Swiss researchers analyzed the results of 31 trials involving seven non-steroidal anti-inflammatory drugs (NSAIDs), as these medications are called, and concluded that cardiovascular risk needs to be considered before prescribing any of them.
“NSAIDs are widely used worldwide for treating pain and inflammation,” said Dr. Gregg Fonarow, American Heart Association spokesman and professor of cardiology at the University of California, Los Angeles.
“A number of studies have shown that many of these agents are associated with increased risk of cardiovascular events, particularly when used at higher doses and for longer periods of time, but uncertainty remains as to the magnitude of the risk and how the cardiovascular risk may vary among different NSAIDs,” said Fonarow, who was not involved in the study.
All the NSAIDs studied increased the risk of cardiovascular events, but the magnitude of risk is small in absolute terms — approximately one cardiovascular event per 100 patient-years of follow-up, Fonarow noted.
“In many patients the benefits provided by these agents may outweigh the risk, and other steps can be taken to reduce the patient’s cardiovascular risk,” he said.
The report is published in the Jan. 11 online edition of the BMJ.
In 2004, the drug Vioxx (rofecoxib), which belonged to a class of NSAIDs called COX-2 inhibitors, was pulled from the market because of its link to an increased risk of heart attack.
To explore the connection between NSAIDs and heart problems, a team led by Dr. Peter Juni, from the Institute of Social and Preventive Medicine at the University of Bern, reviewed 31 trials that included 116,429 patients. This method of reviewing trial findings to uncover a pattern is called a meta-analysis.
The painkillers the patients were taking included naproxen (Aleve), ibuprofen (Advil, Motrin), diclofenac (Voltaren, Cataflam), celecoxib (Celebrex), etoricoxib (Arcoxia), rofecoxib (Vioxx), lumiracoxib (Prexige) or placebo.
Overall, the number of heart events among patients taking NSAIDs was low, the researchers found. In 29 trials, 554 heart attacks occurred. In 26 trials, 377 strokes were reported, and in 28 trials, 676 people died.
Compared with patients taking placebo, those taking rofecoxib and lumiracoxib had twice the risk of heart attack, and those taking ibuprofen had more than three times the risk of stroke. The highest risks for cardiac death were associated with etoricoxib and diclofenac, where the risk was around four times greater than for placebo, the researchers found.
Naproxen appeared to be the least harmful medication, they noted.
“Our study provides the best available evidence on the safety of this class of drugs,” the researchers wrote. “Although uncertainty remains, little evidence exists to suggest that any of the investigated drugs are safe in cardiovascular terms. Cardiovascular risk needs to be taken into account when prescribing any non-steroidal anti-inflammatory drug,” they concluded.
Commenting on the study, Dr. Eric J. Topol, director of the Scripps Translational Science Institute and one of the experts who uncovered the risks associated with Vioxx, said a meta-analysis can leave many questions unanswered but is of value nonetheless.
“Pooling large data sets like this winds up with ambiguity as it homogenizes differences in patient population characteristics, dose of drugs, how endpoints were ascertained and when, etc.,” he said. “I am not sure if the conclusions reflect or agree with other meta-analysis results,” Topol noted.
“Despite the limitations, this study has made many excellent contributions on the NSAID issue, so we need to factor these into the mix,” Topol said.