Lack of evidence for peripheral alpha(1)-adrenoceptor blockade during long-term treatment of heart failure with carvedilol

OBJECTIVES The purpose of this stud), was to determine whether carvedilol's alpha(1)-adrenoceptor antagonism persists during long-term therapy of pati ents with congestive heart failure (CHF). BACKGROUND Carvedilol and metoprolol differ in that carvedilol also antagon izes beta(2)- and alpha(1)-adrenoceptors. We hypothesized that in contrast to metoprolol, carvedilol would increase calf vascular conductance (CVC), b lunt neurally mediated vasoconstriction and attenuate neuroeffector transfe r function gain. METHODS We randomized 36 patients with CHF (aged 55 +/- 1 years, ejection f raction 19 +/- 1%, means +/- SE) to either drug. Blood pressure (BP), heart rate, muscle sympathetic nerve activity (MSNA) and CVC were assessed befor e and after four months of treatment. The variability of BP and MSNA was de termined using fast Fourier transformation. RESULTS Paired data were obtained in 23 (carvedilol, 13; metoprolol, 10) su bjects. Both beta-blockers decreased heart rate, but neither affected mean BP or CVC (carvedilol: 0.016 +/- 0.002 to 0.018 +/- 0.003 U; metoprolol: 0. 020 +/- 0.002 to 0.020 +/- 0.004 U). Isometric handgrip exercise (30% of ma ximum) increased heart rate, mean BP and MSNA. The calf vasoconstrictor res ponse to handgrip exercise was not affected by carvedilol (from 16 +/- 6 re sistance U to 25 +/- 10 resistance U, NS). The gain of the transfer of osci llations in MSNA into BP under resting conditions was not attenuated by car vedilol. CONCLUSIONS Carvedilol did not increase CVC, blunt the calf vasoconstrictor response to handgrip or attenuate the gain of the neuroeffector transfer f unction, indicating the absence of functionally important peripheral alpha( 1)-adrenoceptor antagonism during long-term treatment of CHF. (J Am Coll Ca rdiol 2001;38:1463-9) (C) 2001 by the American College of Cardiology.