December 22, 2004
The National Institutes of Health (NIH) this week stopped a large study that had been under way to test whether long-term use of the popular anti-inflammatory drugs Celebrex or naproxen help to prevent the onset of Alzheimer's disease. The suspension came after researchers noted that people taking naproxen, a popular over-the-counter pain reliever, had an increase in heart attacks and strokes.
The study, called the Alzheimer's Disease Anti-Inflammatory Trial, or ADAPT, involved men and women with a family history of the illness. None of the study participants, aged 70 and up, had any symptoms of memory loss or mental decline at the start of the trial, but all were considered to be at increased risk for Alzheimer's because they had a close family member with the disease. Some had been taking the common pain reliever naproxen (sold in pharmacies under the brand names Aleve, Naprosyn, and Anaprox). Others received celecoxib (a popular arthritis pain reliever sold as Celebrex) or a look-alike placebo pill. Neither the study participants nor their doctors knew who was taking which medication. The trial began in 2001, and participants had been taking one of these drugs for several years.
The study was suspended after researchers noticed that people taking naproxen were 50 percent more likely to have a heart attack and stroke than those taking a placebo. The numbers were small, but significant. Of the nearly 2,400 people enrolled, about 70 had a heart attack or stroke, with more problems occurring in the naproxen group. "This step is being taken as a precautionary measure to ensure the safety of the study's participants," said NIH Director Elias A. Zerhouni, M.D. "The investigators made their decision based on the risk-benefit analysis specific to this trial."
Another major factor in the trial suspension was a similar warning issued last week about heart problems due to Celebrex. High doses of the drug were found to increase the risk of heart attacks and strokes in a study testing the drug to prevent cancer. (A related drug, called Vioxx, was pulled from the market in late 2004 when similar concerns were raised about heart dangers.) In the current Alzheimer's study, however, Celebrex did not seem to increase heart problems. Still, researchers thought it prudent to withdraw use of that drug as well and discontinue the study.
Celebrex and Aleve are popular pain relievers commonly taken to relieve arthritis. Scientists were hopeful that these and related drugs, which work in part by reducing inflammation, may have beneficial effects on blood vessels throughout the body, including those that provide blood flow and nourishment to the brain. Inflammation in the brain is a hallmark of Alzheimer's, but whether it is a cause or effect of the disease remains unknown.
Aleve belongs to a class of medications known as non-steroidal anti-inflammatory drugs, or NSAIDs. There are many other NSAIDs as well, such as ibuprofen and indomethacin . Aspirin also has anti-inflammatory effects. Celebrex is known as a COX-2 inhibitor. Some earlier research suggested that taking these or related drugs may help to prevent the onset of Alzheimer's. However, other studies have suggested that NSAIDs, COX-2s, and other anti-inflammatories do little to stop the development of Alzheimer's. The current large NIH study aimed to test whether long-term use of these medicines has benefits for those concerned about Alzheimer's.
Researchers agree that much of the current news about the possible dangers of inflammation-fighting drugs remains confusing. Most of these drugs have been used safely for many years, without apparent harm to the heart, though there have always been risks of gastric ulcer. Experts will be conducting additional studies and recommend that anyone taking these medicines follow directions closely and consult their doctors, especially if they were taking an anti-inflammatory over long periods.
Use of Non-Steroidal Anti-Inflammatory Drugs Suspended in Large Alzheimer's Disease Prevention Trial. National Institutes of Health.