Key result
Starting carvedilol before perindopril yields ~9-point greater LVEF improvement than starting perindopril first.
Why the study?
Although ACEI and carvedilol both benefit heart failure patients, whether the order of initiating these therapies determines their impact on LV function and NYHA functional class had not been determined.
Does initiating carvedilol before perindopril improve NYHA functional class and left ventricular function compared to initiating perindopril before carvedilol in newly diagnosed patients with NYHA class II to III heart failure and idiopathic dilated cardiomyopathy?
RCT (n=78)
Open-label
Randomized
No
Does initiating carvedilol before perindopril improve NYHA functional class and left ventricular function compared to initiating perindopril before carvedilol in newly diagnosed patients with NYHA class II to III heart failure and idiopathic dilated cardiomyopathy?
Initiating beta-blocker therapy with carvedilol prior to an ACE inhibitor in newly diagnosed idiopathic dilated cardiomyopathy patients leads to higher achieved carvedilol doses and superior improvements in left ventricular ejection fraction and symptom class at 12 months.
Answers are grounded in this paper and cite their sources.
Starting beta-blocker before ACEI may improve LV function in HF; leaves open optimal sequencing in randomized trials.
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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Sliwa et al. (2004) conducted an RCT in Newly diagnosed NYHA class II to III heart failure with idiopathic dilated cardiomyopathy (n=78). Carvedilol initiated before perindopril (with perindopril added after 6 months) vs. Perindopril initiated before carvedilol (with carvedilol added after 6 months; achieved carvedilol dose 33 ± 18 mg) was evaluated on Change in left ventricular ejection fraction (radionuclide ventriculography) and NYHA functional class at 12 months (p=<0.05). Initiating carvedilol before perindopril improved LVEF more than initiating perindopril first and improved functional class at 12 months.
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