Nonsteroidal anti-inflammatory drugs (NSAIDs) are prescribed to reduce pain and inflammation, particularly for arthritis. They are among the most widely used medications in the world. The first of the NSAIDs, aspirin, has been shown to reduce the risk of heart attack by 44%. In recent years, researchers have begun to examine whether nonaspirin NSAIDs provide a similar benefit. Nonaspirin NSAIDS are available in prescription strength and nonprescription strength. For example, prescription-strength ibuprofen is sold as Motrin 800 (among other names) and naproxen is available as Anaprox. When sold over-the-counter, ibuprofen is available as Motrin and Advil (among other names) and naproxen is sold as Aleve or Naprosyn.

Two studies recently published in the Archives of Internal Medicine suggest that prescription-strength naproxen may be the only nonaspirin NSAID that reduces the risk of heart attack.

About the studies

The two studies were conducted by two separate groups of researchers.

Nonaspirin NSAID use versus no NSAID use

Researchers from Harvard Medical School studied medical and prescription medication records in the following databases: New Jersey Medicaid and Medicare programs and the Pharmaceutical Assistance for the Aged and Disabled program. This study included 4425 patients who had a heart attack (cases) between January 1, 1991 and December 31, 1995 and 17,700 patients in the databases who had not had a heart attack (controls). Controls had visited the doctor for some other reason or had a prescription filled during the same time period between 1991 and 1995. They were matched to cases on the basis of age at the time of the corresponding case’s heart attack. Patients were excluded from the study if they had a history of regular aspirin or warfarin (Coumadin) use, heart attack, angina, coronary artery bypass graft, angioplasty, stroke, atrial fibrillation, chronic headache conditions (such as migraine), or rheumatoid arthritis.

Researchers compared the number of cases who filled prescriptions for NSAIDs in the six months prior to their heart attacks with the number of controls who filled prescriptions for NSAIDs in the same time period.

Naproxen use versus use of other nonaspirin NSAIDs

In a separate study funded by Merck & Co., the company that manufactures the NSAID rofecoxib (Vioxx), researchers from McGill University in Montreal and two Montreal hospitals compared naproxen use with use of other NSAIDs. They studied the medical and prescription medication records of people aged 65 and older in two government health care databases. This study included 14,163 patients who had a heart attack (cases) between January 1, 1992 and December 31, 1994 and 14,160 patients listed in the database who had not had a heart attack (controls). Controls had visited the doctor for some other reason or had a prescription filled during the same period between 1992 and 1994. They were matched to cases on the basis of age at the time of the corresponding case’s heart attack. Patients were excluded from the study if they had a history of heart attack. Note that people with other conditions known to increase the risk of heart attack (such as those excluded from the above study) and people taking aspirin or warfarin products were NOT excluded from this study.

Researchers compared the use of naproxen versus use of other NSAIDS among heart attack patients (cases) and patients who did not have a heart attack (controls).

The findings

Nonaspirin NSAID use versus no NSAID use

Overall, people who took nonaspirin NSAIDs had the same risk of heart attack as people who did not take NSAIDs. However, when the researchers examined the use of each type of NSAID individually, they found that people taking naproxen had a 16% lower risk of heart attack compared with nonusers of NSAIDs. Of note is that etodolac (Lodine) and fenoprofen (Nalfon) appeared to increase the risk of heart attack.

In calculating these statistics, the researchers accounted for other factors that may affect the risk of heart attack, such as age, sex, ethnicity, diabetes, high blood pressure, and congestive heart failure.

Although these results are interesting, there are limitations to this study. First, because cigarette smoking and obesity—two important risk factors for heart attack—were not assessed, their role in heart attack risk among study participants is unknown. Second, researchers measured NSAID use based on filled prescriptions for NSAIDs, so it is unknown whether participants also used over-the-counter NSAIDs, and how this would affect the results. Third, although patients filled their prescriptions, researchers did not verify that they took their entire prescriptions as directed. Fourth, the newer selective COX-2-inhibiting NSAIDs—rofecoxib (Vioxx) and celecoxib (Celebrex)—were not available during this study period, so their effects on heart attack risk are not known.

Naproxen use versus use of other nonaspirin NSAIDs

People taking naproxen had a 21% lower risk of heart attack than people taking other nonaspirin NSAIDs.

In calculating these statistics, the researchers accounted for the potential effects of other factors that affect heart attack risk, such as existing heart disease and use of lipid-lowering drugs, anticoagulant drugs (warfarin, Coumadin), nitrates, and blood pressure-lowering drugs.

Although these results are interesting, this study shares some of the same limitations of the above study. Again, cigarette smoking and obesity—two important risk factors for heart attack—were not assessed, so their role in this study is unknown. As in the first study, researchers measured NSAID use based on filled prescriptions for NSAIDs, so over-the-counter NSAID use is not accounted for. And again, although patients filled their prescriptions, researchers did not verify that they took their entire prescriptions as directed. Finally, the government health care databases used in this study do not contain information about patients who died of a heart attack before reaching the hospital, so their NSAID use is unknown.

How does this affect you?

Taken together, these two studies suggest that naproxen is the only nonaspirin NSAID that reduces the risk of heart attack. These findings also support the findings of other research suggesting that naproxen provides some benefit in reducing the risk of heart attack.

Is naproxen as good as aspirin at reducing heart attack risk? It doesn’t appear so. The current evidence suggests that naproxen reduces the risk of heart attack by about 21% and aspirin reduces the risk by about 44%. More research is needed to directly compare naproxen and aspirin. The authors of the studies and an independent reviewer, Dr. James Dalen, the journal’s editor, caution that aspirin is still considered the better drug for reducing heart attack risk. And don’t forget, these studies examined the effects of prescription-strength nonaspirin NSAIDS, not over-the-counter NSAIDs.

Many older people take prescription NSAIDs to relieve arthritis symptoms. By virtue of their age, these same people are at increased risk for heart attack. A study published in November of 2000 found that the NSAID rofecoxib (Vioxx) increased the risk of heart attack compared with naproxen. These two new studies in Archives suggest that the apparent increased heart attack risk associated with rofecoxib was likely a result of the beneficial effects of naproxen rather than any hazardous effects of rofecoxib.