Reduced incidence of upper gastrointestinal ulcer complications with the COX-2 selective inhibitor, valdecoxib.
OBJECTIVE
In a predefined analysis, data were pooled from eight blinded, randomized, controlled trials, and separately from three long-term, open-label trials to determine the rate of upper gastrointestinal ulcer complications with the cyclo-oxygenase-2 selective inhibitor, valdecoxib, vs. non-selective non-steroidal anti-inflammatory drugs.


METHODS
In randomized, controlled trials, 7434 osteoarthritis and rheumatoid arthritis patients received placebo (n = 973), valdecoxib 5-80 mg daily (n = 4362), or a non-selective non-steroidal anti-inflammatory drug (naproxen, ibuprofen or diclofenac; n = 2099) for 12-26 weeks. In long-term, open-label trials, 2871 patients received valdecoxib 10-80 mg daily for up to 1 year. All potential events were reviewed by a blinded, independent review committee based on a priori definitions of ulcer complications (perforations, obstructions, bleeds).


RESULTS
In randomized, controlled trials, 19 of 955 potential events were adjudicated to be ulcer complications. Valdecoxib was associated with a significantly lower ulcer complication rate than non-selective non-steroidal anti-inflammatory drugs (0.68% vs. 1.96%, all patients; 0.29% vs. 2.08%, non-aspirin users; P < 0.05). In long-term, open-label trials, seven of 310 potential events were adjudicated to be ulcer complications; the annualized incidence for valdecoxib was 0.39% (seven of 1791 patient-years) for all patients and 0.2% (three of 1472 patient-years) for non-aspirin users.


CONCLUSIONS
Valdecoxib, including above recommended doses, is associated with a significantly lower rate of upper gastrointestinal ulcer complications than therapeutic doses of non-selective non-steroidal anti-inflammatory drugs.
Goldstein
J L
JL
University of Illinois at Chicago, Chicago, IL 60612, USA. jlgoldst@uic.edu
Eisen
G M
GM
Agrawal
N
N
Stenson
W F
WF
Kent
J D
JD
Verburg
K M
KM
D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007555:Isoxazoles / Q000009:adverse effects*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D010003:Osteoarthritis / Q000188:drug therapy; D010437:Peptic Ulcer / Q000139:chemically induced*; D011451:Prostaglandin-Endoperoxide Synthases; D016032:Randomized Controlled Trials as Topic; D013449:Sulfonamides / Q000009:adverse effects*; D000096926:Benzenesulfonamides
D000894:Anti-Inflammatory Agents, Non-Steroidal; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D007555:Isoxazoles; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D013449:Sulfonamides; C406224:valdecoxib; D000096926:Benzenesulfonamides; C496540:PTGS2 protein, human