Assessment of propranolol in angina pectoris. Clinical dose response curve and effect on electrocardiogram at rest and on exercise.

Abstract

In a double-blind variable multidose trial ofpropranolol in angina pectoris, the maximum benefit in terms of reduced anginal pain, reduced trinitrin consumption, reduction in total duration of pain, increase in pain-free days, improvement of ST segment changes associated with ischaemia, and acute exercise tolerance, was obtained with the maximum dose of propranolol (av. dose 417 mg, range 80I-280). Progressively less benefit was seen with hal this dose, one-quarter, and one-eighth dose, though even one-eighth dose was signuficantly superior to placebo. (P=0'00028). Of these i6, I3 had greater benefit on full strength (average dose 304 mg daily) than on half strength (average dose 152 mg daily) (P = o-o2).Two other trials have used more than one dose level, but both were basically fixed dose studies as all patients received the same dosages. In one of these trials (Hebb, Godwin, and Gunton, I968), patients reported no improvement on 40 mg daily, a reduction to an average of 78 per cent ofthe attacks on placebo on 80 mg daily (P<o0o5), and on i6o mg daily tO 59 per cent of the attacks experienced on placebo tablets (P <o ooi). Mizgala, Khan, and Davies (I969) in I5 patients observed an average reduction in trinitrin consumption of 48 per cent on I6o mg daily (P < o-oi), but on doubling the dose the further reduction (I2%) was not significant.In the present study placebo and four dose levels of propranolol, adjusted to the need of each individual patient, were administered to investigate the effect of higher doses of propranolol and to examine further the hypothesis that for maximum benefit in angina the maximum tolerated dose should be given. MethodTrial design (i) Run-in period and determination of maximum dosage As with our previous trials (Gillam and Prichard, x965, i966), patients were seen for at least three

Propranolol Ameliorates Exercise‐induced Regional Myocardial Dysfunction in Dogs

“…Unquestionable set-ups using conscious, chronically instrumented animals with limited coronary reserve subjected to stress such as free run or treadmill exercise come very close to this purpose (Raberger 1985). In the present investigation a model of chronicalIy instrumented dogs with limited flow reserve, produced by filling the hydraulic oc- LED end-diastolic length; LES end-systolic length.…”

Introduction

“…Logue and Robinson deal essentially with the patient who has mild or moderately severe, stable angina pectoris. Perhaps the most important new developmnt is the use of the beta-adrenergic blocking agents, notably propranolol (Inderal).41 42 Whether other beta-blocking agents such as practolol4345 or alprenolol46 possess any significant clinical advantages is uncertain. There is uncertainty also as to the indication for propranolol in patients with infrequent pain, or even with pain two or three times daily, which subsides rapidly with rest or sublingual nitroglycerin.…”

<i>&beta;</i>-Adrenoceptor-Blocking Agents in the Management of Hypertension

“…There is some evidence that there is a considerable margin of safety with propranolol as suggested in a double-blind multi-dose level trial of propranolol in angina pectoris (Prichard and Gillam, 1971). Here the blood pressure of a group of 6 mild hypertensive patients fell from a mean 115 (154/96) (standing) to a mean of 102 (135/85) (p < 0.005) standing, as the dosage was increased from zero to an average of 320 mg daily; doubling the dose resulted in no change of blood pressure, at an average dose of 640 mg daily, the standing blood pressure averaged 103 mm Hg( 137/86).…”