Pharmacological safety and real-world efficacy of the potassium-competitive acid blocker fexuprazan in cardiovascular patients receiving antithrombotic therapy: a prospective cohort study (FEXGARD)

Background and Aims Gastroesophageal reflux disease (GERD) is common in patients with CVD receiving long-term antithrombotic therapy, increasing gastrointestinal (GI) bleeding risk. Potassium-competitive acid blockers, such as fexuprazan, provide rapid and potent acid suppression; however, relevant evidence in this high-risk population is limited. This study evaluated the effects of fexuprazan on fasting serum gastrin levels, GERD symptoms, and bleeding outcomes in patients with CVD receiving antithrombotic agents. Methods In this prospective observational study conducted at a tertiary hospital, 400 patients receiving antiplatelet or anticoagulant therapy were administered fexuprazan. Fasting venous blood samples were collected at baseline and 6 months, and total serum gastrin levels were measured. GERD symptoms were assessed using the Frequency Scale for the Symptoms of GERD (FSSG). Secondary outcomes, including GI bleeding, other-site bleeding, and mortality, were recorded over 12 months. Subgroup analyses were performed according to antithrombotic regimen and age. Results Fexuprazan significantly increased fasting serum gastrin (152.1 ± 215.9 vs. 249.1 ± 210.3 pg/mL; p < 0.001) and improved FSSG total scores (16.3 ± 5.0 vs. 15.0 ± 6.0; p < 0.001). During the 12 months, two GI bleeding events (0.5%), 11 other-site bleeding events (2.8%), and no deaths occurred. Subgroup analyses revealed no significant differences between users of antiplatelet agents, warfarin, and non-vitamin K antagonist oral anticoagulants (NOACs). However, bleeding events occurred only in the NOAC group. Patients aged 70 years or older had a greater increase in gastrin than younger patients (+118.4 vs. +64.3 pg/mL; p = 0.025). Conclusion Fexuprazan increased gastrin levels and improved GERD symptoms with few bleeding events in patients with CVD receiving antithrombotic therapy. This study provides clinical data on the safety and tolerability of fexuprazan in a high-risk cardiovascular population under long-term antithrombotic therapy. Elderly patients exhibited a greater increase in gastrin levels, warranting closer monitoring and further investigation.