Impact of initiating carvedilol before angiotensin-converting enzyme inhibitor therapy on cardiac function in newly diagnosed heart failure.
OBJECTIVE
The purpose of this research was to evaluate the therapeutic value of initiating a beta-blocker before an angiotensin-converting enzyme inhibitor (ACEI) in the treatment of heart failure.


BACKGROUND
Although ACEI and carvedilol produce benefits in heart failure, whether the order of initiation of therapy determines the impact on left ventricular (LV) function and New York Heart Association functional class (NYHA FC) has not been determined.


METHODS
A single-center, prospective, randomized, open-label study was performed. We evaluated whether initiation of therapy with carvedilol either before (n = 38) or after (n = 40) perindopril therapy in newly diagnosed patients in NYHA FC II to III heart failure with idiopathic dilated cardiomyopathy, with the addition of the alternative agent after six months, determined subsequent changes in NYHA FC and LV function (echocardiography and radionuclide ventriculography). Study drugs were titrated to maximum tolerable doses.


RESULTS
There were no differences in baseline characteristics between the study groups. After 12 months 11 patients died (6 in the group where the ACEI was initiated). At 12 months the group receiving carvedilol as initial therapy achieved a higher tolerable dose of carvedilol (43 +/- 17 mg vs. 33 +/- 18 mg, p = 0.03); a lower dose of furosemide (p < 0.05); and better improvements in symptoms (NYHA FC, p < 0.002), LV ejection fraction (radionuclide: 15 +/- 16% vs. 6 +/- 13%, p < 0.05; echocardiographic, p < 0.01), and plasma N-terminal pro-brain natriuretic peptide concentrations (p < 0.02).


CONCLUSIONS
As opposed to the conventional sequence of drug use in the treatment of heart failure, initiation of therapy with carvedilol before an ACEI results in higher tolerable doses of carvedilol and better improvements in FC and LV function.
Sliwa
Karen
K
Department of Cardiology, Chris-Hani-Baragwanath Hospital, Johannesburg, South Africa.
Norton
Gavin R
GR
Kone
Ngalulawa
N
Candy
Geoffrey
G
Kachope
John
J
Woodiwiss
Angela J
AJ
Libhaber
Carlos
C
Sareli
Pinhas
P
Essop
Rafique
R
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002227:Carbazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D000077261:Carvedilol; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000097:blood / Q000187:drug effects; D010446:Peptide Fragments / Q000097:blood / Q000187:drug effects; D011412:Propanolamines / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D013318:Stroke Volume / Q000187:drug effects; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002227:Carbazoles; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D011412:Propanolamines; C109794:pro-brain natriuretic peptide (1-76); D000077261:Carvedilol; D020097:Natriuretic Peptide, Brain