Lower GI bleeding risk of nonsteroidal anti-inflammatory drugs and antiplatelet drug use alone and the effect of combined therapy

Background The effect of a combined antithrombotic drug regimen on lower GI bleeding (LGIB) remains unknown. Objective To investigate the risk of LGIB associated with nonsteroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin, thienopyridine (ticlopidine or clopidogrel), or other antiplatelets used. Design Prospective study. Setting Emergency hospital, gastroenterology department. Patients A cohort of 319 patients emergently hospitalized for acute, continuous, or frequent LGIB and 3358 patients with no bleeding on colonoscopy. Main Outcome Measurements Odds ratios (ORs) for the risk of LGIB associated with drug exposure adjusting for age, sex, smoking, alcohol, medications, comorbidities, and GI symptom scores. Results After considering antithrombotic drugs by dividing them into single- and combined-use, single use of nonselective NSAID or cyclooxygenase-2 inhibitor was independently associated with LGIB. The combined use of NSAIDs with low-dose aspirin (OR 4.3) or with other antiplatelets (OR 4.9) was more associated with LGIB than the use of NSAIDs alone (OR 2.3). Use of low-dose aspirin, thienopyridine, or other antiplatelets alone was not significantly associated with LGIB, but combined use of low-dose aspirin with thienopyridine (OR 2.2) or with other antiplatelets (OR 3.6) was associated with LGIB. Combined use of different NSAIDs carried a higher risk than single use (combined use, OR 4.9; single use, OR 2.3). Limitations Single-center study. Conclusion The use of nonselective or selective NSAIDs alone was associated with LGIB. Although antiplatelet use alone was not significantly associated with LGIB, combined use of NSAIDs with antiplatelets or of low-dose aspirin with thienopyridine or with nonthienopyridine antiplatelets was independently associated with LGIB.