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Randomised trial of transjugular-intrahepatic-portosystemic shunt versus endoscopy plus propranolol for prevention of variceal rebleeding. The transjugular-intrahepatic-portosystemic shunt is a new interventional treatment for portal hypertension. The aim of our study was to compare the transjugular shunt with endoscopic treatment for the prophylaxis of recurrent variceal bleeding.Between March, 1993, and March, 1996, 126 patients with variceal bleeding were randomly assigned either (...) transjugular shunt (n = 61) or endoscopic treatment (n = 65). Patients were followed up for a median of 14 (IQR 8-25) months and 13 (8-25) months, respectively. In 31 (51%) of the shunted patients, simultaneous transjugular-variceal embolisation was done at the time of shunt placement. Endoscopic treatment consisted of sclerotherapy and/or banding ligation and was combined with propranolol medication.Technical success was achieved in all patients assigned to the shunt group. During follow-up
Propranolol and sclerotherapy in the prevention of gastrointestinal Rebleeding in patients with cirrhosis: a meta-analysis Propranolol and sclerotherapy in the prevention of gastrointestinal Rebleeding in patients with cirrhosis: a meta-analysis Propranolol and sclerotherapy in the prevention of gastrointestinal Rebleeding in patients with cirrhosis: a meta-analysis Bernard B, Lebrec D, Mathurin P, Opolon P, Poynard T Authors' objectives To assess the efficacy of the beta-blocker propranolol (...) (RCTs). In addition, the studies had to be published as an abstract or article; include patients with cirrhosis and oesophageal varices, patients enrolled after initial rebleeding from oesophageal varices, and patients in whom bleeding was not treated with sclerotherapy; a comparison of propranolol with endoscopic sclerotherapy; have a mean follow-up of more than 11 months; and have at least one of the previously mentioned end points. Specific interventions included in the review Propranolol
Propranolol in prevention of recurrent bleeding from severe portal hypertensive gastropathy in cirrhosis. The two main causes of gastrointestinal bleeding in cirrhosis are oesophageal varices and portal hypertensive gastropathy (PHG). Rebleeding from varices can be prevented by beta-blockers, but it is not clear whether these drugs effectively reduce rebleeding from PHG. 54 cirrhotic patients with acute or chronic bleeding from severe PHG took part in a randomised, controlled trial (...) to investigate the efficacy of propranolol in prevention of rebleeding from PHG. 26 patients were randomised to receive propranolol daily at a dose that reduced the resting heart rate by 25% or to 55 bpm (20-160 mg twice daily), throughout mean follow-up of 21 (SD 11) months. 28 untreated controls were followed-up, with the same examinations, for 18 (13) months. The actuarial percentages of patients free of rebleeding from PHG were significantly higher in the propranolol-treated patients than
Long term propranolol treatment and changes in body weight after myocardial infarction. To determine the effect of long term propranolol treatment on body weight.Retrospective analysis of data from a placebo controlled randomised double blind clinical trial (the beta blocker heart attack trial).3837 Men and women randomised 5-21 days after an acute myocardial infarction to treatment with placebo or propranolol for up to 40 months. Patients were followed up at annual visits.Changes in body (...) weight.At the first annual visit patients treated with propranolol had gained more weight than those given placebo (mean weight gain 2.3 kg v 1.2 kg respectively, mean difference 1.2 kg (95% confidence interval 0.9 to 1.5]. These group differences remained at the second and third annual visits. The difference in weight gain could not be explained by discrepancies in the use of diuretics or in physical activity and was similar in patients of both sexes and of all ages.Long term beta blockade results
Controlled trial of propranolol to prevent recurrent variceal bleeding in patients with non-cirrhotic portal fibrosis. Fifty patients with non-cirrhotic portal fibrosis who were admitted to hospital because of upper gastrointestinal bleeding were randomly assigned to treatment with either oral propranolol given in doses that reduced the resting pulse rate by 25% (25 patients) or with a placebo (25 patients). One year after the start of the study 20 patients in the propranolol group and five (...) patients in the placebo group were free from recurrent gastrointestinal bleeding (p less than 0.0001). Giving continuous oral propranolol treatment is therefore effective in preventing recurrent upper gastrointestinal bleeding in patients with non-cirrhotic portal fibrosis.
Propranolol in the prevention of first upper gastrointestinal tract hemorrhage in patients with cirrhosis of the liver and esophageal varices. We conducted a prospective, randomized, multicenter, single-blind trial of propranolol as compared with placebo in the prevention of first upper gastrointestinal tract bleeding in patients with cirrhosis of the liver. A total of 230 patients (90 percent with alcoholism and 46 percent with a Child-Pugh grade C classification) with large esophageal varices (...) without previous bleeding were randomly assigned to receive either propranolol (n = 118) or placebo (n = 112), after they had been divided into two groups according to the severity of their liver disease. The end points of the study were bleeding and death. The dose of propranolol was progressively increased to decrease the heart rate by 20 to 25 percent. The final doses were 40 mg of conventional propranolol and 160 and 320 mg of long-acting propranolol daily in 22 percent, 60 percent, and 18 percent
A comparison of verapamil and propranolol for the initial treatment of hypertension. Racial differences in response. We compared verapamil and propranolol hydrochloride for monotherapy of hypertension. Verapamil lowered blood pressure (BP) more effectively than propranolol in black and white patients. Verapamil was equally effective in blacks and whites, whereas propranolol was more effective in whites. Heart rate was reduced by 6.0 beats per minute by verapamil, and by 13.6 beats per minute (...) by propranolol. In blacks, verapamil lowered systolic BP 16.9 vs 8.1 mm Hg for propranolol; verapamil reduced diastolic BP 12.8 vs 8.6 mm Hg for propranolol. In whites, verapamil lowered systolic BP 19.0 vs 12.7 mm Hg for propranolol; verapamil reduced diastolic BP 16.7 vs 12.3 mm Hg for propranolol. Increases in systolic BP were observed in 22% and 3.4% of patients receiving propranolol and verapamil, respectively. The PR interval was increased from 163.5 to 174.9 ms for verapamil vs 160.3 to 164.4 ms
Aggravation by propranolol of hyperglycaemic effect of hydrochlorothiazide in type II diabetics without alteration of insulin secretion. 14 hypertensive men with type II diabetes sequentially received, in random order, hydrochlorothiazide 50 mg twice a day, propranolol 80 mg twice a day, and both drugs in combination. The 3-week treatment periods were separated by a 1-week washout period. Hydrochlorothiazide significantly increased fasting glucose by 31% (p less than 0.05) and glycosylated (...) haemoglobin (HbA1c) by 6.0% (p less than 0.10). A similar treatment period of propranolol 80 mg twice a day caused no significant increases. However, when both drugs were taken in combination, fasting glucose rose by 56% and HbA1c by 14.7% (p less than 0.01). The hyperglycaemic effect of hydrochlorothiazide and its potentiation by propranolol were independent of serum potassium and of endogenous insulin secretion as measured by urine C-peptide excretion. The combination of hydrochlorothiazide
Therapeutic effect of propranolol on paradoxical hypertension after repair of coarctation of the aorta. Patients undergoing repair of coarctation of the aorta often have self-limited but severe hypertension in the first week after surgery (paradoxical hypertension). We conducted a controlled trial of treatment with propranolol before repair of coarctation of the aorta in 14 children to determine whether the drug would prevent paradoxical hypertension. Seven patients were randomly assigned (...) to receive propranolol for two weeks before surgery and throughout the first postoperative week, and seven patients were assigned to receive standard postoperative care. Both groups had a similar significant (P less than 0.05) increase in the plasma norepinephrine level in response to surgery; however, when compared with no treatment, treatment with propranolol reduced not only the rise in systolic (P = 0.004) and diastolic (P = 0.003) blood pressure but also the postoperative increase in plasma renin
Influence of propranolol on weight and salt and water homoeostasis in chronic liver disease. Sixteen patients with chronic liver disease were treated with propranolol or placebo in a double-blind study. Skinfold thickness, total body water and exchangeable sodium, and urinary sodium were measured every 6 months for a year; body weight was measured every 2 (later every 3) months for 15 months. Propranolol treatment was associated with a significant rise in body weight after 9 months (...) and significant rises in skinfold thickness and body fat after 12 months. Propranolol-treated patients showed a fall in total body water at 6 months and a rise in urinary sodium concentration at 12 months. They did not show the rise in total body exchangeable sodium that occurred in placebo-treated patients. Propranolol seems to affect salt and water homoeostasis favourably in patients with chronic liver disease.
Prevention of ventricular fibrillation during acute myocardial infarction by intravenous propranolol. A trial of intravenous followed by oral propranolol, started within 4 h of onset of suspected myocardial infarction and continued over 27 h, was carried out in 735 patients; 364 received propranolol, 371 were controls. Ventricular fibrillation during the first 48 h after entry to the trial occurred in 2 treated patients and in 14 controls (p = 0.006). Rates of hospital mortality, complications (...) other than ventricular fibrillation, and progression from threatened to completed infarction did not differ between treated and control patients. Ventricular fibrillation was not apparently prevented by prior beta-blocker treatment, which was not a reason for exclusion from the trial. This intravenous/oral propranolol regimen seems to prevent ventricular fibrillation due to evolving myocardial infarction.
Effect of propranolol on myocardial-infarct size in a randomized blinded multicenter trial. A multicenter randomized single-blind study was performed to evaluate the effects of propranolol administered during the evolution of myocardial infarction. Five centers enrolled a total of 269 patients, with 134 receiving propranolol and 135 placebo. Propranolol or placebo was given intravenously upon randomization (0.1 mg per kilogram of body weight) and then orally for nine days to keep the heart rate (...) between 45 and 60 beats per minute. Less than 2 per cent of patients were treated within 4 hours after the onset of symptoms, but 50 per cent received therapy within 8 hours of onset of chest pain, and the remainder between 8 and 18 hours. The heart rates in the propranolol-treated group were significantly lower than those in the placebo group (P less than 0.001). Base-line characteristics, including the mean heart rate (79.6 vs. 81.3) and the left ventricular ejection fraction (49.0 vs. 49.5), were
Cigarette smoking and the treatment of angina with propranolol, atenolol, and nifedipine. To determine whether cigarette smoking affects the results of drug treatment for angina, we studied 10 cigarette smokers with angina who were given placebo, nifedipine (60 mg per day), propranolol (240 mg per day), and atenolol (100 mg per day), each for one week. The four-week double-blind study was repeated with the same randomly determined order of drug sequences, after all 10 subjects had stopped (...) the results of 48-hour ambulatory monitoring remained unchanged. The improvement after patients stopped smoking was greater during treatment with nifedipine than during administration of the other two drugs or placebo. Blood levels of propranolol were increased when patients stopped smoking; levels of nifedipine and atenolol were unchanged. Our data show that smoking had direct and adverse effects on the heart and interfered with the efficacy of all three anti-anginal drugs, but with nifedipine the most.
Controlled trial of propranolol for the prevention of recurrent variceal hemorrhage in patients with cirrhosis. We conducted a prospective randomized trial of propranolol for the prevention of recurrent variceal bleeding in 48 patients with cirrhosis of the liver. During a follow-up period of up to 21 months, 12 of 26 patients in the propranolol group and 11 of 22 in the control group had rebleeding from esophageal varices. There was no significant difference in rebleeding between the two (...) groups. This contrasts with a previous report of the efficacy of propranolol in preventing recurrent gastrointestinal bleeding in alcoholic cirrhosis. The difference in results may be due to the inclusion in our study of patients with other causes of cirrhosis and more severe liver disease. Propranolol may not be indicated for the prophylaxis of variceal rebleeding in such patients, and we advocate that its use be limited at present to controlled clinical trials.
A randomized trial of propranolol in patients with acute myocardial infarction. II. Morbidity results. The beta-Blocker Heart Attack Trial (BHAT) was a placebo-controlled, randomized, double-blind clinical trial of the long-term administration of propranolol hydrochloride to persons who had had at least one confirmed myocardial infarction. Among 3,837 patients followed up for an average of 25 months, coronary incidence, defined as recurrent nonfatal definite reinfarction plus fatal coronary (...) heart disease, in the propranolol group was 10.0%, compared with 13.0% in the placebo group, a reduction of 23%. The incidence of definite nonfatal reinfarction was lower by 15.6%, and that of definite or probable nonfatal reinfarction by 14.7%. Among patients with a history of congestive heart failure (CHF), 14.8% of the propranolol-treated patients experienced definite CHF during the study, as did 12.6% of the placebo-treated patients. Among patients without history of CHF, the percentages
Anti-platelet activity of beta-adrenergic antagonists: inhibition of thromboxane synthesis and platelet aggregation in patients receiving long-term propranolol treatment. Treatment of hypertensive patients with dl-propranolol (640 mg/day) significantly inhibited thromboxane synthesis by their platelets and platelet aggregation induced by thrombin or arachidonic acid. The effects were dose-related and were also caused by the stereoisomer, d-propranolol (640 mg/day), which has very little beta (...) -blocking activity. These findings suggest that the cardioprotective effects of propranolol may be due partly to this anti-platelet activity, to a reduction in thromboxane-induced coronary-artery vasoconstriction, or to both. d-Propranolol treatment may be particularly useful, since this isomer provides similar benefits without causing pronounced beta-adrenergic blockade.
Comparison of propranolol and hydrochlorothiazide for thr initial treatment of hypertension. I. Results of short-term titration with emphasis on racial differences in response. Veterans Administration Cooperative Study Group on Antihypertensive agents. We compared hydrochlorothiazide and propranolol hydrochloride for monotherapy of hypertension by a double-blind study of 683 men who were titrated to less than 90 mm Hg diastolic BP or to 640 mg of propranolol or 200 mg of hydrochlorothiazide (...) . Propranolol reduced systolic BP from 146.0 +/- 14.4 (SD) to 134.8 +/- 16.3 mm Hg and diastolic BP from 101.6 +/- 4.6 to 90.5 +/- 7.5 mm Hg. Hydrochlorothiazide lowered both systolic BP more effectively from 146.5 +/- 15.8 to 128.8 +/- 12.2 mm Hg and diastolic BP from 101.3 +/- 4.5 to 89.4 +/- 6.5 mm Hg. In blacks, hydrochlorothiazide lowered systolic BP 20.3 +/- 14.3 mm Hg v 8.2 +/- 12.2 mm Hg for propranolol; hydrochlorothiazide reduced diastolic BP 13.0 +/- 7.0 mm Hg v 9.5 +/- 7.0 for propranolol
Comparison of propranolol and hydrochlorothiazide for the initial treatment of hypertension. II. Results of long-term therapy. Veterans Administration Cooperative Study Group on Antihypertensive Agents. As described in the preceding communication, either propranolol hydrochloride or hydrochlorothiazide were randomly allocated in a double-blind manner to 683 patients with initial diastolic BP in the range of 95 to 114 mm Hg. Of this number, 394 entered the long-term treatment phase. During (...) the subsequent 12 months of long-term treatment, hydrochlorothiazide was more effective than propranolol in controlling BP (mean reductions, -17.5/-13.1 mm Hg with hydrochlorothiazide compared with -8.3/-11.3 with propranolol. After treatment with hydrochlorothiazide, a greater percentage of patients achieved the goal diastolic BP of less than 90 mm Hg (65.5% compared with 52.8% taking propranolol). Also during treatment, fewer patients receiving hydrochlorothiazide required termination as compared
A randomized trial of propranolol in patients with acute myocardial infarction. I. Mortality results. The beta-Blocker Heart Attack Trial (BHAT) was a National Heart, Lung, and Blood Institute-sponsored, multicenter, randomized, double-blind, and placebo-controlled trial designed to test whether the regular administration of propranolol hydrochloride to men and women who had experienced at least one myocardial infarction would result in a significant reduction in total mortality during a two (...) - to four-year period. During a 27-month interval, 3,837 persons between the ages of 30 and 69 years were randomized to either propranolol (1,916 persons) or placebo (1,912 persons), five to 21 days after the infarction. Depending on serum drug levels, the prescribed maintenance dose of propranolol hydrochloride was either 180 or 240 mg/day. The trial was stopped nine months ahead of schedule. Total mortality during the average 24-month follow-up period was 7.2% in the propranolol group and 9.8
Benzodiazepine withdrawal symptoms and propranolol. 40 patients seen in general practice and psychiatric outpatient clinics who had taken lorazepam or diazepam alone in regular dosage for a mean period of 3.6 years had their benzodiazepine replaced by propranolol (60--120 mg/day) or placebo for two weeks under double-blind conditions. Depending on the criteria for the definition of an abstinence syndrome, 27--45% of the patients had withdrawal symptoms during the study. Propranolol did