title: Prevention of Rebleeding From Esophageal Varices in Patients With Cirrhosis Receiving Small-Diameter Stents Versus Hemodynamically Controlled Medical Therapy.
abstract: OBJECTIVE
  Patients with cirrhosis and variceal hemorrhage have a high risk of rebleeding. We performed a prospective randomized trial to compare the prevention of rebleeding in patients given a small-diameter covered stent vs those given hepatic venous pressure gradient (HVPG)-based medical therapy prophylaxis.
  
  
  METHODS
  We performed an open-label study of patients with cirrhosis (92% Child class A or B, 70% alcoholic) treated at 10 medical centers in Germany. Patients were assigned randomly more than 5 days after variceal hemorrhage to groups given a small covered transjugular intrahepatic portosystemic stent-shunt (TIPS) (8 mm; n = 90), or medical reduction of portal pressure (propranolol and isosorbide-5-mononitrate; n = 95). HVPG was determined at the time patients were assigned to groups (baseline) and 2 weeks later. In the medical group, patients with an adequate reduction in HVPG (responders) remained on the drugs whereas nonresponders underwent only variceal band ligation. The study was closed 10 months after the last patient was assigned to a group. The primary end point was variceal rebleeding. Survival, safety (adverse events), and quality of life (based on the Short Form-36 health survey) were secondary outcome measures.
  
  
  RESULTS
  A significantly smaller proportion of patients in the TIPS group had rebleeding within 2 years (7%) than in the medical group (26%) (P = .002). A slightly higher proportion of patients in the TIPS group experienced adverse events, including encephalopathy (18% vs 8% for medical treatment; P = .05). Rebleeding occurred in 6 of 23 patients (26%) receiving medical treatment before hemodynamic control was possible. Per-protocol analysis showed that rebleeding occurred in a smaller proportion of the 32 responders (18%) than in nonresponders who received variceal band ligation (31%) (P = .06). Fifteen patients from the medical group (16%) underwent TIPS placement during follow-up evaluation, mainly for refractory ascites. Survival time and quality of life did not differ between both randomized groups.
  
  
  CONCLUSIONS
  Placement of a small-diameter, covered TIPS was straightforward and prevented variceal rebleeding in patients with Child A or B cirrhosis more effectively than drugs, which often required step-by-step therapy. However, TIPS did not increase survival time or quality of life and produced slightly more adverse events. Clinical Trial no: ISRCTN 16334693.
authors.affiliation: Department of Internal Medicine I, University of Bonn, Bonn, Germany. Electronic address: sauerbruch@uni-bonn.de.
authors.forename: Tilman
authors.initials: T
authors.lastname: Sauerbruch
authors.affiliation: Department of Internal Medicine I, University of Bonn, Bonn, Germany; Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Mengel
authors.affiliation: Department of Internal Medicine I, University of Ulm, Ulm, Germany; Department of Internal Medicine I, University of Halle, Halle, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Dollinger
authors.affiliation: Department of Internal Medicine I, University of Halle, Halle, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Zipprich
authors.affiliation: Department of Internal Medicine II, University of Freiburg, Freiburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Rössle
authors.affiliation: Department of Internal Medicine II, University of Freiburg, Freiburg, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Panther
authors.affiliation: Department of Internal Medicine I, University of Regensburg, Regensburg, Germany; Department of Visceral Surgery and Medicine, University of Bern, Bern, Switzerland.
authors.forename: Reiner
authors.initials: R
authors.lastname: Wiest
authors.affiliation: Klinikum Ludwigsburg, Ludwigsburg, Germany.
authors.forename: Karel
authors.initials: K
authors.lastname: Caca
authors.affiliation: Department of Gastroenterology, University of Leipzig, Leipzig, Germany.
authors.forename: Albrecht
authors.initials: A
authors.lastname: Hoffmeister
authors.affiliation: Department of Internal Medicine III, University of Aachen, Aachen, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Lutz
authors.affiliation: Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Schoo
authors.affiliation: Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Lorenzen
authors.affiliation: Department of Internal Medicine I, University of Bonn, Bonn, Germany.
authors.forename: Jonel
authors.initials: J
authors.lastname: Trebicka
authors.affiliation: Department of Internal Medicine I, University of Bonn, Bonn, Germany; Department of Internal Medicine II, Saarland University, Homburg, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Appenrodt
authors.affiliation: Department of Internal Medicine I, University of Bonn, Bonn, Germany; Medizinische Klinik, Helios Klinikum Siegburg, Siegburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schepke
authors.affiliation: Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Fimmers
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004932:Esophageal and Gastric Varices / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000503:physiopathology / Q000517:prevention & control*; D005858:Germany; D006801:Humans; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000150:complications* / Q000175:diagnosis / Q000401:mortality; D008297:Male; D008875:Middle Aged; D020030:Nitric Oxide Donors / Q000627:therapeutic use; D019168:Portasystemic Shunt, Transjugular Intrahepatic / Q000009:adverse effects / Q000295:instrumentation* / Q000401:mortality; D011433:Propranolol / Q000627:therapeutic use; D011446:Prospective Studies; D011474:Prosthesis Design; D011788:Quality of Life; D012008:Recurrence; D015607:Stents; D013997:Time Factors; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014690:Venous Pressure / Q000187:drug effects*
chemical_list: D000319:Adrenergic beta-Antagonists; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D011433:Propranolol; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate
keywords: Advanced Liver Disease; HVPG; Nonselective β-Blocker; TIPS