What You Need to Know About NSAIDs Pain Relievers and Heart Disease Risk

So, you overdid it at the gym…again. This time, though, you may want to rethink your choice of pain reliever.

Treating soreness, aches, and pains with over-the-counter NSAID (non-steroidal anti-inflammatory) drugs is common. But a new study, published in the journal Circulation: Cardiovascular Quality and Outcomes, found a link between regular use of one NSAID, naproxen, and an increased risk of heart attack and stroke in women. Regular use was defined as at least twice per week for the previous two weeks.

The study, led by researchers from the University of Florida, confirmed that regular use of NSAIDs increased the risk of digestive bleeding. It also found that naproxen, the active ingredient in pain relievers like Aleve, increased the risk of stroke, heart attack, and death in postmenopausal women by 10 percent.

While previous studies have demonstrated that NSAIDs increase the risk for heart attack and stroke, others have documented a reduced frequency of such events. This is the first study that found an association between an elevated risk of heart attack and stroke and naproxen in particular.

NSAIDs and the Heart

NSAIDs work by inhibiting the cox-1 and cox-2 enzymes, which are responsible for inflammation in the body. There are several kinds of NSAIDs, including those that that selectively target cox-2, which are known to increase heart attack and stroke. (You may remember the cox-2 enzyme inhibitor Vioxx, which was removed from the market in 2004 due to such risks.)

To explore whether nonselective NSAIDs (those that inhibit both the cox-1 and cox-2 enzymes) created similar risks, the research team looked at the use of three categories of NSAIDS: those that inhibit cox-2 (such as Celebrex); those that inhibit cox-2 more than cox-1 (such as naproxen); and those that inhibit cox-1 more than cox-2 (such as ibuprofen).

The researchers, led by principal investigator and study co-author Marian Limacher, MD, professor of medicine at the University of Florida, analyzed data from more than 160,000 postmenopausal women who were surveyed as part of the Women’s Health Initiative, a 15-year research study funded by the National Institutes of Health.

Of these women, 53,142 regularly used NSAIDs. Researchers found the increased risk for heart attack, stroke, or death among the women who used naproxen, even after controlling for factors such as obesity, hypertension, diabetes, and use of aspirin.

This was an observational study, and only shows an association, rather than a definitive cause-and-effect relationship, with an increased risk of disease. Nonetheless, the take-away is that NSAIDs—including over-the-counter medications—should be used with caution, especially in people already at an increased risk for heart disease.

Over-the-counter NSAIDs include:

  • Aspirin*
  • Naproxen (Aleve)
  • Ibuprofen** (Advil, Motrin)

Prescription-only NSAIDs include:

  • Celecoxib (Celebrex)
  • Diclofenac (Cataflam, Voltaren, Arthrotec, combined with misoprostol)
  • Diflunisal (Dolobid)
  • Etodolac (Lodine, Lodine XL)
  • Fenoprofen (Nalfon, Nalfon 200)
  • Flurbiprofen (Ansaid)
  • Ibuprofen (Motrin, Tab-Profen, Vicoprofen, combined with hydrocodone, and Combunox, combined with oxycodone)
  • Indomethacin (Indocin, Indocin SR, Ind0-Lemmon, Indomethagan)
  • Ketoprofen (Oruvail)
  • Ketorolac (Toradol)
  • Mefenamic Acid (Ponstel)
  • Meloxicam (Mobic)
  • Nabumetone (Relafen)
  • Naproxen (Naprosyn, Anaprox, Anaprox DS, EC-Naprosyn, Naprelan, Naprapace, copackaged with Iansoprazole)
  • Oxaprozin (Daypro)
  • Piroxicam (Feldene)
  • Sulindac (Clinoral)
  • Tolmetin (Tolectin, Tolectin DS, Tolectin 600)

*Aspirin is the only NSAID recommended for prevention of heart attack and stroke in people at higher risk of cardiovascular disease.

**In the University of Florida study, ibuprofen was not associated with an increased risk of heart attack and stroke in postmenopausal women.

How to Protect Your Heart While Seeking Pain Relief

Here are some of ways you can find relief—without risking your health:

  • Think outside the over-the-counter box and "Consider other methods for pain relief, including rest, heat, and physical therapy," Limacher says.
  • If you do take pain relievers, "Use the lowest effective dose for the shortest possible duration," Limacher says. Though her study focused on women and NSAIDs, she gives this advice to both women and men.
  • Choose ibuprofen or aspirin. Aspirin lowers risk of stroke (and has been found to lower rates for first heart attack in men, but not women).
  • Try acetaminophen (Tylenol), but know that it only reduces pain—it does not help reduce inflammation.

The study didn’t look at the effects of NSAIDs on kidneys or other side effects such as bleeding. So Limacher advises women using the pain relievers regularly to follow up with their physicians to monitor effects on the kidneys—as well as the heart.

Bottom line: If you have cardiovascular disease, discuss NSAID use with your physician.

Marian C. Limacher, MD, Professor of Medicine, University of Florida, and UF principal investigator for the Women’s Health Initiative, reviewed this article.


Sherbourne, Morgan. "UF Research Finds Association Between Certain Pain Relievers and Heart Attack." University of Florida College of Medicine Insider. July 9, 2014. 

Bavry, Anthony A., Fridtjof Thomas, Matthew Allison, Karen C. Johnson, Barbara V. Howard, Mark Hlatky, JoAnn E. Manson, Marian C. Limacher. "Nonsteroidal Anti-Inflammatory Drugs and Cardiovascular Outcomes in Women: Results From the Women’s Health Initiative." Circulation: Cardiovascular Quality and Outcomes 7 (2014):603-610. Published online July 8, 2014. Doi: 10.1161/CIRCOUTCOMES.113.000800 

"Medications Guide for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)." FDA. http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020938s020,021530s008MedGuide.pdf