BB vary in their gastrointestinal absorption, first-pass hepatic metabolism, lipid solubility, protein binding, body distribution, blood-brain barrier permeability, concentration in the heart, rate of hepatic biotransformation, pharmacologic activity of metabolites, and renal clearance of the drug and its metabolites. On the basis of their pharmacokinetic properties, BB can be classified into two broad categories differentiated on the basis of lipophilicity or hydrophilicity [10].

The lipid-soluble group are completely absorbed by the small intestine, metabolized by the liver and penetrate the brain easily and rapidly in high concentrations. This results in low bioavailability, substantial interpatient variability in ‘steady-state’ plasma drug concentrations, rapid elimination half-lives and the possibility of drug interactions with other drugs that affect hepatic enzymes. The blood-brain permeability may result in centrally mediated adverse effects such as vivid dreams. This group of BB is represented by propranolol, timolol, metoprolol and oxprenolol. On the contrary water-soluble BB are incompletely absorbed through the gut, are cleared, unchanged, by the kidney, and penetrate the central nervous system less easily, causing less central side-effect. They show less interpatient variation in bioavailability, have longer elimination half-lives and do not interact with drugs affecting hepatic enzymes. Atenolol, sotalol and nadolol are examples of water-soluble BB [10].

Between these two extremes, there are several drugs like betaxolol, bisoprolol and pindolol, which are cleared partly by the liver and partly by the kidney. Their clearance is only altered by severe renal or hepatic disease, and they do not appear to interact with enzyme inducers or inhibitors.

Generally, BB are well tolerated, but like most pharmacological agents they are not exempt from side effects, sometimes severe. These effects are usually manifest when high doses are used.

The two aims of the pharmacological treatment of patients with chronic SA are to improve symptoms and to prevent adverse events. The first demonstrated efficacy of BB in the clinical setting was in the early 60s, when Sir James Black, tested nethalide and proved its effectiveness in controlling symptoms of SA [3].

Subsequent studies of Prichard and Warren tested the effect of propranolol and its dose-dependent action on the treatment of SA [20, 21].

Shortly, other agents with different degrees of selectivity for beta-1 receptors, showed also improvement of symptoms, increase in exercise tolerance and a delayed onset of ST depression on the stress test compared with placebo in patients with SA [22, 23].

BB are highly effective to control exercise induced angina. They have demonstrated improvement in exercise capacity in several small placebo controlled trials, and to reduce or suppress both symptomatic and asymptomatic ischaemic episodes [5, 20, 24, 25].

No clear clinical differences have been verified, however, between different BB. Evidence has shown that the BB do not modify the threshold of rate pressure product of appearance of angina, but they delay the reaching of that stage. Decreased exercise heart rate, wall stress and myocardial contractility caused by BB keep oxygen demand below the threshold at which angina occur. The effect of reducing the rate of events in patients with SA has not been specifically studied in large trials, and most of the information comes from studies in the post-infarction period. Nevertheless, in the ASIST trial (Atenolol Silent Ischemia Study) 306 outpatients patients with Canadian Cardiovascular Society class I or II SA, and inducible ischemia were randomized to receive either atenolol (100 mg/day) or placebo during 1 year of follow-up [25].

In this trial the event-free survival (death, resuscitated ventricular arrhythmia, myocardial infarction, hospitalization for unstable angina, aggravation of angina, or revascularization) improved in atenolol-treated patients (P < 0.007), who had an prolonged time to onset of first adverse event (120 versus 79 days) and fewer total first events compared with placebo (relative risk, 0.44; 95 % confidence intervals, 0.26–0.75; P = 0.001).

The main objective of the Beta-Blocker Pooling Project was to collect and analyse data from the major long-term secondary prevention trials in order to determine whether there are subsets of post-infarction patients who benefit to a greater or lesser extent from BB therapy than the average patient population [26].

The overall, 1-year mortality, in the nine trials involving 13,679 patients analysed, was 24 % lower in the BB group compared to placebo. Subgroups in the placebo arms with high mortality (e.g. patients with a history of previous myocardial infarction, angina pectoris, mechanical or electrical complications, and digitalis usage) seemed to be particularly benefited under treatment with BB. Patients in the lower risk subgroups also appeared to benefit from BB, but this benefit was smaller in absolute terms and inconsistent across the trials. Based on these findings it is recommended to treat patients with prior myocardial infarction and SA to prevent death, especially sudden cardiac death, and myocardial infarction (Table 3.2) [27, 28].