The use of oral nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of acute myocardial infarction (MI), according to a meta-analysis of individual patient data.

“Overall, this study found that a person’s baseline risk of an acute myocardial infarction is increased by about 20 percent to 50 percent with the use of commonly available NSAIDs,” Dr. Michelle Bally from Centre Hospitalier de l’Universite de Montreal, in Quebec, Canada, told Reuters Health by email. “For putting the MI risk in perspective, it may be useful to present risk of acute MI due to NSAIDs as averaging about 1 percent annually.”

Several randomized controlled trials have indicated an increased risk of acute MI associated with oral NSAIDs, but these studies were generally small and had poor generalizability.

Dr. Bally and colleagues used data from more than 61,000 cases and some 385,000 controls to determine the time course for risk of acute MI and the effects of dose and duration of continuous use for the most commonly used NSAIDs.

The increased risk of acute MI associated with current NSAID use ranged from 20 percent to 50 percent overall, with possible increases of 75 percent for ibuprofen and naproxen and more than a 100 percent increase for rofecoxib, the team reports in The BMJ, online May 9.

The meta-analysis suggests that the risk of MI associated with NSAID use increases immediately with exposure, particularly with higher doses, but duration of treatment does not seem to be associated with greater probabilities of increased MI risk.

“This study reveals a new finding, which is that for all common NSAIDs the risk of acute myocardial infarction starts as early as in the first 1 to 7 days of use,” Dr. Bally said. “The early onset of risk was the most surprising finding. Had we not looked at risk over this very short time window we would not have been able to discern an early depletion of susceptibles effect nor would we have seen the second wave of depletion of susceptibles with short-term (8 to 30 days) use of high dose rofecoxib, ibuprofen, and naproxen.”

The risk of acute MI appears to decrease over time since the last use of an NSAID.

“The data in our study allowed us to conclude with greater than 90 percent probability that all NSAIDs studied are associated with a heightened risk of acute myocardial infarction,” Dr. Bally said. “While this probability expresses the confidence in our results, our study is based on NSAID prescribing or dispensing and not all potentially influential factors could be taken into account.”

“Given that the onset of risk of acute myocardial infarction occurred in the first week and appeared greatest in the first month of treatment with higher doses, prescribers should consider weighing the risks and benefits of NSAIDs before instituting treatment, particularly for higher doses,” the researchers conclude.