Continuation Versus Discontinuation of Nonselective Beta-Blockers After Transjugular Intrahepatic Portosystemic Shunt Placement: A Real-World, Target-Trial Emulation Analysis.

Background/Objectives: Nonselective beta-blockers (NSBBs) are foundational for variceal bleeding prophylaxis in cirrhosis. After transjugular intrahepatic portosystemic shunt (TIPS) placement, portal pressure is mechanically decompressed, and practice guidance generally supports discontinuing NSBBs when shunt function is adequate and no other indication exists; however, real-world adoption and outcomes associated with post-TIPS NSBB strategies remain incompletely characterized in large, multicenter populations. Methods: We performed a real-world, target-trial emulation in the TriNetX U.S. Collaborative Network using a prespecified 90-day landmark. Adults (≥18 years) with cirrhosis undergoing first TIPS who had NSBB prescribed in the prior year and who survived to post-TIPS day 90 were included. Strategy was classified during days 0-90 (continuation: ≥1 NSBB prescription; discontinuation: none). Propensity score matching (1:1) balanced demographics, comorbidities, portal hypertension complications, and laboratory values (including the components of the Freiburg Index of Post-TIPS Survival [FIPS], Model for End-stage Liver Disease-Sodium [MELD-Na], and Child-Pugh scores). Follow-up began at day 90 and continued through day 365. Primary outcomes were overall survival and transplant-free survival; secondary outcomes were hepatic encephalopathy (HE), esophageal variceal bleeding (EVB), and ICU admission. Results: Among 5111 patients (continuation: n = 2558; discontinuation: n = 2553), 2180 matched pairs were analyzed. One-year survival was similar (89.3% vs. 89.6%; HR: 1.03; 95% CI: 0.84-1.27), as was transplant-free survival (78.8% vs. 77.9%; HR: 0.95; 95% CI: 0.82-1.10). The cause-specific hazard of HE was higher with continuation (HR; 1.29; 95% CI: 1.14-1.46), while those of EVB (HR: 1.08; 95% CI: 0.90-1.29) and ICU admission (HR: 1.02; 95% CI: 0.86-1.22) were similar. Results were consistent in both strict discontinuation and adherence-based sensitivity analyses. Conclusions: In stabilized post-TIPS patients with prior NSBB use, continuation was not associated with improved 1-year survival or transplant-free survival and was associated with a higher cause-specific hazard of HE.