Just days after the National Institutes of Health (NIH) announced the suspension of a cancer-prevention trial because of a heightened risk for cardiovascular (CV) events among patients taking elevated doses of celecoxib (Celebrex®), federal health officials have halted an NIH Alzheimerâ„¢s disease prevention study of over-the-counter (OTC) naproxen (Aleve®, Bayer) and celecoxib following the release of data showing that patients taking naproxen had a 50% higher incidence of heart attack and stroke.1 The NIH study, however, did not show an increase in CV risk among celecoxib patients.
Researchers at the NIH National Institute on Aging (NIA) uncovered the higher rate of CV events from a data review of the ongoing, 3-year Alzheimer's Disease Anti-Inflammatory Prevention Trial (ADAPT). According to the NIA, epidemiologic studies have suggested an association between the use of nonsteroidal antiinflammatory drugs and decreased risk of Alzheimer's disease.2
At a December 20th news conference, Sandra Kweder, MD, of the US Food and Drug Administration, said the NIH study is the first to show that naproxen may increase the risk of heart attack or stroke and that the findings are Å“confusing. Dr. Kweder noted that the agency would not initiate any immediate regulatory action regarding naproxen. We are not contemplating any specific regulatory action over the next few days, Dr. Kweder said. We will be working with the NIH to try to understand the data better and determine what will be appropriate from there.
At the present time, health officials are advising patients not to exceed the recommended dose of OTC naproxen 200 mg twice daily or continue therapy for more than 10 days unless authorized by a physician.
Approximately 2500 patients aged 70 years or older who had a family history of Alzheimer's disease were randomly assigned to receive either naproxen 220 mg twice daily, the cyclooxygenase-2 inhibitor celecoxib 200 mg twice daily, or placebo. ADAPT investigator, John Breitner, MD, of the Veterans Affairs Medical Facility and the University of Washington, in Seattle, Washington, reported that about 70 patients of the 2500 suffered stroke or heart attack, 23 of whom died.
Pfizer Inc, manufacturer of celecoxib, announced on December 17th that a National Cancer Institute-sponsored cancer-prevention trial showed at least a 2.5-fold increased risk of fatal and nonfatal CV events compared with placebo.
The findings emerged from an analysis of the long-term Adenoma Prevention with Celecoxib (APC) trial, in which patients received 400 mg to 800 mg of celecoxib daily, 2 to 4 times higher than the dose recommended for the management of arthritis.
References:
- National Institutes of Health. Use of non-steroidal anti-inflammatory drugs suspended in large Alzheimer's disease prevention trial. Available at: http://www.nih.gov/news/pr/dec2004/od-20.htm . Accessed December 22, 2004.
- National Institute on Aging. Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT) Launched. Available at: http://www.alzheimers.org/nianews/nianews37.html . Accessed December 22, 2004.