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HEART FAILURE

Lack of evidence for peripheral alpha₁- adrenoceptor blockade during long-term treatment of heart failure with carvedilol

^a Division of Cardiology, Mount Sinai Hospital and the University of Toronto, Toronto, Canada

Manuscript received April 6, 2001; revised manuscript received June 21, 2001, accepted July 13, 2001.

^* Reprint requests and correspondence to: Dr. John S. Floras, 600 University Avenue, Suite 1614, Toronto, Ontario M5G 1X5, Canada
john.floras{at}utoronto.ca

OBJECTIVES

The purpose of this study was to determine whether carvedilol’s alpha₁-adrenoceptor antagonism persists during long-term therapy of patients with congestive heart failure (CHF).

BACKGROUND

Carvedilol and metoprolol differ in that carvedilol also antagonizes beta₂- and alpha₁-adrenoceptors. We hypothesized that in contrast to metoprolol, carvedilol would increase calf vascular conductance (CVC), blunt neurally mediated vasoconstriction and attenuate neuroeffector transfer function gain.

METHODS

We randomized 36 patients with CHF (age 55 ± 1 years, ejection fraction 19 ± 1%, means ± SE) to either drug. Blood pressure (BP), heart rate, muscle sympathetic nerve activity (MSNA) and CVC were assessed before and after four months of treatment. The variability of BP and MSNA was determined using fast Fourier transformation.

RESULTS

Paired data were obtained in 23 (carvedilol, 13; metoprolol, 10) subjects. 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 maximum) increased heart rate, mean BP and MSNA. The calf vasoconstrictor response to handgrip exercise was not affected by carvedilol (from 16 ± 6 resistance U to 25 ± 10 resistance U, NS). The gain of the transfer of oscillations in MSNA into BP under resting conditions was not attenuated by carvedilol.

CONCLUSIONS

Carvedilol did not increase CVC, blunt the calf vasoconstrictor response to handgrip or attenuate the gain of the neuroeffector transfer function, indicating the absence of functionally important peripheral alpha₁-adrenoceptor antagonism during long-term treatment of CHF.

Abbreviations and Acronyms   ANOVA = analysis of variance   BP = blood pressure   CBF = calf blood flow   CHF = congestive heart failure   CVC = calf vascular conductance   CVR = calf vascular resistance   ECG = electrocardiogram   HF = high frequency   LF = low frequency   MSNA = muscle sympathetic nerve activity   VLF = very low frequency

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