A comparison of the upper gastrointestinal mucosal effects of valdecoxib, naproxen and placebo in healthy elderly subjects.
BACKGROUND
In long-term outcomes studies, cyclooxygenase COX-2 specific inhibitors spare COX-1 at supratherapeutic doses and therefore demonstrate improved gastrointestinal safety over nonspecific nonsteroidal anti-inflammatory drugs (NSAIDs). However, in clinical practice, anti-inflammatory drugs are often used for short-term treatment of pain.


OBJECTIVE
To compare the short-term upper gastrointestinal mucosal effects of naproxen with the new COX-2 specific inhibitor, valdecoxib, or placebo, in elderly subjects.


METHODS
In this multicentre, double-blind, randomized, study, elderly subjects (65-76 years old), with a normal baseline esophagogastroduodenoscopy (EGD), received oral valdecoxib (a supratherapeutic 40 mg b.d. dosage, n = 62), naproxen (500 mg b.d., n = 62), or placebo (n = 62) for 6.5 days. Upper gastrointestinal mucosal injury was evaluated post-treatment by EGD (day 7).


RESULTS
Subjects receiving naproxen (11/60, 18%) had significantly more gastroduodenal ulcers post-treatment than those receiving placebo (2/61, 3%; P < 0.01) or valdecoxib (0/60, 0%; P < 0.001). A similar significant finding was observed for gastric ulcer rates. All treatments had similar adverse event rates and clinical laboratory findings.


CONCLUSIONS
Valdecoxib, even at supratherapeutic doses, was associated with an ulcer rate significantly lower than naproxen but similar to placebo in healthy elderly subjects, despite the short duration of therapy (6.5 days). Naproxen and valdecoxib were as well tolerated as placebo.
Goldstein
J L
JL
University of Illinois at Chicago, Chicago, IL 60612, USA. jlgoldst@uic.edu
Kivitz
A J
AJ
Verburg
K M
KM
Recker
D P
DP
Palmer
R C
RC
Kent
J D
JD
D000284:Administration, Oral; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D005767:Gastrointestinal Diseases / Q000139:chemically induced*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects; D007555:Isoxazoles / Q000008:administration & dosage / Q000009:adverse effects*; D009288:Naproxen / Q000008:administration & dosage / Q000009:adverse effects*; D010003:Osteoarthritis / Q000188:drug therapy; D010146:Pain / Q000188:drug therapy; D012307:Risk Factors; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects*; D000096926:Benzenesulfonamides
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007555:Isoxazoles; D009288:Naproxen; D013449:Sulfonamides; C406224:valdecoxib; D000096926:Benzenesulfonamides