LOw-Dose RAbeprazole Therapy for Reducing Gastrointestinal Events in Patients with High Bleeding Risk (LORA-HBR): A Prospective, Multicenter, Interventional Study

Abstract

Background: The widespread use of antithrombotic therapies increases bleeding risk, particularly in patients with a high bleeding risk (HBR). Although proton pump inhibitors are recommended for lowering the risk of upper gastrointestinal (UGI) bleeding, the optimal agent and dosage remain uncertain. This study evaluated the efficacy and safety of low-dose rabeprazole (LORA, 5 mg) in reducing the incidence of GI-related adverse events in HBR patients receiving chronic antithrombotic therapy. Methods: This was a prospective, multicenter, interventional study that enrolled 909 South Korean patients receiving long-term antithrombotic therapy with HBR features including age >= 70 years, dual antiplatelet therapy, combined antithrombotic regimens, and prior GI bleeding. The primary endpoint was the incidence of significant GI events, including overt/occult bleeding and symptomatic peptic ulcer disease (PUD). Secondary endpoints included study drug discontinuation owing to GI adverse events, composite cardiovascular events, and all-cause mortality. Results: No patients had significant UGI bleeding or symptomatic PUD. The median adherence rate was 92.0% (interquartile range [IQR], 87.0-95.0). Drug discontinuation owing to GI symptoms occurred in 32 patients (3.52%) at a median of 81 days (IQR, 36-119 days). GI-related adverse events were reported in 3.96%, with diarrhea, epigastric discomfort, and constipation being the most common. Non-GI bleeding and cardiovascular composite events occurred in 0.33% (n = 3) each, with all-cause mortality at 0.55% (n = 5). Conclusions: Low-dose rabeprazole was associated with reduced GI complications in patients receiving chronic antithrombotic therapy, with a favorable safety profile and high adherence. Further studies with larger and broader populations are required to confirm these findings.