Variability of response to beta receptor blockade for angina pectoris in clinical trials: a study of pindolol

In a randomized, controlled study we found a significant decrease in pressure-rate (double) product and an improvement in exercise tolerance in patients with angina pectoris treated with pindolol. However, when patients were observed in a long-term double-blind crossover study, pindolol treatment did not produce a significant improvement in angina pectoris or exercise tolerance over placebo. Patients treated with placebo had a gradual improvement in exercise tolerance, possibly because of the training effect of multiple treadmill tests and increased daily walking. The individual patient response to pindolol varied, with some patients showing clinical improvement and decreased double product with exercise and some having no clinical improvement despite a similar decrease in double product. Angina occurred at a lower double product with exercise, suggesting that beta receptor blockade adversely affected other variables of myocardial oxygen demand or decreased coronary blood supply. This study illustrates the difficulties with patient variability and study design that are encountered in studies of beta blocker agents for angina pectoris.