Carvedilol vs endoscopic variceal ligation for primary and secondary prevention of variceal bleeding: Systematic review and metaanalysis
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摘要
BACKGROUND Variceal hemorrhage is associated with high mortality and is the cause of death for 20–30% of patients with cirrhosis. Nonselective β blockers(NSBBs) or endoscopic variceal ligation(EVL) are recommended for primary prevention of variceal bleeding in patients with medium to large esophageal varices.Meanwhile, combination of EVL and NSBBs is the recommended approach for the secondary prevention. Carvedilol has greater efficacy than other NSBBs as it decreases intrahepatic resistance. We hypothesized that there was no difference between carvedilol and EVL intervention for primary and secondary prevention of variceal bleeding in cirrhosis patients.AIM To evaluate the efficacy of carvedilol compared to EVL for primary and secondary prevention of variceal bleeding in cirrhotic patients METHODS We searched relevant literatures in major journal databases(CENTRAL,MEDLINE, and EMBASE) from March to August 2018. Patients with cirrhosis and portal hypertension, regardless of aetiology and severity, with or without a history of variceal bleeding, and aged ≥ 18 years old were included in this review.Only randomized controlled trials(RCTs) that compared the efficacy of carvedilol and that of EVL for primary and secondary prevention of variceal bleeding and mortality in patients with cirrhosis and portal hypertension were considered, irrespective of publication status, year of publication, and language.RESULTS Seven RCTs were included. In four trials assessing the primary prevention, no significant difference was found on the events of variceal bleeding(RR: 0.74,95%CI: 0.37-1.49), all-cause mortality(RR: 1.10, 95%CI: 0.76-1.58), and bleedingrelated mortality(RR: 1.02, 95%CI: 0.34-3.10) in patients who were treated with carvedilol compared to EVL. In three trials assessing secondary prevention, there was no difference between two interventions for the incidence of rebleeding(RR:1.10, 95%CI: 0.75-1.61). The fixed-effect model showed that, compared to EVL,carvedilol decreased all-cause mortality by 49%(RR: 0.51, 95%CI: 0.33-0.79), with little or no evidence of heterogeneity.CONCLUSION Carvedilol had similar efficacy to EVL in preventing the first variceal bleeding in cirrhosis patients with esophageal varices. It was superior to EVL alone for secondary prevention of variceal bleeding in regard to all-cause mortality reduction.
BACKGROUND Variceal hemorrhage is associated with high mortality and is the cause of death for 20–30% of patients with cirrhosis. Nonselective β blockers(NSBBs) or endoscopic variceal ligation(EVL) are recommended for primary prevention of variceal bleeding in patients with medium to large esophageal varices.Meanwhile, combination of EVL and NSBBs is the recommended approach for the secondary prevention. Carvedilol has greater efficacy than other NSBBs as it decreases intrahepatic resistance. We hypothesized that there was no difference between carvedilol and EVL intervention for primary and secondary prevention of variceal bleeding in cirrhosis patients.AIM To evaluate the efficacy of carvedilol compared to EVL for primary and secondary prevention of variceal bleeding in cirrhotic patients METHODS We searched relevant literatures in major journal databases(CENTRAL,MEDLINE, and EMBASE) from March to August 2018. Patients with cirrhosis and portal hypertension, regardless of aetiology and severity, with or without a history of variceal bleeding, and aged ≥ 18 years old were included in this review.Only randomized controlled trials(RCTs) that compared the efficacy of carvedilol and that of EVL for primary and secondary prevention of variceal bleeding and mortality in patients with cirrhosis and portal hypertension were considered, irrespective of publication status, year of publication, and language.RESULTS Seven RCTs were included. In four trials assessing the primary prevention, no significant difference was found on the events of variceal bleeding(RR: 0.74,95%CI: 0.37-1.49), all-cause mortality(RR: 1.10, 95%CI: 0.76-1.58), and bleedingrelated mortality(RR: 1.02, 95%CI: 0.34-3.10) in patients who were treated with carvedilol compared to EVL. In three trials assessing secondary prevention, there was no difference between two interventions for the incidence of rebleeding(RR:1.10, 95%CI: 0.75-1.61). The fixed-effect model showed that, compared to EVL,carvedilol decreased all-cause mortality by 49%(RR: 0.51, 95%CI: 0.33-0.79), with little or no evidence of heterogeneity.CONCLUSION Carvedilol had similar efficacy to EVL in preventing the first variceal bleeding in cirrhosis patients with esophageal varices. It was superior to EVL alone for secondary prevention of variceal bleeding in regard to all-cause mortality reduction.
BACKGROUND Variceal hemorrhage is associated with high mortality and is the cause of death for 20–30% of patients with cirrhosis. Nonselective β blockers(NSBBs) or endoscopic variceal ligation(EVL) are recommended for primary prevention of variceal bleeding in patients with medium to large esophageal varices.Meanwhile, combination of EVL and NSBBs is the recommended approach for the secondary prevention. Carvedilol has greater efficacy than other NSBBs as it decreases intrahepatic resistance. We hypothesized that there was no difference between carvedilol and EVL intervention for primary and secondary prevention of variceal bleeding in cirrhosis patients.AIM To evaluate the efficacy of carvedilol compared to EVL for primary and secondary prevention of variceal bleeding in cirrhotic patients METHODS We searched relevant literatures in major journal databases(CENTRAL,MEDLINE, and EMBASE) from March to August 2018. Patients with cirrhosis and portal hypertension, regardless of aetiology and severity, with or without a history of variceal bleeding, and aged ≥ 18 years old were included in this review.Only randomized controlled trials(RCTs) that compared the efficacy of carvedilol and that of EVL for primary and secondary prevention of variceal bleeding and mortality in patients with cirrhosis and portal hypertension were considered, irrespective of publication status, year of publication, and language.RESULTS Seven RCTs were included. In four trials assessing the primary prevention, no significant difference was found on the events of variceal bleeding(RR: 0.74,95%CI: 0.37-1.49), all-cause mortality(RR: 1.10, 95%CI: 0.76-1.58), and bleedingrelated mortality(RR: 1.02, 95%CI: 0.34-3.10) in patients who were treated with carvedilol compared to EVL. In three trials assessing secondary prevention, there was no difference between two interventions for the incidence of rebleeding(RR:1.10, 95%CI: 0.75-1.61). The fixed-effect model showed that, compared to EVL,carvedilol decreased all-cause mortality by 49%(RR: 0.51, 95%CI: 0.33-0.79), with little or no evidence of heterogeneity.CONCLUSION Carvedilol had similar efficacy to EVL in preventing the first variceal bleeding in cirrhosis patients with esophageal varices. It was superior to EVL alone for secondary prevention of variceal bleeding in regard to all-cause mortality reduction.
引文
1 Kasper D,Fauci A,Hauser S,Longo D,Jameson J,Loscalzo J.Harrison's principles of internal medicine.19th ed.New York:Mc Graw Hill 2015;2062-2064
2 Garcia-Tsao G,Abraldes JG,Berzigotti A,Bosch J.Portal hypertensive bleeding in cirrhosis:Risk stratification,diagnosis,and management:2016 practice guidance by the American Association for the study of liver diseases.Hepatology 2017;65:310-335[PMID:27786365 DOI:10.1002/hep.28906]
3 de Franchis R;Baveno V Faculty.Revising consensus in portal hypertension:report of the Baveno Vconsensus workshop on methodology of diagnosis and therapy in portal hypertension.J Hepatol 2010;53:762-768[PMID:20638742 DOI:10.1016/j.jhep.2010.06.004]
4 Turnes J,Garcia-Pagan JC,Abraldes JG,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 JGastroenterol 2006;101:506-512[PMID:16542287 DOI:10.1111/j.1572-0241.2006.00453.x]
5 Villanueva C,Aracil C,Colomo A,Hernández-Gea V,López-Balaguer JM,Alvarez-Urturi C,Torras X,BalanzóJ,Guarner C.Acute hemodynamic response to beta-blockers and prediction of long-term outcome in primary prophylaxis of variceal bleeding.Gastroenterology 2009;137:119-128[PMID:19344721DOI:10.1053/j.gastro.2009.03.048]
6 Sinagra E,Perricone G,D'Amico M,TinèF,D'Amico G.Systematic review with meta-analysis:the haemodynamic effects of carvedilol compared with propranolol for portal hypertension in cirrhosis.Aliment Pharmacol Ther 2014;39:557-568[PMID:24461301 DOI:10.1111/apt.12634]
7 Gluud LL,Krag A.Banding ligation versus beta-blockers for primary prevention in oesophageal varices in adults.Cochrane Database Syst Rev 2012;CD004544[PMID:22895942 DOI:10.1002/14651858.CD004544.pub2]
8 Li T,Ke W,Sun P,Chen X,Belgaumkar A,Huang Y,Xian W,Li J,Zheng Q.Carvedilol for portal hypertension in cirrhosis:systematic review with meta-analysis.BMJ Open 2016;6:e010902[PMID:27147389 DOI:10.1136/bmjopen-2015-010902]
9 Tripathi D,Ferguson JW,Kochar N,Leithead JA,Therapondos G,McAvoy NC,Stanley AJ,Forrest EH,Hislop WS,Mills PR,Hayes PC.Randomized controlled trial of carvedilol versus variceal band ligation for the prevention of the first variceal bleed.Hepatology 2009;50:825-833[PMID:19610055 DOI:10.1002/hep.23045]
10 Shah HA,Azam Z,Rauf J,Abid S,Hamid S,Jafri W,Khalid A,Ismail FW,Parkash O,Subhan A,Munir SM.Carvedilol vs.esophageal variceal band ligation in the primary prophylaxis of variceal hemorrhage:a multicentre randomized controlled trial.J Hepatol 2014;60:757-764[PMID:24291366 DOI:10.1016/j.jhep.2013.11.019]
11 Abd ElRahim AY,Fouad R,Khairy M,Elsharkawy A,Fathalah W,Khatamish H,Khorshid O,Moussa M,Seyam M.Efficacy of carvedilol versus propranolol versus variceal band ligation for primary prevention of variceal bleeding.Hepatol Int 2018;12:75-82[PMID:29185106 DOI:10.1007/s12072-017-9835-9]
12 Khan MS,Majeed A,Ghauri F,Asghar U,Waheed I.Comparison of carvedilol and esophageal variceal band ligation for prevention of variceal bleed among cirrhotic patient.Pak J Health Med Sci 2017;11:1046-1048
13 Kumar P,Kumar R,Saxena KN,Misra SP,Dwivedi,M.Secondary prophylaxis of variceal hemorrhage:a comparative study of band ligation,carvedilol,and propranolol plus isosorbide mononitrate.Indian JGastroenterol 2015;34:1-104[DOI:10.1007/s12664-015-0600-5]
14 Stanley AJ,Dickson S,Hayes PC,Forrest EH,Mills PR,Tripathi D,Leithead JA,MacBeth K,Smith L,Gaya DR,Suzuki H,Young D.Multicentre randomised controlled study comparing carvedilol with variceal band ligation in the prevention of variceal rebleeding.J Hepatol 2014;61:1014-1019[PMID:24953021 DOI:10.1016/j.jhep.2014.06.015]
15 Smith LA,Dickson S,Hayes PC,Tripathi D,Ferguson W,Forrest EH,Gaya DR,Mills PR,Suzuki H,Young D,Stanley AJ.Multicentre randomised controlled study comparing carvedilol with endoscopic band ligation in the prevention of variceal rebleeding.Gut 2013;62:A1-A2[DOI:10.1136/gutjnl-2013-304907.003]
16 Karadsheh Z,Allison H.Primary prevention of variceal bleeding:pharmacological therapy versus endoscopic banding.N Am J Med Sci 2013;5:573-579[PMID:24350068 DOI:10.4103/1947-2714.120791]
17 Brunner F,Berzigotti A,Bosch J.Prevention and treatment of variceal haemorrhage in 2017.Liver Int2017;37 Suppl 1:104-115[PMID:28052623 DOI:10.1111/liv.13277]
2 Garcia-Tsao G,Abraldes JG,Berzigotti A,Bosch J.Portal hypertensive bleeding in cirrhosis:Risk stratification,diagnosis,and management:2016 practice guidance by the American Association for the study of liver diseases.Hepatology 2017;65:310-335[PMID:27786365 DOI:10.1002/hep.28906]
3 de Franchis R;Baveno V Faculty.Revising consensus in portal hypertension:report of the Baveno Vconsensus workshop on methodology of diagnosis and therapy in portal hypertension.J Hepatol 2010;53:762-768[PMID:20638742 DOI:10.1016/j.jhep.2010.06.004]
4 Turnes J,Garcia-Pagan JC,Abraldes JG,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 JGastroenterol 2006;101:506-512[PMID:16542287 DOI:10.1111/j.1572-0241.2006.00453.x]
5 Villanueva C,Aracil C,Colomo A,Hernández-Gea V,López-Balaguer JM,Alvarez-Urturi C,Torras X,BalanzóJ,Guarner C.Acute hemodynamic response to beta-blockers and prediction of long-term outcome in primary prophylaxis of variceal bleeding.Gastroenterology 2009;137:119-128[PMID:19344721DOI:10.1053/j.gastro.2009.03.048]
6 Sinagra E,Perricone G,D'Amico M,TinèF,D'Amico G.Systematic review with meta-analysis:the haemodynamic effects of carvedilol compared with propranolol for portal hypertension in cirrhosis.Aliment Pharmacol Ther 2014;39:557-568[PMID:24461301 DOI:10.1111/apt.12634]
7 Gluud LL,Krag A.Banding ligation versus beta-blockers for primary prevention in oesophageal varices in adults.Cochrane Database Syst Rev 2012;CD004544[PMID:22895942 DOI:10.1002/14651858.CD004544.pub2]
8 Li T,Ke W,Sun P,Chen X,Belgaumkar A,Huang Y,Xian W,Li J,Zheng Q.Carvedilol for portal hypertension in cirrhosis:systematic review with meta-analysis.BMJ Open 2016;6:e010902[PMID:27147389 DOI:10.1136/bmjopen-2015-010902]
9 Tripathi D,Ferguson JW,Kochar N,Leithead JA,Therapondos G,McAvoy NC,Stanley AJ,Forrest EH,Hislop WS,Mills PR,Hayes PC.Randomized controlled trial of carvedilol versus variceal band ligation for the prevention of the first variceal bleed.Hepatology 2009;50:825-833[PMID:19610055 DOI:10.1002/hep.23045]
10 Shah HA,Azam Z,Rauf J,Abid S,Hamid S,Jafri W,Khalid A,Ismail FW,Parkash O,Subhan A,Munir SM.Carvedilol vs.esophageal variceal band ligation in the primary prophylaxis of variceal hemorrhage:a multicentre randomized controlled trial.J Hepatol 2014;60:757-764[PMID:24291366 DOI:10.1016/j.jhep.2013.11.019]
11 Abd ElRahim AY,Fouad R,Khairy M,Elsharkawy A,Fathalah W,Khatamish H,Khorshid O,Moussa M,Seyam M.Efficacy of carvedilol versus propranolol versus variceal band ligation for primary prevention of variceal bleeding.Hepatol Int 2018;12:75-82[PMID:29185106 DOI:10.1007/s12072-017-9835-9]
12 Khan MS,Majeed A,Ghauri F,Asghar U,Waheed I.Comparison of carvedilol and esophageal variceal band ligation for prevention of variceal bleed among cirrhotic patient.Pak J Health Med Sci 2017;11:1046-1048
13 Kumar P,Kumar R,Saxena KN,Misra SP,Dwivedi,M.Secondary prophylaxis of variceal hemorrhage:a comparative study of band ligation,carvedilol,and propranolol plus isosorbide mononitrate.Indian JGastroenterol 2015;34:1-104[DOI:10.1007/s12664-015-0600-5]
14 Stanley AJ,Dickson S,Hayes PC,Forrest EH,Mills PR,Tripathi D,Leithead JA,MacBeth K,Smith L,Gaya DR,Suzuki H,Young D.Multicentre randomised controlled study comparing carvedilol with variceal band ligation in the prevention of variceal rebleeding.J Hepatol 2014;61:1014-1019[PMID:24953021 DOI:10.1016/j.jhep.2014.06.015]
15 Smith LA,Dickson S,Hayes PC,Tripathi D,Ferguson W,Forrest EH,Gaya DR,Mills PR,Suzuki H,Young D,Stanley AJ.Multicentre randomised controlled study comparing carvedilol with endoscopic band ligation in the prevention of variceal rebleeding.Gut 2013;62:A1-A2[DOI:10.1136/gutjnl-2013-304907.003]
16 Karadsheh Z,Allison H.Primary prevention of variceal bleeding:pharmacological therapy versus endoscopic banding.N Am J Med Sci 2013;5:573-579[PMID:24350068 DOI:10.4103/1947-2714.120791]
17 Brunner F,Berzigotti A,Bosch J.Prevention and treatment of variceal haemorrhage in 2017.Liver Int2017;37 Suppl 1:104-115[PMID:28052623 DOI:10.1111/liv.13277]