Beta-receptor selectivity of carvedilol and metoprolol succinate in patients with heart failure (SELECT trial): a randomized dose-ranging trial.
OBJECTIVE
To determine whether metoprolol succinate (a beta(1)-selective beta-blocker) remains beta(1)-selective compared with carvedilol (a nonselective beta-blocker) during upward titration of doses in patients with American College of Cardiology (ACC) stage C heart failure.


METHODS
Prospective, randomized, parallel-arm study. Setting. General clinical research center.


METHODS
Twenty-five beta-blocker-naïve adults with New York Heart Association functional classes II or III heart failure (i.e., ACC stage C). Intervention. Patients received either immediate-release carvedilol 3.125 mg twice/day or controlled-release metoprolol succinate 25 mg once/day; doses were titrated upward by doubling the dose every 2 weeks until reaching a maximum tolerated dose or a goal dose of carvedilol 25 mg twice/day and metoprolol 200 mg/day. Before each dose titration, terbutaline (a beta-receptor agonist) was infused at 6 mg/kg over 1 hour for determination of beta(2)-blockade.


RESULTS
Patients were studied at baseline and after each dose titration of metoprolol succinate (at 25, 50, 100, and 200 mg once/day) and immediate-release carvedilol (at 3.125, 6.25, 12.5, and 25 mg twice/day). Glucose and potassium concentrations were measured twice serially at baseline, every 10 minutes during infusion, every 15 minutes for the first hour after infusion, and every 30 minutes for the second hour after infusion. The median area under the concentration-time curve (AUC) was calculated for changes in glucose and potassium concentrations. As assessed by glucose AUC, there was no significant difference in the degree of beta(2)-blockade between metoprolol 200 mg and carvedilol 25 mg. In contrast to these data, the degree of beta(2)-blockade as assessed by potassium AUC was greater for carvedilol compared with metoprolol across all doses.


CONCLUSIONS
In this ACC stage C heart failure population, carvedilol was nonselective at all clinically relevant doses, whereas metoprolol succinate was beta(1)-selective at low doses and became progressively nonselective at higher doses.
Zebrack
James S
JS
Department of Internal Medicine, University of Utah, Salt Lake City, Utah 84112-5820, USA.
Munger
Mark
M
Macgregor
John
J
Lombardi
William L
WL
Stoddard
Gregory P
GP
Gilbert
Edward M
EM
D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects; D002227:Carbazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000077261:Carvedilol; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008875:Middle Aged; D011188:Potassium / Q000097:blood; D011412:Propanolamines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D013726:Terbutaline / Q000494:pharmacology
D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D002227:Carbazoles; D003692:Delayed-Action Preparations; D011412:Propanolamines; D000077261:Carvedilol; D008790:Metoprolol; D013726:Terbutaline; D011188:Potassium