The subtle differences that exist among the available beta-blocking drugs are often overlooked. Figure 3 gives a working classification. Cardioselective agents are safer than nonselective beta-blockers in diabetic patients and in those with mild-to-moderate chronic obstructive pulmo¬nary disease. This information appears to be well known worldwide. Agents with beta-agonist activity (intrinsic sympathomimetic activity, ISA) are not cardioprotective, e.g., pindolol, and should become obsolete. Of the cardio-selective agents only metoprolol has been shown in randomized clinical trials to significantly reduce coronary heart disease mortality and events. Bisoprolol has not been tried in trials of infarction patients but was beneficial in heart failure trials. Atenolol, a popular cardioselective agent, is used worldwide but has never been tested in a randomized trial of post myocardial infarction patients or in patients with left ventricular dysfunction or heart failure. It should not be assumed that this agent has similar cardioprotective properties as metoprolol, carvedilol, propranolol, bisoprolol, and timolol (see earlier discussion of clinical trials in Section IV).
Of the cardioselective agents only bisoprolol and metoprolol have been shown to decrease cardiac mortality. Both of these drugs have lipophilic properties. Lipophi-licity allows a high concentration of drug in the brain. This appears to block sympathetic discharge in the hypo-thalamus and elevate central vagal tone to a greater extent than water-soluble, hydrophilic agents. This may relate to the prevention of sudden cardiac death. Abal et al., in a rabbit model, showed that ‘‘although both metoprolol (lipophilic) and atenolol (hydrophilic) caused equal beta blockade, only metoprolol caused a reduction in sudden cardiac death.’’ It appears that this information has not reached clinicians or researchers.

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