Risk factors for NSAID-associated upper GI clinical events in a long-term prospective study of 34 701 arthritis patients.
BACKGROUND
Nonsteroidal anti-inflammatory drugs (NSAID)-related GI effects vary based on patient characteristics.


OBJECTIVE
To assess risk factors for NSAID-associated upper GI clinical events and dyspepsia.


METHODS
Patients ≥50 years with osteoarthritis or rheumatoid arthritis were randomized to etoricoxib or diclofenac in a prespecified intent-to-treat analysis of three double-blind randomized trials. Potential risk factors for upper GI clinical events (bleeding, perforation, obstruction, or ulcer), complicated events (perforation, obstruction, bleeding) and discontinuations due to dyspepsia were assessed with Cox proportional hazard models.


RESULTS
Significant predictors of clinical events and complicated events included age ≥65 years [hazards ratios (HRs) = 2.25 (1.84-2.76), 4.09 (2.82-5.92)], prior event [HRs = 2.57 (1.94-3.39), 3.23 (2.09-5.00)], low-dose aspirin [HRs = 2.34 (1.87-2.92), 3.41 (2.33-5.00)] and corticosteroid [HRs = 1.85 (1.41-2.43), 2.09 (1.29-3.38)]. Predictors of discontinuation due to dyspepsia included prior dyspepsia [HR = 1.78 (1.44-2.00)], prior event [HR = 1.78 (1.40-2.27)] and age ≥65 years [HR = 1.35 (1.16-1.57)].


CONCLUSIONS
Assessment for age ≥65 years, prior upper GI clinical events and low-dose aspirin use are key in identifying patients who should either avoid NSAIDs or employ management strategies to reduce NSAID-associated upper GI events. Prior dyspepsia or upper GI clinical events and age ≥65 years also predict an increased risk of developing dyspepsia severe enough to necessitate discontinuation of NSAIDs.
University of Southern California, Los Angeles, CA 90033, USA. llaine@usc.edu
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Laine
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Curtis
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Cryer
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Kaur
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Cannon
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001168:Arthritis / Q000188:drug therapy*; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects*; D004008:Diclofenac / Q000009:adverse effects*; D000077613:Etoricoxib; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011725:Pyridines / Q000009:adverse effects*; D012307:Risk Factors; D013450:Sulfones / Q000009:adverse effects*; D013997:Time Factors; D041742:Upper Gastrointestinal Tract / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D011725:Pyridines; D013450:Sulfones; D004008:Diclofenac; D000077613:Etoricoxib