Antiplatelet therapy with or without PPIs for the secondary prevention of cardiovascular diseases in patients at high risk of upper gastrointestinal bleeding: A systematic review and meta-analysis

Recurrent upper gastrointestinal (UGI) and cardiovascular (CV) events of the three antiplatelet therapies in patients with cardiovascular diseases (CVD) were compared. Studies published in the PubMed, Embase, and Cochrane Central Register of Controlled Trials electronic databases that compared differences in adverse outcomes associated with the three antiplatelet therapies were reviewed. Five studies with a total number of 7,399 patients were included. No significant differences were found in the incidence of recurrent UGI events among the three antiplatelet therapies. However, in the aspirin-induced ulcer bleeding subgroups, aspirin plus proton pump inhibitors (PPIs) was associated with a significantly lower risk of recurrent UGI events (OR: 0.06, 95% CI: 0.01-0.32; z=3.30 and P=0.001) and UGI bleeding (OR: 0.06, 95% CI: 0.01-0.34; z=3.24 and P=0.001) compared to clopidogrel alone. Both aspirin plus PPIs (OR: 2.12, 95% CI: 1.58-2.84; z=5.00 and P<0.01) and clopidogrel plus PPIs (OR: 2.57, 95% CI: 1.89-3.51; z=5.97 and P<0.01) were related to a comparatively higher risk of recurrent CV events when compared to clopidogrel alone. In patients at high UGI bleeding risk (regardless of whether it was aspirin-induced) and under treatment of single antiplatelet therapy, aspirin plus PPIs should be considered as the first choice for UGI protection rather than clopidogrel alone and clopidogrel plus PPIs. However, in terms of CV protection, clopidogrel alone appears to be superior in reducing CV risk, while clopidogrel plus PPIs may relate to an increased CV risk due to the potential drug-drug interaction.