Terlipressin for acute esophageal variceal hemorrhage - PubMed (original) (raw)

Review

Terlipressin for acute esophageal variceal hemorrhage

G Ioannou et al. Cochrane Database Syst Rev. 2001.

Update in

Abstract

Background: Terlipressin (triglycyl lysine vasopressin) is a synthetic analogue of vasopressin, which has been used in the treatment of acute variceal hemorrhage. In contrast to vasopressin, terlipressin can be administered as intermittent injections instead of continuous intravenous infusion and it has a safer adverse reactions profile. However, its effectiveness remains uncertain.

Objectives: To determine if treatment with terlipressin improves outcome in acute esophageal variceal hemorrhage and is safe.

Search strategy: Randomized clinical trials were identified by searching the following databases: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, the Cochrane Hepato-Biliary Group Controlled Trials Register, Biosis, and Current Contents. The bibliographies of identified publications were checked. Experts in the field and the manufacturers of terlipressin were contacted.

Selection criteria: All randomized clinical trials which compared terlipressin with: (a) placebo or no treatment, (b) balloon tamponade, (c) endoscopic treatment, (d) octreotide, (e) somatostatin and (f) vasopressin, in the setting of acute variceal hemorrhage.

Data collection and analysis: Eligibility, trial quality assessment and data extraction were done independently by two reviewers. The primary outcome measure was mortality. Secondary outcomes were failure of initial hemostasis, rebleeding, procedures required for uncontrolled bleeding or rebleeding, transfusion requirements and length of hospitalization.

Main results: Twenty studies were identified for all the comparison groups, involving 1609 patients. There were seven studies (with 443 patients) comparing terlipressin to placebo, five of which were considered to be high quality studies based on the Jadad scale. The meta-analysis indicates that terlipressin was associated with a statistically significant reduction in all cause mortality compared to placebo (relative risk 0.66, 95% confidence interval 0.49 to 0.88). Three studies (with 302 patients) were identified comparing terlipressin to somatostatin, two of which were high quality studies; only one high quality study (219 patients) comparing terlipressin to endoscopic treatment was identified. Within the limited power provided by these small numbers of patients, no statistically significant difference was demonstrated between terlipressin and either somatostatin or endoscopic treatment in any of the outcomes. For the remaining comparison groups (terlipressin versus balloon tamponade, terlipressin versus octreotide and terlipressin versus vasopressin) only small, low quality studies were identified and no difference was demonstrated in any of the major outcomes. There was no difference between the terlipressin group and any of the comparison groups in the number of adverse events that caused death or withdrawal of medication.

Reviewer's conclusions: On the basis of a 34% relative risk reduction in mortality, terlipressin should be considered to be effective in the treatment of acute variceal hemorrhage. Further, since no other vasoactive agent has been shown to reduce mortality in single studies or meta-analyses, terlipressin might be the vasoactive agent of choice in acute variceal bleeding.

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Conflict of interest statement

None known. The reviewers and content expert have no permanent financial contracts with companies producing terlipressin.

Figures

1.1

1.1. Analysis

Comparison 1 Terlipressin versus placebo, Outcome 1 Mortality.

1.2

1.2. Analysis

Comparison 1 Terlipressin versus placebo, Outcome 2 Number failing initial hemostasis.

1.3

1.3. Analysis

Comparison 1 Terlipressin versus placebo, Outcome 3 Number with rebleeding.

1.4

1.4. Analysis

Comparison 1 Terlipressin versus placebo, Outcome 4 Number of procedures (tamponade, sclerotherapy, surgery or TIPS) required for uncontrolled bleeding/rebleeding.

1.5

1.5. Analysis

Comparison 1 Terlipressin versus placebo, Outcome 5 Number of blood transfusions.

1.6

1.6. Analysis

Comparison 1 Terlipressin versus placebo, Outcome 6 Adverse events causing death.

1.7

1.7. Analysis

Comparison 1 Terlipressin versus placebo, Outcome 7 Adverse events causing withdrawal of treatment.

2.1

2.1. Analysis

Comparison 2 Terlipressin versus balloon tamponade, Outcome 1 Mortality.

2.2

2.2. Analysis

Comparison 2 Terlipressin versus balloon tamponade, Outcome 2 Number failing initial hemostasis.

2.3

2.3. Analysis

Comparison 2 Terlipressin versus balloon tamponade, Outcome 3 Number with rebleeding.

2.4

2.4. Analysis

Comparison 2 Terlipressin versus balloon tamponade, Outcome 4 Number of blood transfusions.

2.5

2.5. Analysis

Comparison 2 Terlipressin versus balloon tamponade, Outcome 5 Adverse events causing death.

2.6

2.6. Analysis

Comparison 2 Terlipressin versus balloon tamponade, Outcome 6 Adverse events causing withdrawal of treatment.

3.1

3.1. Analysis

Comparison 3 Terlipressin versus endoscopic treatment, Outcome 1 Mortality.

3.2

3.2. Analysis

Comparison 3 Terlipressin versus endoscopic treatment, Outcome 2 Number failing initial hemostasis.

3.3

3.3. Analysis

Comparison 3 Terlipressin versus endoscopic treatment, Outcome 3 Number with rebleeding.

3.4

3.4. Analysis

Comparison 3 Terlipressin versus endoscopic treatment, Outcome 4 Number of procedures (tamponade, sclerotherapy, surgery or TIPS) required for uncontrolled bleeding/rebleeding.

3.5

3.5. Analysis

Comparison 3 Terlipressin versus endoscopic treatment, Outcome 5 Number of blood transfusions.

3.6

3.6. Analysis

Comparison 3 Terlipressin versus endoscopic treatment, Outcome 6 Length of hospitalization.

3.7

3.7. Analysis

Comparison 3 Terlipressin versus endoscopic treatment, Outcome 7 Adverse events causing death.

4.1

4.1. Analysis

Comparison 4 Terlipressin versus octreotide, Outcome 1 Mortality.

4.2

4.2. Analysis

Comparison 4 Terlipressin versus octreotide, Outcome 2 Number failing initial hemostasis.

4.3

4.3. Analysis

Comparison 4 Terlipressin versus octreotide, Outcome 3 Number with rebleeding.

4.4

4.4. Analysis

Comparison 4 Terlipressin versus octreotide, Outcome 4 Number of procedures (tamponade, sclerotherapy, surgery or TIPS) required for uncontrolled bleeding/rebleeding.

4.5

4.5. Analysis

Comparison 4 Terlipressin versus octreotide, Outcome 5 Number of blood transfusions.

4.6

4.6. Analysis

Comparison 4 Terlipressin versus octreotide, Outcome 6 Adverse events causing death.

4.7

4.7. Analysis

Comparison 4 Terlipressin versus octreotide, Outcome 7 Adverse events causing withdrawal of treatment.

5.1

5.1. Analysis

Comparison 5 Terlipressin versus somatostatin, Outcome 1 Mortality.

5.2

5.2. Analysis

Comparison 5 Terlipressin versus somatostatin, Outcome 2 Number failing initial hemostasis.

5.3

5.3. Analysis

Comparison 5 Terlipressin versus somatostatin, Outcome 3 Number with rebleeding.

5.4

5.4. Analysis

Comparison 5 Terlipressin versus somatostatin, Outcome 4 Number of procedures (tamponade, sclerotherapy, surgery or TIPS) required for uncontrolled bleeding/rebleeding.

5.5

5.5. Analysis

Comparison 5 Terlipressin versus somatostatin, Outcome 5 Number of blood transfusions.

5.6

5.6. Analysis

Comparison 5 Terlipressin versus somatostatin, Outcome 6 Length of hospitalization.

5.7

5.7. Analysis

Comparison 5 Terlipressin versus somatostatin, Outcome 7 Adverse events causing death.

5.8

5.8. Analysis

Comparison 5 Terlipressin versus somatostatin, Outcome 8 Adverse events causing withdrawal of treatment.

6.1

6.1. Analysis

Comparison 6 Terlipressin versus vasopressin, Outcome 1 Mortality.

6.2

6.2. Analysis

Comparison 6 Terlipressin versus vasopressin, Outcome 2 Number failing initial hemostasis.

6.3

6.3. Analysis

Comparison 6 Terlipressin versus vasopressin, Outcome 3 Number with rebleeding.

6.4

6.4. Analysis

Comparison 6 Terlipressin versus vasopressin, Outcome 4 Number of procedures (tamponade, sclerotherapy, surgery or TIPS) required for uncontrolled bleeding/rebleeding.

6.5

6.5. Analysis

Comparison 6 Terlipressin versus vasopressin, Outcome 5 Number of blood transfusions.

6.6

6.6. Analysis

Comparison 6 Terlipressin versus vasopressin, Outcome 6 Adverse events causing death.

6.7

6.7. Analysis

Comparison 6 Terlipressin versus vasopressin, Outcome 7 Adverse events causing withdrawal of treatment.

7.1

7.1. Analysis

Comparison 7 Terlipressin versus placebo (Subgroups with and without adequate cocnealment of treatment allocation), Outcome 1 Mortality.

8.1

8.1. Analysis

Comparison 8 Terlipressin versus placebo (Subgroups with and without endoscopic treatment), Outcome 1 Mortality.

9.1

9.1. Analysis

Comparison 9 Terlipressin versus placebo (Subgroups with and without nitrates), Outcome 1 Mortality.

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References

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