Therapeutic benefit of vaso-active drugs for acute variceal bleeding: A real pharmacological effect, or a side-effect of definitions in trials?

✍ Scribed by A K Burroughs; D Patch

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 190 KB
• Volume: 24
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.510240344

✦ Synopsis

five days. The primary outcome measure was survival without rebleeding five days after sclerotherapy. Re-

DEFINITIONS IN TRIALS?

sults. After five days, the proportion of patients who had Levacher S, Letoumelin P, Pateron D, Blaise M, Lopandry survived without rebleeding was higher in the octreo-C, Pourriat J-L. Early administration of terlipressin plus tide group (85 out of 98 patients, or 87%) than in the glyceryl trinitrate to control active upper gastrointestinal placebo group [72 out of 101, or 71%; 95% confidence bleeding in cirrhotic patients. Lancet 1995;346:865-868.

interval for the difference, (range, 4% to 27%); P Å 0.009].

The mean number of units of blood transfused within ABSTRACT the first 24 hours after sclerotherapy was lower in the octreotide group (1.2 units; range, 0 to 7) than in the Upper gastrointestinal bleeding (GIB) is a major complacebo group (2.0 units; range, 0 to 10; P Å 0.006). A plication in cirrhotic patients. Endoscopy and oesophalogistic-regression analysis showed that the treatment geal sclerosis are reference treatments and must be done assignment (P Å 0.003) and the number of blood units as soon as possible. However, such treatment is not postransfused before any other treatment was undertaken sible unless the patient is admitted to hospital. In a pro-(P Å 0.002) were the only two variables independently spective, randomised, double-blind trial, we compared associated with survival without rebleeding. After adthe efficacy of terlipressin combined with glyceryl trinijustment for base-line differences between the two trate (TER-GTN), administered as early as possible to 76 groups, the odds ratio for treatment failure in the plapatients with cirrhosis who had active GIB (84 bleeding cebo group, as compared with the octreotide group, was episodes). Infusion was done at the patient's home by 3.3 [95% confidence interval, (range, 1.5 to 7.3)]. The the physician on the emergency team (a mobile intensive mean ({SD) 15-day cumulative survival rate (estimated care unit) if the patient had GIB and a history and cliniby the Kaplan-Meier method) was 38 { 12% in both cal signs of cirrhosis. Patients received either an intragroups. Side effects were minor, and their incidence was venous injection (1 to 2 mg) of TER-GTN or a doublesimilar in the two groups. Conclusions. In patients with placebo injection, and then another injection at 4 and 8 cirrhosis, the combination of sclerotherapy and octreoh. Control of bleeding, rebleeding, and mortality rate at tide is more effective than sclerotherapy alone in condays 15 and 42 were evaluated. In most patients, endostrolling acute variceal bleeding, but there is no differcopy confirmed the rupture of oesophageal varices ence between the overall mortality rates associated with (75.7%). Bleeding control was significantly better in the the two approaches to treatment. TER-GTN group (n Å 41) than in the double-placebo group (n Å 43) (P Å .034). Mortality due to bleeding epi-COMMENTS sodes was significantly lower in the TER-GTN group than in the double-placebo group at day 15 (P Å .035)

Variceal bleeding is characterised by frequent early reand at day 42 (P Å .06). There were no serious side-efbleeding, far higher than in bleeding secondary to peptic ulfects. Early administration of TER-GTN lowers the deleceration. 1,2 In addition, there is a well-recognised high morterious consequences of prolonged hypovolaemia on the tality which is related to the severity of the underlying liver hepatic function of these patients.

disease and intuitively to the severity of hemorrhage. The premise of a French group of authors was that very early Besson I, Ingrand P, Person B, Boutroux D, Heresbach D, administration of a vasoactive drug, known to be effective in Bernard P, Hochain P, et al. Sclerotherapy with or without variceal bleeding, should result in a reduction in bleeding octreotide for acute variceal bleeding. N Engl J Med and hopefully an improved survival rate. The authors chose 1995;333:555-560.

to evaluate terlipressin (a vasopressin synthetic analogue with a longer interval of action) with a protective glyceryl trinitrate patch (to obviate systemic vasoconstrictive side ef-ABSTRACT fects), versus a placebo in a double-blind randomized trial.

The trial was supported by Ferring SA, (Malmo, Sweden) the Background. Sclerotherapy is considered the most effective way to stop bleeding from esophageal varices, manufacturer of terlipressin. The patient groups (terlipressin, n Å 41; placebo, n Å 43) were very well matched according but acute variceal bleeding is still associated with a high risk of rebleeding and death. We compared sclerother-to demographic characteristics, to aetiology, and to severity of liver disease and of bleeding. The trial drug and the initial apy alone with sclerotherapy and octreotide to control acute variceal bleeding and to prevent early rebleeding resuscitative measures were administered within 60 minutes of an emergency call by a medical intensive care 'flying in patients with cirrhosis. Methods. In a double-blind, prospective trial, 199 patients with cirrhosis and acute squad'; then all the patients were taken to the same hospital.

Terlipressin 1 to 2 mg or an identical placebo was given at variceal bleeding who underwent emergency sclerother-