Summary: When used in the treatment of hypertension propranolol is at least of similar potency to bethanidine, guanethidine, and methyldopa. Propranolol does not produce postural or exercise hypotension and it seems that it is often more acceptable to patients than conventional drugs. It usually produces the best control of the supine blood pressure.

Pronethalol, an adrenergic beta-receptor-blocking drug (Black and Stephenson, 1962), has been shown to relieve the pain of angina pectoris in a double-blind trial (Prichard, Dickinson, Alleyne, Hurst, Hill, Rosenheim, and Laurence, 1963). Its use in angina was, however, discontinued following a report of its tumour-producing activity in mice (Paget, 1963). A further disadvantage of pronethalol was that the therapeutic dose was close to that which produced side-effects.Black, Crowther, Shanks, Smith, and Dornhorst (1964) have described the pharmacology of propranolol (Inderal), a betareceptor-blocking agent in animals and man with about ten times the potency of pronethalol. It is non-carcinogenic in mice and other experimental animals. In view of the effectiveness of pronethalol it was thought that the closely related drug propranolol might be of value in angina. The present paper reports a double-blind trial in out-patients with angina pectoris. Design of TrialThe design of the trial closely followed that described by Prichard et ad. (1963). The original aim was to compare maximum tolerated doses of propranolol with placebo, but this was modified in that an upper dose limit of 100 mg. q.d.s. was later fixed ; this dose represented 40 tablets a day. During the " run-in period" the initial dosage was 10 mg. q.d.s. Increments of 10 mg. per dose per week were made up either to 100 mg. q.d.s. or to the maximum tolerated dose, when this was less. This variable dosage was selected because of the need to take into account individual variability, and also because benefit at a lower dosage might be largely a placebo effect, which may also result from increased frequency of out-patient visits. This latter factor was mitigated by having a long run-in period before the trial proper, three months or more, a period further extended owing to delay in obtaining identically tasting placebo tablets. During this time patients were seen every two weeks and the dosage was adjusted.The period of the actual trial was eight weeks. Patients were given placebo and propranolol each for two periods of two weeks' duration; they were identical in taste and appearance. Randomization of these four periods was made so that the six possible orders were achieved for every six patients admitted to the trial.Patients were considered suitable for admission to the trial if they were having at least two typical attacks of angina pectoris each week. The pain had to be of characteristic nature, site, and radiation, brought on by exertion, relieved by rest and glyceryl trinitrate, and usually lasting for one to three minutes. The purpose of the trial was explained to the patients, who were told that the new drug would be compared with identical dummy tablets in order to try to eliminate bias. Sixteen AssessmentPatients were asked to take glyceryl trinitrate for pain, but not prophylactically, and to record their attacks of angina and glyceryl trinitrate consumption on record sheets that were provided. The sheets were divided into four periods for ea...

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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

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