Assessing the Risk of Gastrointestinal Bleeding with Concomitant Antiplatelet Therapy: Analysis of Spontaneous Adverse Event Database

Abstract

Gastrointestinal bleeding induced by dual antiplatelet therapy (DAPT) with aspirin and P2Y12 inhibitor is known to have an impact on patient prognosis. However, few studies have evaluated the increased risk of gastrointestinal bleeding with DAPT and the timing of its occurrence by bleeding site. We evaluated the trends of increased risk and timing of concomitant bleeding using the Japanese Adverse Drug Event Report, a database of adverse event reports in Japan. Cases of upper gastrointestinal bleeding and lower gastrointestinal bleeding were selected from this database and divided into single agent and combination groups according to the use of aspirin or P2Y12 inhibitors. The adjusted reporting odds ratios calculated in each group for concomitant aspirin or P2Y12 inhibitor use were compared. The number of days to bleeding was calculated from the date of drug initiation and the date of bleeding onset, and the pattern of onset was determined from the distribution. Adjusted reporting odds ratios suggested that the combination of aspirin and a P2Y12 inhibitor may increase the risk of upper gastrointestinal bleeding. Weibull distribution parameters suggested that upper gastrointestinal bleeding and lower gastrointestinal bleeding may have different expression trends with the combination of aspirin and P2Y12 inhibitors. These results suggest that it is important for pharmacists to pay more attention to the occurrence of upper gastrointestinal bleeding during DAPT use compared with antiplatelet monotherapy, and to recognize and systematically monitor the trend of occurrence.