title: Combined alpha-beta blockade (doxazosin plus metoprolol) compared with beta blockade alone in chronic congestive heart failure.
abstract: There has been growing evidence for the benefits of beta blockers, but alpha blockers have not shown sustained benefits in chronic congestive heart failure (CHF). Thirty patients with moderate to severe CHF (New York Heart Association class II to IV) were sequentially assigned to receive metoprolol 6.25 mg with the alpha-1 antagonist doxazosin 4 mg/day or metoprolol alone. The dose of metoprolol was gradually increased to a target dose of 50 mg orally twice daily. Hemodynamic measurements were obtained before drug therapy, 2 hours after the first dose of combined alpha-beta therapy or metoprolol alone, and after 3 months of continuous treatment. Nuclear ejection fraction, plasma norepinephrine, and submaximal and maximal exercise capacity were also measured before and after chronic therapy. With initial combined drug administration, mean arterial pressure, left ventricular filling pressure, and systemic vascular resistance decreased significantly compared with results after metoprolol alone. However, after 3 months of continuous therapy, both treatment groups showed similar and significant reductions in systemic vascular resistance and heart rate, with significant increases in cardiac index, stroke volume index, stroke work index, ejection fraction, and exercise capacity. Furthermore, the next dose of chronic combined medication no longer showed vasodilating effects. Chronic therapy with fixed-dose doxazosin and increasing doses of metoprolol produced identical effects as those seen in patients receiving metoprolol alone.
authors.affiliation: Cardiovascular Institute-Department of Medicine, Mount Sinai Medical Center, New York, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Kukin
authors.forename: J
authors.initials: J
authors.lastname: Kalman
authors.forename: M
authors.initials: M
authors.lastname: Mannino
authors.forename: R
authors.initials: R
authors.lastname: Freudenberger
authors.forename: C
authors.initials: C
authors.lastname: Buchholz
authors.forename: O
authors.initials: O
authors.lastname: Ocampo
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D002908:Chronic Disease; D017292:Doxazosin / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use*; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D008790:Metoprolol; D017292:Doxazosin