A comparison of nine calcium ion antagonists and propranolol: Exercise tolerance, heart rate and ST-segment changes in patients with chronic stable angina pectoris

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Abstract
The effects of nine calcium ion antagonists on exercise tolerance, heart rate and ST-segment changes were compared with those of propranolol in two hundred and eighty patients with established chronic stable angina pectoris. These patients participated in clinical trials for anti-anginal efficacy against placebo, using identical methods and similar protocols, but the comprison reported here was retrospective. The trials were all fixed dose, and the dose was determined by previous upward titration to arrive at an average maximal tolerance level. All the drugs except prenylamine increased the exercise tolerance significantly when compared with placebo. Maximal ST-segment depression on exercise was reduced during treatment with propranolol while treatment with the calcium ion antagonists had no significant effect. The time to the development of 1 mm ST-segment depression was prolonged by all the drugs. Nifedipine, PY-108-068 and nicardipine increased the resting heart rate whereas verapamil, diltiazem, gallopamil, KB-944, prenylamine and tiapamil produced a slight reduction. Propranolol produced a highly significant reduction in the resting and maximal heart rates and the rate-pressure product, whereas gallopamil increased the rate-pressure product by +8% and prenylamine reduced it by-10%. At the doses used, diltiazem, gallopamil and verapamil produced a greater increase in exercise tolerance than did propranolol, while the other drugs were inferior. None of the calcium ion antagonists matched the increase in the time taken to develop 1 mm ST-segment depression with propranolol, although the results with verapamil and gallopamil were close. The calcium ion antagonists are effective antianginal agents which produce their effects by mechanisms which are very different to the beta-adrenoreceptor blocking agents.