AGE LR�ve LR–vePrevalence variationwith ASGE criteria

Prevalence variationwithout ASGE

criteria

� 60 yrs 1.25 .61 25%329% 25%317%� 60 yrs 1.17 .76 33%337% 33%328%

Conclusions: The use of appropriate indications can improve patientsselection for Colonoscopy; however the predictive value of ASGE criteriais relatively low in the class of age � 60 yrs, and slightly higher in the classof age �� 60 yrs. We observed a significant reduction of the prevalenceof relevant endoscopic lesions only in the case of indication which is notincluded among ASGE criteria.

717

GASTROINTESTINAL TOLERABILITY AMONGOSTEOARTHRITIS PATIENTS RECEIVING LOW DOSEASPIRIN IN COMBINATION WITH ROFECOXIB ORNAPROXENGregory P. Geba, M.D.*, Adam B. Polis, M.A., Carol S. Skalky, B.A.,Richard A. Petruschke, Pharm.D. and Thomas W. Dobbins, Ph.D.Clinical Development, Merck & Co., Inc., West Point, PA.

Purpose: Gastrointestinal adverse experiences (AEs) and perforations,ulcers, and bleeding (PUBs) were evaluated in a subgroup of rofecoxib(ROF) and naproxen (NAP) patients receiving concomitant low dose as-pirin in the ADVANTAGE trial.Methods: 5557 osteoarthritis patients were randomized to ROF 25 mg/d(N�2785) or NAP 500 mg bid (N�2772) for 3 months, including 719(13%) low–dose (100 mg/d) aspirin users (ROF, 352; NAP, 367) andassessed at baseline, Weeks 6, and 12. Primary endpoint was GI tolerabilitydefined by incidence of discontinuations due to GI AEs. Cumulativeincidence was calculated by Kaplan–Meier estimates, relative risk (RR)and test of treatment by aspirin interaction by Cox proportional hazardsmodel, and treatment group comparisons by log–rank test. Incidence ofPUBs (gastroduodenal perforations, gastric outlet obstruction, symptomaticgastroduodenal ulceration, and GI bleeds) was also reported. Independentadjudication committee confirmed all GI AEs included in this analysis andPUBs, initially reported as unconfirmed.Results: Among low dose aspirin users, 17 (5.2%) ROF and 31 (9.4%)NAP patients [RR�0.56 (CI: 0.31, 1.01)] discontinued due to GI AEs,similar to the overall cohort incidence [rofecoxib, 5.9%; naproxen, 8.1%,RR�0.74 (CI: 0.60, 0.92, p�0.005)]. Interaction between treatment andaspirin use was not significant (p�0.378), indicating that irrespective ofaspirin use, ROF was associated with reduced risk of GI AEs. PUBs werereported in six (0.2%) ROF and 12 (0.4%) NAP patients, of which two(0.1%) ROF and nine (0.3%) NAP patient events were confirmed. Amonglow dose aspirin users, there was only one confirmed and unconfirmed PUBreported in each treatment group. There was a higher incidence of GI AEswith NAP compared to ROF in the total cohort (26.0% NAP, 24.1% ROF),and among low dose aspirin users (29.8% NAP, 22.0% ROF).Conclusions: Although not powered to be conclusive, this subgroup anal-ysis suggests that improved GI tolerability with ROF relative to NAPappears to be maintained in the cohort of patients receiving low doseaspirin for cardiovascular prophylaxis. Fewer GI AEs and discontinuationsdue to GI AEs were observed among ROF than NAP patients in the overalland low dose aspirin user populations.

718

THE EFFECTIVENESS OF PROTON PUMP INHIBITORS INNONEROSIVE GERDBonnie Dean, Ph.D., Anacleto Gano, M.P.H., Joshua Ofman, M.D. andRonnie Fass, M.D.*. Zynx Health, Inc., Los Angeles, CA; Departmentsof Medicine and Health Services Research, Cedars–Sinai MedicalCenter, Los Angeles, CA and Southern Arizona Health Care System,Tucson, AZ.

Purpose: Nonerosive reflux disease (NERD) is the most common form ofGERD, occurring in 50%–70% of patients evaluated. Yet, most dataregarding response to PPI therapy are from studies in erosive esophagitis.We sought to isolate the studies of NERD, to determine more preciseestimates of the effectiveness of PPIs for heartburn control.Methods: We searched the MEDLINE, HEALTHSTAR, and EMBASEbibliographic databases from 1985 to the present and FDA submissions toidentify randomized clinical trials evaluating the effectiveness of PPItherapy for heartburn resolution in NERD. Articles were included in thereview if they evaluated PPI treatment of endoscopically confirmed NERD(Grade 0, or grade 1–erythema/friability without erosions) and they mea-sured heartburn resolution using intention to treat analysis. Estimates of4–week heartburn resolution were calculated for satisfactory (less than oneday of moderate heartburn during the last 7 days of treatment) and completeheartburn control (no heartburn during the last 7 days of treatment) usingpooled data.Results: A total of 1170 articles were reviewed. After exclusion criteriawere applied, 6 articles and 4 FDA–reports were included. Six studies eachevaluated 4–week satisfactory control and complete control. At 4 weeks,PPI therapy resulted in satisfactory resolution among 57% and completeresolution among 37% of all patients. PPI therapy was significantly moreeffective than placebo for satisfactory and complete heartburn control.Compared to placebo, PPIs were more effective for complete than satis-factory heartburn control. The pooled PPI response rate is greatest inpatients with grade 0, and the relative risk for complete response rangesfrom 2.9 in grade 0 to 7.9 in the combined group of grade 0–1.Conclusions: PPI therapy is highly effective in reducing and resolvingheartburn among patients with NERD, however, the response rates arelower than typically reported for erosive esophagitis. The greater benefitachieved in NERD patients including grade 1 without erosions, suggeststhat the erythema and friability may be a form of erosive disease rather thanpart of NERD.

Pooled Estimates of Satisfactory and Complete Heartburn Resolution at 4 Weeks

Responserate for

satisfactorycontrol for

placebo(N)

Responserate for

satisfactorycontrol fortreatment

(N)

RR(95% CI) forsatisfactory

control

Responserate for

completecontrol for

placebo(N)

Responserate for

completecontrol fortreatment

(N)

RR(95% CI) for

completecontrol

All studies 22.9% (370) 56.6% (1236) 2.5 (2.0, 3.0) 9.6% (576) 36.6% (1278) 3.8 (3.0, 5.0)Grade 0

(negativeendoscopy)

20.3% (264) 59.7% (565) 2.9 (2.3, 3.8) 13.0% (347) 37.4% (879) 2.9 (2.2, 3.8)

Grade 0 and1 (noerosions)

29.2% (106) 54.0% (671) 1.9 (1.4, 2.5) 4.4% (229) 35.0% (399) 7.9 (4.3, 14.6)

719

COMPARISON OF OMEPRAZOLE TO PLACEBO IN 24 HOURPREVENTION OF FREQUENT HEARTBURNMervyn Danilewitz, M.D., FACG, Lisa Allgood, M.Sc., Michael Shaw,M.D. and David Peura, M.D., FACG*. AstraZeneca LP, Chesterbrook,PA; Procter & Gamble Health Sciences Institute, Cincinnati, OH; St.Louis Park, MN and University of Virginia, Charlottesville, VA.

Purpose: Two trials investigated the effectiveness of omeprazole magne-sium (Ome–Mg) in preventing frequent heartburn (2 or more days/wk). Theprimary objective was to demonstrate that a single dose of Ome–Mgcompletely prevents heartburn symptoms for 24 hours.Methods: Over 3120 subjects were randomized to 10 mg Ome–Mg, 20 mgOme–Mg or placebo in multicenter, double blind, double dummy, placebocontrolled, parallel studies with a 1–week placebo run–in phase to assessthe heartburn frequency. Eligible subjects were randomized into a 2–weekdouble–blind phase, where single doses of Ome–Mg 20, Ome–Mg 10, orplacebo were taken every morning. Analyses tested the effectiveness ofOme–Mg in preventing heartburn over 24 hours on Day 1 (following thefirst dose) and on the percentage of days during the 2–week use periodwhen a subject was without heartburn (evaluated on Day 14). The effect onnocturnal heartburn was also assessed.

S235AJG – September, Suppl., 2002 Abstracts