Abstract ID : 111389
 

Effects of Carvedilol on the Renin-Angiotensin-Aldosterone System in Patients with Ischaemic Left Ventricular Systolic Dysfunction

J GF Cleland
Authors: G Murray; P W Macfarlane; D J Pennell; A Lahiri; S Ray; J Dalle Mule; Z Vered; J G Cleland

Background: Beta-blockers, in synergy with ACE inhibitors, are an effective therapy for patients with heart failure secondary to left ventricular (LV) systolic dysfunction but the mechanism(s) of action remain unclear. Part of their benefits may be due to suppression of renin, thereby enhancing the efficacy of ACE inhibitors. We measured changes in renin and aldosterone in response to carvedilol in the CHRISTMAS (The Carvedilol Hibernation Reversible Ischaemia Trial; Marker of Success) study.

Methods: Patients with chronic heart failure of ischaemic aetiology were screened by echo for systolic dysfunction (corresponding to a LVEF of <=39%). Eligible patients were further assessed by myocardial perfusion imaging, radionuclide ventriculography and measurement of renin activity and aldosterone. Hibernation was defined as a regional mismatch of impaired echo wall motion with preserved myocardial perfusion. All imaging data were assessed in a blinded fashion by core laboratories. Patients were then randomised to receive placebo or carvedilol in a double-blind fashion, titrated to a target dose of 25 mg bid (50 mg bid if >=85 kg) or matching placebo. Patients were reassessed approximately 6 months after randomisation.

Results: 305 patients were randomised and included in the intention to treat population, of whom 242 had renin activity and 188 had aldosterone measured. Baseline levels of renin and aldosterone were similar on carvedilol and placebo and in patients designated as hibernators and non-hibernators. Mean LVEF rose on carvedilol compared to placebo (+2.8±0.7% v -0.4±0.7%; p=0.0001). Plasma renin activity tended to fall on carvedilol compared to placebo (median change and [inter-quartile range](-38µU/mL[-165 to -1] v +2µU/mL[-48 to 76]; p=0.054 but not aldosterone (-0.05nmol/L[-0.17 to +0.06] v 0.0nmol/L[-0.12 to +0.09].

Conclusions: Carvedilol may reduce plasma renin activity when administered to patients with heart failure and LV systolic dysfunction treated with ACE inhibitors but this does not lead to a further suppression of aldosterone.