Meta-analysis of randomized controlled studies and case-control studies showed that the risk of low-dose aspirin for upper gastrointestinal bleeding was 1.6-8.2. Some reports showed that the risk of upper gastrointestinal bleeding (UGIB) was high in patients receiving ticlopidine or clopidogrel. A meta-analysis study reported that data regarding the risk for GI bleeding of new direct oral anticoagulants (apixaban, dabigatran and rivaroxaban) were inconclusive. Proton-pump inhibitor and histamine 2-recetor antagonist were effective for prevention of upper GI mucosal injury in patients receiving low-dose aspirin. Some case-control studies showed that PPI use significantly reduced the risk of UGIB in patients with receiving clopidogrel, but not in those with receiving warfarin.