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Carvedilol vs. esophageal variceal band ligation in the primary prophylaxis of variceal hemorrhage: A multicentre randomized controlled trial

Published:December 02, 2013DOI:https://doi.org/10.1016/j.jhep.2013.11.019

      Background & Aims

      Esophageal variceal bleed is a major problem in patients with cirrhosis. Endoscopic variceal ligation (EVL) has been shown to be equal to or better than propranolol in preventing first bleed. Carvedilol is a non-selective β blocker with alpha-1 adrenergic blocker activity. Hemodynamic studies have shown carvedilol to be more effective than propranolol at reducing portal pressure. We compared efficacy of carvedilol with EVL for primary prophylaxis of esophageal variceal bleed.

      Methods

      Cirrhotic patients with esophageal varices were randomized to carvedilol 12.5 mg daily or EVL at three university hospitals of Pakistan. End points were esophageal variceal bleeding, death or liver transplant.

      Results

      Two hundred and nine patients were evaluated. Eighty two and eighty six patients were randomized in carvedilol and EVL arms respectively. Mean age was 48 ± 12.2 years; 122 (72.7%) were males; 89.9% had viral cirrhosis; mean Child-Pugh score was 7.3 ± 1.6 and mean follow up was 13.3 ± 12.1 months (range 1–50 months). Both EVL and carvedilol groups had comparable variceal bleeding rates (8.5% vs. 6.9%), bleed related mortality (4.6% vs. 4.9%) and overall mortality (12.8% vs. 19.5%) respectively. Adverse events in carvedilol group were hypotension (n = 2), requiring cessation of therapy, while transient nausea (n = 18) and dyspnea (n = 30) resolved spontaneously. In the EVL arm, post banding ulcer bleed (n = 1) and chest pain (n = 17), were termed as serious adverse events while transient dysphagia (n = 58) resolved without treatment.

      Conclusions

      Although our study is underpowered, the findings suggest that carvedilol is probably not superior to EVL in preventing first variceal bleed in patients with viral cirrhosis.

      Abbreviations:

      EVL (esophageal variceal ligation), EVB (esophageal variceal bleed), HCV (hepatitis C virus), HBV (hepatitis B virus), HDV (hepatitis delta virus), PVT (portal vein thrombosis), HCC (hepatocellular carcinoma), GCP (good clinical practice), ER (emergency room), GV (gastric varix), EV (esophageal varix), EKG (electrocardiogram), BCU (bleeding care unit), Hb (hemoglobin), ITT (intention to treat), CI (confidence interval), IHD (ischemic heart disease), HVPG (hepatic venous pressure gradient), EGD (esophago-gastro-duodenoscopy), TIPS (transjugular intrahepatic portosystemic shunt), PSE (porto-systemic encephalopathy)

      Keywords

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      References

        • Merli M.
        • Nicolini G.
        • Angeloni S.
        • Rinaldi V.
        • De Santis A.
        • Merkel C.
        • et al.
        Incidence and natural history of small esophageal varices in cirrhotic patients.
        J Hepatol. 2003; 38: 266-272
        • Groszmann R.J.
        • Bosch J.
        • Grace N.D.
        • Conn H.O.
        • Garcia-Tsao G.
        • Navasa M.
        • et al.
        Hemodynamic events in a prospective randomized trial of propranolol vs. placebo in the prevention of a first variceal hemorrhage.
        Gastroenterology. 1990; 99: 1401-1407
        • Turnes J.
        • Garcia-Pagan J.C.
        • Abraldes J.G.
        • Hernandez-Guerra M.
        • Dell’Era A.
        • Bosch J.
        Pharmacological reduction of portal pressure and long-term risk of first variceal bleeding in patients with cirrhosis.
        Am J Gastroenterol. 2006; 101: 506-512
        • Villanueva C.
        • Aracil C.
        • Colomo A.
        • Hernandez-Gea V.
        • Lopez-Balaguer J.M.
        • Alvarez-Urturi C.
        • et al.
        Acute hemodynamic response to beta-blockers and prediction of long-term outcome in primary prophylaxis of variceal bleeding.
        Gastroenterology. 2009; 137: 119-128
        • Tripathi D.
        • Graham C.
        • Hayes P.C.
        Variceal band ligation vs. beta-blockers for primary prevention of variceal bleeding: a meta-analysis.
        Eur J Gastroenterol Hepatol. 2007; 19: 835-845
        • Funakoshi N.
        • Duny Y.
        • Valats J.C.
        • Segalas-Largey F.
        • Flori N.
        • Bismuth M.
        • et al.
        Meta-analysis: beta-blockers vs. banding ligation for primary prophylaxis of esophageal variceal bleeding.
        Ann Hepatol. 2012; 11: 369-383
        • Bosch J.
        Carvedilol for portal hypertension in patients with cirrhosis.
        Hepatology. 2010; 51: 2214-2218
        • Hemstreet B.A.
        Evaluation of carvedilol for the treatment of portal hypertension.
        Pharmacotherapy. 2004; 24: 94-104
        • Tsochatzis E.A.
        • Triantos C.K.
        • Burroughs A.K.
        Gastrointestinal bleeding: carvedilol-the best beta-blocker for primary prophylaxis?.
        Nat Rev Gastroenterol Hepatol. 2009; 6: 692-694
        • Albillos A.
        • Lledo J.L.
        • Banares R.
        • Rossi I.
        • Iborra J.
        • Calleja J.L.
        • et al.
        Hemodynamic effects of alpha-adrenergic blockade with prazosin in cirrhotic patients with portal hypertension.
        Hepatology. 1994; 20: 611-617
        • Banares R.
        • Moitinho E.
        • Piqueras B.
        • Casado M.
        • Garcia-Pagan J.C.
        • De Digego A.
        • et al.
        Carvedilol, a new beta-blocker with intrinsic anti-Alpha-adrenergic activity, has a greater portal hypotensive effect than propranolol in patients with cirrhosis.
        Hepatology. 1999; 30: 79-83
        • Banares R.
        • Moitinho E.
        • Matilla A.
        • Garcia-Pagan J.C.
        • Lampreave J.L.
        • Piera C.
        • et al.
        Randomized comparison of long term carvedilol and propranolol administration in the treatment of portal hypertension I cirrhosis.
        Hepatology. 2002; 36: 1367-1373
        • Tripathi D.
        • Therapondos G.
        • Lui H.F.
        • Stanley A.J.
        • Hayes P.C.
        Haemodynamic effects of acute and chronic administration of low-dose carvedilol, a vasodilating beta-blocker, in patients with cirrhosis and portal hypertension.
        Aliment Pharmacol Ther. 2002; 16: 373-380
        • Stanley A.J.
        • Therapondos G.
        • Helmy A.
        • Hayes P.C.
        Acute and chronic haemodynamic and renal effects of carvedilol in patients with cirrhosis.
        J Hepatol. 1999; 30: 479-484
        • Lin H.C.
        • Yang Y.Y.
        • Hou M.C.
        • Huang Y.T.
        • Lee F.Y.
        • Lee S.D.
        Acute administration of carvedilol is more effective than propranolol plus isosorbide-5-mononitrate in the reduction of portal pressure in patients with viral cirrhosis.
        Am J Gastroenterol. 2004; 99: 1953-1958
        • Forrest E.H.
        • Bouchier I.A.
        • Hayes P.C.
        Acute haemodynamic changes after oral carvedilol, a vasodilating beta-blocker, in patients with cirrhosis.
        J Hepatol. 1996; 25: 909-915
        • Tripathi D.
        • Ferguson J.W.
        • Kochar N.
        • Leithead J.A.
        • Therapondos G.
        • McAvoy N.C.
        • et al.
        Randomized controlled trial of carvedilol vs. variceal band ligation for the prevention of the first variceal bleed.
        Hepatology. 2009; 50: 825-833
        • de Franchis R.
        Revising consensus in portal hypertension: report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension.
        J Hepatol. 2010; 53: 762-768
        • Sarin S.K.
        • Lamba G.S.
        • Kumar M.
        • Misra A.
        • Murthy N.S.
        Comparison of endoscopic ligation and propranolol for the primary prevention of variceal bleeding.
        N Engl J Med. 1999; 340: 988-993
        • Reiberger T.
        • Ulbrich G.
        • Ferlitsch A.
        • Payer B.A.
        • Schwabl P.
        • Pinter M.
        • et al.
        Carvedilol for primary prophylaxis of variceal bleeding in cirrhotic patients with haemodynamic non-response to propranolol.
        Gut. 2013; 62: 1634-1641
      1. Gluud LL, Krag A. Banding ligation versus beta-blockers for primary prevention in oesophageal varices in adults. Cochrane Database Syst Rev 2012;8:CD004544.