BETA-BLOCKERS IN HEART-FAILURE - A COMPARISON OF A VASODILATING BETA-BLOCKER WITH METOPROLOL

Objective-To determine whether a third generation vasodilating beta bl ocker (celiprolol) has long term clinical advantages over metoprolol i n patients with chronic heart failure. Design-A double blind placebo c ontrolled randomised trial. Setting-University teaching Hospital. Pati ents-50 patients with stable chronic heart failure (NYHA class II-IV) due to idiopathic dilated, ischaemic, or hypertensive cardiomyopathy, with left ventricular ejection fraction < 0.45. Interventions-Celiprol ol 200 mg daily (n = 21), metoprolol 50 mg twice daily (n = 19), or pl acebo (n = 10) for three months with a four week dose titration period . After the double blind period, patients entered an open label study (with placebo group receiving beta blockers) and were assessed after o ne year. Main outcome measures-Clinical response, efficacy, and tolera nce were assessed by the Minnesota heart failure symptom questionnaire , six minute walk test, Doppler echocardiography (systolic and diastol ic function), radionuclide ventriculography, and atrial and brain natr iuretic peptides measured at baseline and after three months. Results- In the metoprolol group at 12 weeks v baseline there was a 47% reducti on in symptom score (p < 0.001), improvement of NYHA class (mean (SEM) , 2.6 (0.12) to 1.9 (0.13), p = 0.001), exercise distance (1246 (54) t o 1402 (52) feet, p < 0.001), and left ventricular ejection fraction ( 26.9 (3.1)% to 31 (3.0)%, p = 0.016), and a fall in heart rate (restin g, 79 (3) to 62 (3) beats/min, p < 0.001). In the celiprolol group the re was a 38% reduction in symptom score (p = 0.02), less improvement i n exercise distance (1191 (55) to 1256 (61) feet, p = 0.05), and no si gnificant changes in NYHA. class, left ventricular ejection fraction, or heart rate. Mortality at one year was 11% in metoprolol and 19% in the celiprolol group, and symptomatic improvement was maintained in th e survivors. Conclusions-Both drugs were well tolerated but the vasodi lator properties of celiprolol do not seem to provide any obvious addi tional benefit in the long term treatment of heart failure.