By Pat Anson, Editor
Researchers have known for many years that non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of heart attack and stroke. Now they may finally be learning why the pain relievers can be harmful.
In experiments on heart cells from rats and mice, scientists at the University of California, Davis, found that NSAIDs reduced the activity of cardiac cells at pharmacological levels found in humans. Their study was recently published in the Journal of Molecular and Cellular Cardiology.
“We knew these non-steroidal anti-inflammatories had negative side effects for heart disease and stroke risk, “ said lead author Aldrin Gomes, a UC Davis associate professor of Neurobiology, Physiology and Behavior. “But now we have an idea of some of the mechanisms behind it.”
NSAIDs are widely used to treat everything from fever and headache to low back pain and arthritis. They are found in so many different products -- such as ibuprofen, Advil and Motrin -- that many consumers may not be aware how often they use NSAIDs.
Several studies have found that NSAIDs increase the risk of cardiovascular disease and other health problems, but the exact cause has been unclear.
The UC Davis researchers compared naproxen, considered the safest over-the-counter NSAID, with a more potent anti-inflammatory, the prescription drug meclofenamate sodium (MS).
They found that MS increased reactive oxygen species, impaired mitochondrial function, decreased proteasome function, and increased cardiac cell death. Naproxen did not affect proteasome function or cause heart cells to die, but it did impair mitochondrial function and increase reactive oxygen species produced in cardiac cells.
“We were surprised to see that many of the NSAIDs we tested were causing the cardiac cell to die when used for prolonged periods,” said Gomes. “Some people are taking these drugs too often, and this is a problem. These drugs are abused.”
For moderate pain, Gomes suggests rubbing an anti-inflammatory topically onto the pained area, which would not expose the entire body to the drug. Taking an antioxidant like vitamin C before ingesting a NSAID may also reduce cardiac cell death.
Last year the U.S. Food and Drug Administration ordered warning labels for all NSAIDs to be strengthened to indicate they increase the risk of a fatal heart attack or stroke. The agency said studies have shown the risk of serious side effects can occur in the first few weeks of using NSAIDs and could increase the longer people use the drugs. The revised warning does not apply to aspirin.
The FDA said people who have a history of heart disease, particularly those who recently had a heart attack or cardiac bypass surgery, are at the greatest risk. But the risk is also present for people who don't have heart problems.
“Everyone may be at risk – even people without an underlying risk for cardiovascular disease,” said Judy Racoosin, MD, deputy director of FDA’s Division of Anesthesia, Analgesia, and Addiction Products.
In a major study published recently in the European Heart Journal, a number of leading heart specialists warned that there is no "solid evidence" that NSAIDs are safe.
"When doctors issue prescriptions for NSAIDs, they must in each individual case carry out a thorough assessment of the risk of heart complications and bleeding. NSAIDs should only be sold over the counter when it comes with an adequate warning about the associated cardiovascular risks. In general, NSAIDs are not be used in patients who have or are at high-risk of cardiovascular diseases," said co-author Christian Torp-Pedersen, a professor in cardiology at Aalborg University in Denmark.