Clinical Evaluation of Human Amnion Tissue Culture
Authors: E. G. Jonas, A. E. Caunt
Journal: BMJ (1965)

Angina Pectoris-Keelan MBEICTJSNH used fewer tablets on placebo than on the drug, and one used equal numbers in both periods.This result is statistically highly significant (P<0.01).Seven patients had improved pain-free effort tolerance while on the drug; there was no difference between the two periods in the other 12 patients.This is statistically significant (P<0.04).Slowing of the resting heart rate was often noted while patients were receiving propranolol.The mean heart rate of the 19 patients on the drug was 63; on placebo it was 78.There was some correlation between bradycardia and decrease in frequency of anginal attacks.Slowing of heart rate was noted in 15 patients while on propranolol; this was associated with decreased frequency of angina in 12.No alteration in the heart rate was noted in the other four patients ; only one of these (Case 12) showed a reduced frequency of attacks.Eighteen patients were normotensive.Fall in blood-pressure while taking propranolol was recorded in only one of these.The remaining patient (Case 15) was hypertensive (B.P.200/ 100).While taking propranolol the tension dropped to 200/80.No change in blood picture or S.G.P.T. or evidence of albuminuria was found in any of the patients.Similarly, there was no change in the body weight or electrocardiogram.No patient developed evidence of cardiac failure during the trial.Apart from dizziness in one patient there were no side-effects. DiscussionIt was suggested by Black and Stephenson (1962) that specific beta-receptor blockade might be beneficial in angina pectoris, because of reduction in the oxygen requirements of cardiac muscle.This hypothesis is supported by the results of the present trial, which show, in addition to reduction in number of anginal attacks and consumption of glyceryl trinitrate tablets, improvement in pain-free effort tolerance.There is one other report of a double-blind trial of propranolol in angina of effort (Srivastava et al., 1964) in the literature.A series of 20 patients were given propranolol 20 mg.t.i.d. for three weeks and placebo for a further three weeks.No significant difference between drug and placebo was found.It is possible that the smaller dose of propranolol used may have been subtherapeutic.In this context it is relevant that slowing of the heart rate was not observed in any patient during the trial.This suggests that effective blockade of myocardial adrenergic beta-receptors was not achieved.Improved exercise tolerance following intravenous injection of propranolol in patients previously limited by angina has been reported recently (Hamer et al., 1964).The same authors found that beta-adrenergic blockade reduced the heart rate at all levels of exercise, but Bishop and Segel (1963) and Chamberlain and Howard (1964) have shown that the cardiac output on exercise in the erect position is maintained.From preliminary investigation of propranolol it seems likely that intestinal absorption is incomplete and variable (S. A. Stephen, personal communication, 1964).Therefore it may be that some patients will require larger doses than those prescribed in this trial.It is proposed to restudy, using larger doses of propranolol, those patients who did not respond to 30 mg. t.i.d. SummaryA double-blind trial of propranolol has been carried out on 19 patients suffering from angina of effort.The drug was found to be significantly better than placebo in reducing the frequency of attacks of angina pectoris and the number of glyceryl trinitrate tablets taken, and in improving pain-free effort tolerance.