Meta-analysis: Combination Endoscopic and Drug Therapy to Prevent Variceal Rebleeding in Cirrhosis

Meta-analysis: Combination Endoscopic and Drug Therapy to Prevent Variceal Rebleeding in Cirrhosis

From Hospital Universitario Ramón y Cajal, Hospital General Universitario Gregorio Marañón, Alce Ingeniería, Unidad I+D Asociada al Centro Nacional de Biotecnología (CSIC), Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (Ciberehd), Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública (Ciberesp), Universidad Complutense, Universidad de Alcalá, Madrid, Spain.

Abstract

Background: Combining endoscopic therapy and β-blockers may improve outcomes in patients with cirrhosis and bleeding esophageal varices.

Purpose: To assess whether a combination of endoscopic and drug therapy prevents overall and variceal rebleeding and improves survival better than either therapy alone.

Data Sources: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and conference proceedings through 30 December 2007.

Study Selection: Randomized trials comparing endoscopic plus β-blocker therapy with either therapy alone, without language restrictions.

Data Extraction: Two reviewers independently extracted data on interventions and the primary study outcomes of overall rebleeding and mortality. Metaregression and stratified analysis were used to explore heterogeneity.

Data Synthesis: 23 trials (1860 patients) met inclusion criteria. Combination therapy reduced overall rebleeding more than endoscopic therapy alone (pooled relative risk, 0.68 [95% CI, 0.52 to 0.89]; I² = 61%) or β-blocker therapy alone (pooled relative risk, 0.71 [CI, 0.59 to 0.86]; I² = 0%). Combination therapy also reduced variceal rebleeding and variceal recurrence. Reduction in mortality from combination therapy did not statistically significantly differ from that from endoscopic (Peto odds ratio, 0.78 [CI, 0.58 to 1.07) or drug therapy (Peto odds ratio, 0.70 [CI, 0.46 to 1.06]). Effects were independent of the endoscopic procedure (injection sclerotherapy or banding). No trial-level variable associated with the effect was identified through metaregression or stratified analysis.

Limitation: Statistically significant heterogeneity in trial quality and evidence for selective reporting and publication bias were found.

Conclusion: A combination of endoscopic and drug therapy reduces overall and variceal rebleeding in cirrhosis more than either therapy alone.

Article and Author Information

Acknowledgment: The authors thank Ana Burton and Kimiyo Nishimura for their assistance with English and Japanese translations, respectively.
Grant Support: From the Spanish Ministry of Health, Instituto de Salud Carlos III, CM04/00132 (Dr. González) and PI051871, Ciberehd (Drs. Bañares and Albillos); Fundación para la Investigación Biomédica, Hospital General Universitario Gregorio Marañón (Dr. Gomez-Camarero); the Fundación Mutua Madrileña (Drs. Bañares and Albillos [FundacionMM-2006-001 for Dr. Albillos]); and the Spanish Ministry of Education, BFU 2006-09280/BFI (Dr. Albillos). Ciberesp and Ciberehd are funded by the Instituto de Salud Carlos III.
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: Agustín Albillos, MD, PhD, Servicio de Gastroenterología, Hospital Universitario Ramón y Cajal, Carretera de Colmenar km 9.100, 28034 Madrid, Spain; e-mail, aalbillosm{at}meditex.es.
Current Author Addresses: Drs. González and Albillos: Servicio de Gastroenterología, Hospital Universitario Ramón y Cajal, Carretera De Colmenar km 9.100, 28034 Madrid, Spain.
Dr. Zamora: Servicio de Bioestadística, Hospital Universitario Ramón y Cajal, Carretera de Colmenar km 9.100, 28034 Madrid, Spain.
Drs. Gomez-Camarero and Bañares: Servicio de Gastroenterología, Hospital General Universitario Gregorio Marañón, Calle Doctor Esquerdo 46, 28007 Madrid, Spain.
Dr. Molinero: Alce Ingeniería, Calle Fray Luis de León, Bajo D, 28230 Madrid, Spain.