Apixaban-PK Trial: Preventing Portal Hypertension Complications in Cirrhosis

Inclusion Criteria: 1. Adults aged ≥18 years with diagnosed cirrhosis (any etiology), confirmed by histology, transient elastography (≥12.5 kPa), or consistent clinical/imaging findings. 2. Evidence of portal hypertension, defined by: Clinical: presence of varices on endoscopy, ascites, or splenomegaly with thrombocytopenia. 3. Compensated or early decompensated cirrhosis (Child-Pugh B 7-10), with stable liver function defined as no change in Child-Pugh score \>1 point in the preceding 3 months. 4. Screening esophagogastroduodenoscopy (EGD) performed within 6 months prior to enrollment. Patients with high-risk varices (large varices, red wale signs, or history of variceal bleeding) must undergo endoscopic variceal band ligation to obliteration before randomization. 5. Able to provide informed consent and comply with study procedures. Exclusion Criteria: 1. Active gastrointestinal bleeding within 6 weeks prior to enrollment. 2. High bleeding risk: * Platelet count \<50,000/µL at baseline * INR \>1.8 (or \>2.0 if secondary to cirrhosis without additional coagulopathy) * Active peptic ulcer disease * History of intracranial hemorrhage or hemorrhagic stroke * Known bleeding diathesis 3. Severe renal impairment (eGFR \< 30 mL/min/1.73 m²) or on dialysis. 4. Child-Pugh class C or Child-Pugh score ≥10. 5. History of hypersensitivity to apixaban or carvedilol. 6. Pregnancy, breastfeeding, or unwillingness to use effective contraception during the study period. 7. Concurrent anticoagulant or antiplatelet therapy (including aspirin, clopidogrel, warfarin, or other DOACs) that cannot be safely discontinued. A washout period of at least 5 half-lives is required before randomization. 8. Use of NSAIDs, SSRIs, or other medications that significantly increase bleeding risk, unless approved by the PI with clear risk-benefit justification. 9. Active hepatocellular carcinoma (HCC) outside Milan criteria or with vascular invasion. 10. Current or planned liver transplantation.