HEART FAILURE
Impact of initiating carvedilol before angiotensin-converting enzyme inhibitor therapy on cardiac function in newly diagnosed heart failure
Karen Sliwa, MD, PhD*,*,
Gavin R. Norton, MD, PhD ,
Ngalulawa Kone, MD ,
Geoffrey Candy, PhD*,
John Kachope, MD*,
Angela J. Woodiwiss, PhD,
Carlos Libhaber, MD*,
Pinhas Sareli, MD* and
Rafique Essop, MD*
* Department of Cardiology, Chris-Hani-Baragwanath Hospital, Johannesburg, South Africa
Department of Chemical Pathology, Chris-Hani-Baragwanath Hospital, Johannesburg, South Africa
Department of Physiology, University of the Witwatersrand, Johannesburg, South Africa
Manuscript received March 7, 2004;
revised manuscript received May 13, 2004,
accepted May 18, 2004.
* Reprint requests and correspondence: Prof. Karen Sliwa, Department of Cardiology, Chris-Hani Baragwanath Hospital, P.O. Bertsham 2013, Johannesburg, South Africa (Email: hahnle{at}netactive.co.za).
OBJECTIVES: 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.
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Abbreviations and Acronyms
| | ACEI = angiotensin-converting enzyme inhibitor | | BB = beta-blocker | | LV = left ventricle/ventricular | | LVEDD = left ventricular end-diastolic diameter | | LVEF = left ventricular ejection fraction | | LVESD = left ventricular end-systolic diameter | | NT-pro-BNP = N-terminal pro-brain natriuretic peptide | | NYHA FC = New York Heart Association functional class |
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