Potassium-Competitive Acid Blocker Versus pROton-Pump Inhibitor for GastroproTECTion Strategies In Patients at High Gastro-Intestinal Bleeding Risk Receiving Antithrombotic Therapy

Inclusion Criteria:

1. Patients 19 years of age or older with known cardiac and vascular disease who arereceiving chronic use of antithrombotic drugs (either antiplatelets, oralanticoagulant (OAC), and its combinations). Specific clinical conditions that mayconfer a need for long-term antithrombotic therapy may include documented coronaryartery disease (stable or unstable angina, acute coronary syndrome, a history ofmyocardial infarction, or any coronary revascularization), documentedcerebrovascular disease (stroke or transient ischemic attack), known peripheralarterial disease or a history of peripheral arterial revascularization, atrialfibrillation, or valvular heart disease requiring interventions (transcatheteraortic valve replacement or transcatheter mitral-valve repair). Concomitant use of aproton pump inhibitor is strongly recommended in patients receiving aspirinmonotherapy, DAPT (dual antiplatelet therapy; aspirin plus any P2Y12 inhibitors),DAT (dual antithrombotic therapy; antiplatelet drug plus OAC), TAT (tripleantithrombotic therapy; DAPT plus OAC), or OAC monotherapy (warfarin or direct oralanticoagulants) who are at high risk of GI bleeding in order to reduce the risk ofgastric bleed or GI events. Based on clinical guidelines, the use of P2Y12 inhibitormonotherapy (i.e. clopidogrel, ticagrelor, or prasugrel) is not considered in trialenrollment.

2. On the basis of clinical guidelines and expert consensus documents, we defined astudy population with an increased risk of gastrointestinal bleeding if they had aleast 1 or more criteria of the following characteristics. Eligible patients forrandomization must meet at least 1 characteristic of these criteria:

*Definition of patients who are at high risk of gastrointestinal bleeding

1. Age ≥65 years

2. Concomitant use of OAC and any antiplatelet therapy (mono or DAPT) (i.e., DATor TAT)

3. Long-term use of oral NSAIDs (non-steroidal anti-inflammatory drugs) orsteroids or high-dose NSAID therapy even during a relatively short-term period.

4. History of prior GI bleeding events at any time

5. History of a previously complicated ulcer

6. History of peptic ulcer disease or a previously uncomplicated ulcer

7. Documented Helicobacter pylori infection

8. Patients who voluntarily participated in the written agreement

Exclusion Criteria:

1. Active bleeding at the time of inclusion or a history of hereditary or acquiredhemostatic disorder

2. Any clinical contraindication to using of antithrombotic therapies (antiplateletagents or OAC)

3. Concurrent use of PPI or P-CAB within 4 weeks before randomization

4. Hemodynamically unstable conditions at the time of inclusion: cardiogenic shock atthe time of randomization, refractory ventricular arrhythmias, or congestive heartfailure (New York Heart Association class IV).

5. Baseline severe anemia (Hgb <8 g/dl at baseline) or transfusion within 4 weeksbefore randomization

6. Baseline severe thrombocytopenia (platelet count <50,000/mm3)

7. Renal failure dependent on dialysis or severe renal insufficiency (creatinineclearance <15 ml/min)

8. Severe chronic liver disease (defined as variceal haemorrhage, ascites, hepaticencephalopathy, or jaundice)

9. Hypersensitivity or contraindication to PPI, P-CAB, any of the product components,or substituted benzimidazoles

10. Use of clarithromycin and hypersensitivity to macrolide antibiotics for Helicobacterpylori eradication

11. Concomitant use of clarithromycin with terfenadine, cisapride, astemizole, orpimozide for Helicobacter pylori eradication

12. Systemic treatment with strong CYP 3A4 and p-glycoprotein (P-GP) inhibitors (e.g.,systemic azole antimycotics, such as ketoconazole, and human immunodeficiency virus [HIV]-protease inhibitors, such as ritonavir)

13. Patients who take atazanavir, nelfinavir, or rilpivirine-containing products (seeDrug-Drug interaction section)

14. Clinically significant laboratory abnormality at screening (estimated glomerularfiltration rate (eGFR) <15 mL/min or elevated liver enzyme [AST, ALT, ALP, totalbilirubin] > 3 times upper normal limit [UNL] or any other condition that, in theopinion of the Investigator, precludes participation in the study

15. Any known or suspected malignancy

16. Patients with non-cardiac co-morbidities with a life expectancy of less than 12months

17. Patients with active treatment for H-pylori infection

18. Women who are pregnant or breastfeeding or female subjects, premenopausal who arenot surgically sterile, or, if sexually active not practicing an effective method ofbirth control (e.g., prescription oral contraceptives, contraceptive injections,intrauterine device, double-barrier method, contraceptive patch, male partnersterilization) before entry and throughout the study; and, for those of childbearingpotential, who have a positive pregnancy test at screening

19. Participation in another clinical study within 12 months. However, where at leastone or more conditions are satisfied, it could be an exception according to aninvestigator's discretion;

20. Participated in the observational study expected no effect on the safety and/oreffectiveness evaluation of this trial

21. Screening failed before any interventional factor is involved

22. Participated in academic trials like strategic or medical device comparisonstudies conducted under standard therapy provided that there is no additionalrisk or a specific procedure to a subject and no interference between thistrial and other studies