11/10/97
Contact: Jody Sumrall, (650) 723-7897 or 723-6911, e-mail: [email protected]
Aspirin and its cousins ranked by stomach toxicity; simple test predicts patient risk
STANFORD -- Stomach bleeding is a well-known side effect of nonsteroidal anti-inflammatory drugs (NSAIDs), the most commonly used drugs in the world. Researchers at Stanford University have now ranked the risk of stomach bleeding for each of 16 different NSAIDs, including the nonprescription drugs aspirin, ibuprofen, ketoprofen and naproxen.
The researchers have also devised a simple questionnaire for predicting the risk of stomach damage in individuals who are considering chronic use of NSAIDs.
Together, the drug toxicity rankings and the patient questionnaire can help physicians select a drug and dosage level that is safest for each patient, said Dr. Gurkirpal Singh, a clinical assistant professor of medicine (immunology and rheumatology) and senior research scholar at Stanford University School of Medicine.
"We want to provide people with a rational way to decide what NSAID to use," Singh said.
Singh presented the results of the federally funded work Sunday, Nov. 9, and Wednesday, Noc. 12, at the annual meeting of the American College of Rheumatology, held in Washington, D.C.
Every day, NSAIDs are taken by more than 30 million people around the world. The nonprescription NSAIDs are used for any number of aches and pains, while a plethora of prescription-only NSAIDs are used for conditions such as arthritis.
All of the currently available NSAIDs have roughly equivalent pain-relieving effects, and all can cause some degree of stomach damage. In its early stages this problem is undetectable, but the onset of a major stomach bleed can be sudden and can require transfusions and surgery, noted Singh. More than 107,000 people are hospitalized every year in the United States for NSAID-related stomach bleeds and other complications, and 12 to 15 percent of those patients die from the bleeds, he said.
To come up with the drug rankings, Singh and his colleagues analyzed results from more than 9,000 NSAID treatment courses in nearly 4,000 rheumatoid arthritis patients from all over North America. They used the data to group 16 commonly used NSAIDs into categories of low, medium and high risk.
All four of the nonprescription NSAIDs had similar toxicity ratings and fell into the medium-risk group, the researchers found. (See specific rankings below.)
The differing risks among the 16 drugs may be explained by the drugs' interactions with proteins called cyclooxygenase 1 and 2 (COX-1 and COX-2), Singh said. When the drugs turn off COX-2, they turn off inflammation; but shutting down the similar COX-1 causes problems in the stomach lining. Singh found that the high-risk NSAIDs were those that significantly inhibit COX-1 and so are less selective for COX-2.
New NSAIDs not yet on the market should be far more selective for COX-2 and may provide a better level of safety, he said.
The questionnaire developed by Singh and his colleagues can be used along with the toxicity rankings to help physicians select appropriate drugs for individual patients. For those deemed at high risk of a stomach bleed, doctors may wish to prescribe non-NSAID drugs such as acetominophen or tramadol, or to recommend an NSAID along with the stomach-protecting drug misoprostol, Singh said.
The questionnaire, called the Stanford Calculator of Risk for Events (SCORE), is the first simple and accurate predictor of the risk that a given patient will suffer a bleed, Singh said.
"It [the risk of stomach bleeding] isn't like hypertension, where you can measure blood pressure," he said. "With existing clinical and laboratory tests, we just can't tell who is going to bleed. The only way to tell is with this new questionnaire."
The five-item questionnaire covers a patient's age, self- assessment of health status, time using the steroid drug prednisone, previous hospitalizations for stomach bleeds, and other previous side effects from NSAID usage. Singh found that predictions from the SCORE test closely matched the actual hospitalization risks for 3,683 rheumatoid arthritis patients from all over North America.
He has devised a simple paper version of the test, as well as a computer program that also compares a patient's chances of suffering a bleed with more familiar risks, such as catching a cold, to help people put their bleeding risk in perspective. Singh envisions patients completing either questionnaire while sitting in physicians' waiting rooms.
Both the NSAID toxicity research and the SCORE work were funded by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
The toxicity rankings were developed at Stanford by Singh, research scholar Richard Terry (now deceased), senior research analyst Dena Ramey, professor of medicine (immunology and rheumatology) Dr. James Fries, associate professor of medicine (gastroenterology) Dr. George Triadafilopoulos, senior research scientist Jerry Halpern, and professor of health research and policy Dr. Byron Brown.
The SCORE questionnaire was formulated and tested by Singh, Terry, Ramey, Triadafilopoulos, Brown and senior research analyst Raymond Balise.
STOMACH TOXICITY OF NSAIDS
(Drugs listed by generic name)
Lowest Risk
nabumetone etodolac salsalate sulindac
Medium Risk
diclofenac *ibuprofen *ketoprofen *aspirin *naproxen tolmetin
Highest Risk
flurbiprofen piroxicam fenoprofen indomethacin meclofenamate
* Available without prescription
List adapted from data presented 11/9/97 to the American College of Rheumatology by Stanford researcher Dr. Gurkirpal Singh. Clinical and epidemiological research data such as these have important statistical considerations. Please contact Dr. Singh (650-723-9646) for further details about the study.
--ww--
RSS