attacks. The researchers found that of all the non-steroidal use, 80% was over the counter, and mostly ibuprofen (e.g., Advil).