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The molecular evidence here briefly reviewed have reinforced the hypothesis that the changes in the ANS during HF are not merely adaptive, but rather play a direct pathogenetic role, opening novel avenues to interpret the efficacy of drugs acting by blocking β-ARs in HF.

Thus, the primary endpoint of the study was showing that initiation of therapy with bisoprolol, followed by combination therapy with enalapril after 6 months, was comparable (non-inferior) to initiation of therapy with enalapril, followed by combination therapy with bisoprolol, after 6 months, with respect to the prevention of all-cause death and all-cause hospitalizations ().

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Fifty-three patients were excluded from randomization because they were already taking a beta-blocker, and eight were excluded because they had extensive wall-motion abnormalities either at rest or during stress testing.

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Subjects received 10 mg bisoprolol, 50 mg carvedilol, 10 mg nebivolol and placebo on the first morning followed by 5 mg bisoprolol once daily, 25 mg carvedilol twice daily, 5 mg nebivolol once daily and placebo for 1 week.

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