The Medical Minute: Concerns surrounding Vioxx

November 11, 2004

By John Messmer
Penn State Milton S. Hershey Medical Center
Penn State College of Medicine

Vioxx was the subject of the latest flap about prescription drugs. It affected millions of people in the United States and stands to keep lawyers busy for years to come. It has prompted calls for the Food and Drug Administration (FDA) to raise standards of evidence in the drug-approval process and questions about the relationship between researchers and pharmaceutical developers. The issue is complicated, but a big question for the consumer is what to do about Vioxx and others in its class. Vioxx is off the market now, but similar drugs remain. If you took Vioxx, you may wonder if you will get heart disease later or if other pain medications will do the same thing.

To fully understand the issue, a little bit of technical background is needed. Much of the pain we experience is due to a process called inflammation. Inflammation helps us heal injuries by clearing damaged tissue, preventing bleeding and increasing blood flow to the injured area so more oxygen and nutrients are provided for tissue growth. Inflammation hurts; if it did not, we would never realize when we have a cut or bruise and would not avoid potentially serious injuries and infection. Sometimes, inflammation comes from wear-and-tear on our joints as in tendonitis or bursitis and osteoarthritis. Occasionally, inflammation improperly attacks our tissues when there's no reason, as with rheumatoid arthritis.

Inflammation is a complicated chemical process, but there are two key parts of the reaction: thromboxane and prostacyclin. Thromboxane helps platelets stick together and makes blood vessels constrict. Prostacyclin opens blood vessels to keep blood flowing. These chemicals are produced by an enzyme called cyclooxygenase or COX. There are two main forms, COX1 and COX2, that are found in blood vessels, platelets and other areas. In pain, COX2 is the main enzyme, not COX1 that has a part in protecting the stomach from ulcers and helping platelets to form blood clots.

Traditionally, pain and inflammation were treated with aspirin or the steroid cortisone; both inhibit COX1 and COX2. They are great for pain and inflammation because they inhibit COX2, but by inhibiting COX1 in the stomach, there was a risk of stomach ulcers and of severe bleeding because platelets were inhibited. In the 1960s anti-inflammatory drugs unrelated to steroids called nonsteroidal anti-inflammatories (NSAIDs) were developed to avoid some of the adverse effects of aspirin and steroids. These, too, inhibited COX1 and COX2 allowing stomach ulcers to develop.

In the 1990s, a new class of anti-inflammatories was developed. This group selectively inhibited COX2 with little or no effect on COX1. They had the advantage of inhibiting the chemical reaction in inflammation but without interfering with the protective effects on the stomach from COX1. Studies showed a significant reduction in the risk of stomach ulcers when people used one of the selective COX2 inhibitors. Because they did not inhibit platelets, they could be used for surgical pain. These drugs have also come to be known as "coxibs" from the chemical name for Vioxx (rofecoxib), Celebrex (celecoxib) and Bextra (valdecoxib).

Inside arteries the COX enzyme produces prostacyclin to help keep the artery open and blood flowing to the organs. Originally, it was thought that only COX1 was in arteries, and that coxibs would not affect them. Later it was realized COX2 is the main COX enzyme there. A drug that only inhibits only COX2 could cause arteries to narrow. If that occurs in the heart and a clot forms, there could be a heart attack.

The important point is that coxibs do not cause heart attacks; rather they increase the likelihood of one happening, but it may take months for the risk to increase. The risk goes away very quickly, probably in a day or two after stopping the drug. While it is not known conclusively, many doctors think the danger is only in people already at risk for heart disease: those who smoke or have high blood pressure, diabetes or high cholesterol.

So, what's the alternative? Doctors and patients must consider the relative risks. Other NSAIDs do not seem to increase the risk of heart attack, but do increase the risk of stomach ulcers, and they can raise blood pressure and affect kidney function (as can coxibs). NSAIDs include ibuprofen (Advil and Motrin IB), naproxen (Aleve), ketoprofen (Orudis KT) and others available only by prescription. For most people, short-term use of a coxib or regular NSAID is safe. For prolonged use, discuss your individual risks with your doctor. No medication is perfectly safe, but with knowledge, risks can be reduced.

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Last Updated March 19, 2009