Risk and Predictors of Variceal Bleeding in Cirrhosis Patients Receiving Primary Prophylaxis With Non-Selective Beta-Blockers.
Prior studies have demonstrated the efficacy of non-selective beta-blockers (NSBB) in preventing first variceal bleeding in patients with cirrhosis. However, little is known about the overall effectiveness of NSBB in routine clinical care.



We conducted a retrospective cohort study of cirrhotic patients without prior bleeding who initiated a NSBB (propranolol, nadolol) at any Veterans Administration facility between 2008 and 2013. The primary outcome was variceal bleeding within 12 months. We conducted Cox-proportional hazards analyses to identify demographic, clinical, and NSBB-related (type of NSBB, mean dose, dose change, and heart rate response) factors associated with variceal bleeding.



Of 5,775 patients, 678 (11.7%) developed variceal bleeding. Mean daily dose of NSBB was <40 mg in 58.8%, 18.1% had either upward or downward titration in NSBB dose, and 9.8% had hemodynamic response. Patients who were younger, with ascites, greater medical comorbidity, and higher MELD (Model for end-stage liver disease) scores had a higher risk of variceal bleeding. Patients on a higher daily dose (>60 vs. <40 mg, adjusted hazard ratio (HR) 0.64; 95% confidence interval (CI): 0.51-0.81), who had either upward or downward dose titration (adjusted HR 0.69; 95% CI: 0.52-0.90 and 0.64; 95% CI 0.45-0.90, respectively), and those who achieved hemodynamic response (adjusted HR 0.75; 95% CI=0.57-1.0) had lower risk.



Approximately 12% of patients bled while being on NSBB for primary prophylaxis. A higher NSBB dose and dose titration were protective; yet most patients did not have the NSBB dose titrated to the recommended levels. Our data highlight the need for careful monitoring of cirrhotic patients on NSBB.
Section of Gastroenterology and Hepatology, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA.
Richa
R
Shukla
Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA.|Department of Medicine, Section of Health Services Research, Baylor College of Medicine, Houston, Texas, USA.
Jennifer
J
Kramer
Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA.|Department of Medicine, Section of Health Services Research, Baylor College of Medicine, Houston, Texas, USA.
Yumei
Y
Cao
Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA.|Department of Medicine, Section of Health Services Research, Baylor College of Medicine, Houston, Texas, USA.
Jun
J
Ying
Section of Gastroenterology and Hepatology, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA.
Aylin
A
Tansel
Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA.|Department of Medicine, Section of Health Services Research, Baylor College of Medicine, Houston, Texas, USA.
Annette
A
Walder
Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA.
Shailesh
S
Advani
Section of Gastroenterology and Hepatology, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA.|Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA.|Department of Medicine, Section of Health Services Research, Baylor College of Medicine, Houston, Texas, USA.
Hashem B
HB
El-Serag
Section of Gastroenterology and Hepatology, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA.|Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA.|Department of Medicine, Section of Health Services Research, Baylor College of Medicine, Houston, Texas, USA.
Fasiha
F
Kanwal
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000367:Age Factors; D000368:Aged; D001201:Ascites / Q000453:epidemiology; D015331:Cohort Studies; D015897:Comorbidity; D004305:Dose-Response Relationship, Drug; D004932:Esophageal and Gastric Varices / Q000150:complications* / Q000453:epidemiology; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D006339:Heart Rate; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009248:Nadolol / Q000627:therapeutic use; D011322:Primary Prevention; D016016:Proportional Hazards Models; D011433:Propranolol / Q000627:therapeutic use; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States; D014493:United States Department of Veterans Affairs
D000319:Adrenergic beta-Antagonists; D009248:Nadolol; D011433:Propranolol
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