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There are at least two cyclooxygenase ("COX") enzymes within the body:

  • The COX-1 enzyme releases prostaglandins (fatty acid molecules) that help to form a protective coating within the digestive tract, and
  • The COX-2 enzyme releases prostaglandins responsible for pain and inflammation.

Traditional NSAIDs inhibit both enzymes. They provide both pain relief and anti-inflammatory benefit. However, because inhibition of COX-1 leaves the stomach lining vulnerable to injury, such NSAIDs may promote side effects such as stomach ulcers and bleeding. If you do take one of these medicines, your doctor may also want you to take a stomach acid blocker, such as a proton pump inhibitor, to lower the risk. By contrast, inhibition of only COX-2 provides pain relief but is less likely to cause stomach ulcers or bleeding.

COX-2 inhibitors are a relatively new class of medications that were developed to manage the pain and inflammation of arthritis without the negative side effects of NSAIDs. These medicines have been very controversial since 2004, when rofecoxib (Vioxx), once presumed safe, was withdrawn from the market because of increased danger of heart attack and stroke. Similar concerns were then raised about valdecoxib (Bextra), celecoxib (Celebrex), and now even ibuprofen and other traditional NSAIDs (except for aspirin). Bextra has also been removed from the market. Just one of the COX-2 inhibitors, Celebrex , is approved by the U.S. Food and Drug Administration (FDA) and is available by prescription. COX-2 inhibitors may also impair kidney function, particularly in the elderly. They also may increase blood pressure. For these reasons, anyone with a history of heart disease, high blood pressure, stroke, or transient ischemic attack (TIA) should not take COX-2 inhibitors without specific instruction from their health care provider. You also should not take COX-2 inhibitors if you are pregnant or trying to become pregnant.

A growing body of evidence suggests that the heart risks are real and important to consider, making it wise to weigh the risks versus the benefits when taking NSAIDs, especially if you are at risk for heart disease. COX-2 inhibitors may elevate heart and stroke risks at any dose. The non-selective NSAIDs (except for aspirin) appear to increase risk, but only at higher doses. If someone at risk for cardiovascular disease uses these traditional NSAIDs, the medicines should be used at the lowest effective dose, for the shortest necessary time, and perhaps along with low-dose aspirin and a proton pump inhibitor to reduce side effects.

Review Date: 12/24/2012

Reviewed By: Ariel D. Teitel, MD, MBA, Clinical Associate Professor of Medicine, Division of Rheumatology, NYU Langone Medical Center. Review provided by VeriMed Healthcare Network.

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