Vasoactive Agents for the Management of Acute Variceal Bleeding: A Systematic Review and Meta-analysis

Abstract

Background and Aims: Vasoactive agents with endoscopic therapy are used to treat acute variceal bleeding (AVB). There are two main groups of vasoactive agents: terlipressin and vasopressin (T-V), and octreotide and somatostatin (O-S). However, the benefit/harm balance is unclear. Our aim was to assess the efficacy and safety of T-V versus O-S for the management of AVB.
 Methods: We performed a systematic search for randomized controlled trials (RCTs) in PubMed, Scopus, and CENTRAL. Our main outcomes were mortality and adverse events. Secondary outcomes were bleeding control, rebleeding, blood transfusion, hospital stay. We evaluated the certainty of evidence using GRADE methodology.
 Results: We included 21 RCTs. The risk of mortality (RR: 1.01; 95%CI: 0.83-1.22), bleeding control (RR: 0.96; 95%CI: 0.91-1.02; I 2 =53%), early rebleeding (RR: 0.91; 95%CI: 0.66-1.24: I 2 =0%), late rebleeding (RR: 0.94; 95 CI: 0.56-1.60; I 2 =0%), blood transfusion (MD: 0.04; 95%CI: -0.31-0.39; I 2 =68%) and hospital stay (MD: -1.06; 95%CI: -2.80-0.69; I 2 =0%) were similar between T-V and O-S groups. Only 15 studies reported adverse events, which were significantly higher in the T-V compared to the O-S group (RR 2.39; 95%CI: 1.58-3.63; I 2 =57%). The certainty of evidence was moderate for the main outcomes, and low or very low for others.
 Conclusions: In cirrhotic patients with AVB, those treated with T-V had similar mortality risk compared to O-S. However, the use of T-V showed an increased risk of adverse events compared to O-S.

Endoscopic diagnosis and management of esophagogastric variceal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline

“…Several systematic reviews/meta-analyses, including numerous RCTs with thousands of patients, have evaluated the efficacy and safety of vasoactive agents in acute EGVH 52 53 54 55 56 57 . In summary, vasoactive agents are superior to no vasoactive treatment in terms of rates of in-hospital mortality, overall mortality, variceal bleeding control, variceal rebleeding, and blood transfusion requirement.…”

Real-time comparison of terlipressin vs. octreotide as an adjuvant treatment in the management of variceal bleeding

“…Although our study did not specify differences in our drug groups playing a role in predicting mortality, a recent meta-analysis consisting of 21 RCTs with a total of 2,431 patients identi ed the risk to be similar between the two drug groups. (13) Overall, our study did not nd much difference in the use of terlipressin and octreotide in terms of mortality. There is some statistically signi cant difference in terms of prolonged hospital stay but, in our opinion, this has no clinical signi cance.…”

Editorial: Shorter course of intravenous terlipressin in acute variceal bleeding ‐ the promise, controversies and future directions

“…6 Growing evidence consistently shows a higher rate of adverse events using terlipressin as compared to somatostatin analogues. 7 Higher adverse events in 3-day terlipressin group could be reduced with continuous infusion of terlipressin. 8 Due to safety concern, the recent AGA practice update recommended octreotide over terlipressin as the first-line vasoactive agent in AVB.…”

“…It is important to note that endoscopic variceal treatment has improved from the very early AVB trials, so the contribution of vasoactive therapy to successful haemostasis has probably decreased 6 . Growing evidence consistently shows a higher rate of adverse events using terlipressin as compared to somatostatin analogues 7 . Higher adverse events in 3‐day terlipressin group could be reduced with continuous infusion of terlipressin 8 .…”