Hemodynamic effects of alpha1-adrenoceptor antagonist, doxazosin, in patients with chronic congestive heart failure.
OBJECTIVE
Non-selective alpha-adrenoceptor antagonists have not demonstrated significant beneficial effects in chronic heart failure. Previous studies with the selective alpha1-adrenoceptor antagonist, doxazosin, led to conflicting results. We assessed the hypothesis that treatment with doxazosin adjuvant to standard oral therapy results in significant increase in cardiac index in patients with chronic heart failure.


METHODS
A double-blind, randomized study was conducted on 30 patients with chronic congestive heart failure (NYHA III-IV), with cardiac index<2.5 l/minxm, and/or with pulmonary capillary wedge pressure>16 mm Hg. Of the 30 patients, 15 were treated with doxazosin and 15 with placebo, both adjuvant to stable oral therapy, which included a minimum of an ACE inhibitor and a diuretic. Hemodynamic measurements were performed on days 1 and 2, and after 12 weeks on study medication. On day 1, patients were treated with 4 mg doxazosin or placebo. On day 2 and throughout the following 12 weeks, the patients were treated with 4 mg or 8 mg doxazosin/d (the latter, if 4 mg/d did not induce an increase >0.75 l/minxm in cardiac index), or with placebo.


RESULTS
Six patients were treated with 4 mg doxazosin/d (group A), 9 patients with 8 mg doxazosin/d (group B), and 15 with placebo. Baseline values for the cardiac index on day 1, day 2, and after 12 weeks failed to disclose significant differences between patient groups and between the days of study. On day 1, the increase in cardiac index compared with baseline was significantly higher in group A than in the placebo group (P=0.004) and group B (P=0.001). On day 2, the increase in cardiac index compared with baseline on day 1 was significantly higher in group A than in group B (P=0.003) (with reference to alpha/3=0.0167 according to Bonferroni). This was no longer observed after 12 weeks. In the placebo group, following significant changes occurred in baseline values, heart rate was lower (P=0.023) and stroke volume index was higher after 12 weeks in comparison to day 1 (P=0.032).


CONCLUSIONS
In conclusion, oral application of doxazosin supplementary to standard oral medication did not induce sustained hemodynamic benefit. Significant acute increase in cardiac index was observed in a minority (40%) of patients, whereas favorable changes in baseline hemodynamic parameters after 12 weeks occurred in the placebo group.
Kieback
Arne G
AG
Klaus-Dieter Wernecke: Institut für Medizinische Biometrie, Charité Campus Mitte, Schumannstr. 20-21, Berlin, Germany, D-10117. arne.kieback@charite.de
Rödiger
Olaf
O
Jaenecke
Halina
H
Grohmann
Andrea
A
Wernecke
Klaus-Dieter
KD
Baumann
Gert
G
Felix
Stephan B
SB
D000317:Adrenergic alpha-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D002908:Chronic Disease; D004311:Double-Blind Method; D017292:Doxazosin / Q000009:adverse effects / Q000627:therapeutic use*; D004562:Electrocardiography; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D013902:Radiography, Thoracic; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D017292:Doxazosin