Conn et al. (1) presented the results of a multicenter, randomized, double‐hlind clinical trial to assess the efficacy of propranoloi in preventing the initial hemor‐rhage from esophagogastric varices. One hundred and two patients (73 men, 29 women, mean age 54 yr) with the clinical diagnosis of cirrhosis (80 with alcoholic cirrhosis) were randomized to receive either placeho or propranoloi. The patients had endoscopically docu‐mented esophageal varices and portal hypertension, and had not hied previously from varices or from an un‐known upper gastrointestinal site. Patients with known neoplasms or severe hepatic disease or other medical conditions that might interfere with the study were excluded. Patients who agreed to undergo hepatic vein catheterization and whose hepatic vein pressure gra‐dient (HVPG) was greater than or equal to 12 mm Hg were titrated with propranoloi to reduce their HVPG to less than 12 mm Hg. After the dosage of propranoloi had heen thus determined, the patients were randomized to receive either propranoloi (51 patients) or placebo. The douhle‐blindedness of the investigation was maintained by having the patients examined at visits by nurses or fellows. The dosages were not increased dur‐ing the study. Patients returned monthly for 3 months, and every 3 months thereafter; pill counts were made and a compliance index was calculated based on the number of appointments kept, percentage of tablets consumed, propranoloi levels, alcohol consumption di‐ary, and blood alcohol levels. Heart rate was not used to measure compliance. The patients underwent endos‐copy and hepatic vein catheterization at 3 and 12 months after randomization and annually thereafter. Varices were measured endoscopically and graded according to size: grade 1, 1‐3 mm with Valsalva; grade 2, 1‐3 mm without Valsalva; grade 3,3‐6 mm; and grade 4, greater than 6 mm. Patient's Child's class was calculated using the Childs‐Turcotte criteria, with class A defined as a score of 5‐8, class B as a score of 9‐11, and class C as a score of 12‐15. The investigators used the following endpoints: 1) upper gastrointestinal hemorrhage, which was defined as hematemesis or melena that reduced hematocrit by 6% or required blood transfusions. Variceal hemorrhage was documented by endoscopic visualization of active bleeding or fresh clot or eschar on the surface of a varix in the absence of any other possible upper gastrointes‐tinal bleeding site. The examination was performed during active hemorrhage or within 24 h after bleeding stopped. The endoscopists were blinded to the patient's therapy. 2) Survival, which was expressed in number of months after randomization. The cause of death was determined in conference by the principle investigators who were unaware of the patient's therapy. 3) compli‐cations, which were defined as adverse events that may have been caused by propranolol and that necessitated stopping treatment. Decisions to stop therapy were made and recording of complications done, without knowledge of therapy. During the study period, from October 1982 to September 1986, approximately 40% of the cirrhotic patients admitted to the participating hospitals met the inclusion criteria. Of those excluded, 10% had bled before they could be assessed and ran‐domized; 20% had contraindications to /3‐blockade or were already receiving it; 15% refused either endoscopy or catheterization or declined to participate, 10% were deemed noncompliant by the investigators, and 5% had an HMPG less than 12 mm Hg. All patients were followed until the last randomized patient had been treated for at least 6 months; mean follow‐up was 16.3 ± 12 months for the placebo group and 17.1 ± 10.9 months for the propranolol group. Eleven (22%) pa‐tients of the 51 patients in the placebo group bled from varices, compared with two (4%) of the 51 patients in the propranolol group, a difference that was significant (p < 0.01, relative risk 1.4‐32.2, 95% Cl). The differ‐ence was more pronounced in patients with large var‐ices; nine of 22 patients in the placebo group bled, whereas none of 27 patients with large varices in the propranolol group bled (p < 0.001). Patients with small varices exhibited no difference between placebo and propranolol treatment; 8% bled in each group. Three patients in the placebo‐treated group bled from portal hypertensive gastropathy, whereas no patients in the propranolol group bled from this lesion. The effect of propranolol in preventing hemorrhage was confined nearly exclusively to alcoholic cirrhotics. Ten of 41 patients with alcoholic cirrhosis (24%) in the placebo group bled, compared with two of 39 patients (5%) in the propranolol group (p < 0.01). Of the nonalcoholic cirrhotics, one of 10 in the placebo group bled, whereas none of the 12 in the propranolol group bled (NS). There was no significant difference in the bleeding rate in Child's group A or C patients, although the latter group was small. Among Child's class B patients, those who received placebo bad a significantly higher rate of hemorrhage than those who received propranolol (nine of 24 vs. 1 of 11, < 0.05). Among patients who took more than 75% of their tablets, eight of 35 (23%) in the placebo group bled, whereas only two of 39 (5%) in the propranolol group hemorrhaged (p < 0.05). Among less compliant patients, there was no significant differ‐ence between groups. Survival analysis was based on intention to treat, and included all patients. There were 11 deaths (22%) in the placebo group and eight (16%) in the propranolol group (NS). Cumulative survival was slightly but not significantly improved (Kaplan‐Meier) in the propranolol group. There were three deaths from variceal bleeding in the placebo group and two in the propranolol group. Three patients in the placebo group (6%) and seven in the propranolol group (14%) suffered adverse effects requiring cessation of therapy (NS). Two patients in the propranolol group developed congestive heart failure, one developed bronchospasm, and one developed diabetes mellitus.
|Original language||English (US)|
|Number of pages||1|
|Journal||The American journal of gastroenterology|
|State||Published - Dec 1992|
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