Beta-adrenoceptor blockade: past, present, and future.

beta-Adrenoceptor blocking drugs were originally devised as a treatment for angina pectoris. Their activity as antihypertensive agents was discovered as a result of observations made during angina trials. In the early days of study of these agents, there was a great deal of debate about the relative importance of selectivity for beta 1- and beta 2-receptors, membrane stabilising actions, and the presence or absence of partial agonist activity. It has become clear that these ancillary properties have little effect upon efficacy in angina and hypertension but they have some effect upon the adverse reactions profile. Several secondary prevention trials have established that mortality can be reduced by 25-30% in the first 2-3 years after acute myocardial infarction with drugs such as timolol and propranolol. There have been some negative trials, particularly with oxprenolol, but the pooled evidence suggests a highly significant benefit. The available primary prevention data are mainly derived from trials in hypertensive patients, who have a substantially increased risk of myocardial infarction. Overall, the hypertension trials show only a small reduction in the incidence of acute myocardial infarction, averaging about 6%. This reduction is less than would be expected from the contribution of hypertension as a risk factor for myocardial infarction. Development of new beta-adrenoceptor blocking drugs continues. Development of ancillary properties of agents derived from the labetalol structure has also attracted interest. Various combinations of beta 1-blockade, beta 2-agonist activity, and alpha-receptor blockade seem possible. After 20 years of experience, beta-blockade still presents opportunities for new developments.