title: Angiotensin receptor antagonists to prevent sudden death in heart failure: does the dose matter?
abstract: International guidelines recommend ICD implantation in patients with severe left ventricular dysfunction of any origin only after careful optimization of medical therapy. Indeed, major randomized clinical trials suggest that suboptimal use of fundamental drugs, such as ACE inhibitors (ACE-i) and beta-blockers, may affect ICD shock-free survival, sudden cardiac death (SCD), and overall mortality. While solid evidence in favour of pharmacological therapy based on ACE-i with or without beta-blockers is available, data on SCD in HF patients treated with angiotensin receptor blockers (ARBs) are limited. The present paper systematically analyses the impact of ARBs on SCD in HF and reviews the contributory role of the renin-angiotensin system (RAS) to the establishment of arrhythmic substrates. The following hypothesis is supported: (1) the RAS is a critical component of the electrical remodelling of the failing myocardium, (2) RAS blockade reduces the risk of SCD, and (3) ARBs represent a powerful tool to improve overall survival and possibly reduce the risk of SCD provided that high doses are employed to achieve optimal AT1-receptor blockade.
authors.affiliation: Cardiology, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University, Via di Grottarossa 1035-39, 00189 Rome, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Francia
authors.affiliation: Cardiology, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University, Via di Grottarossa 1035-39, 00189 Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Palano
authors.affiliation: Cardiology, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University, Via di Grottarossa 1035-39, 00189 Rome, Italy.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Tocci
authors.affiliation: Cardiology, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University, Via di Grottarossa 1035-39, 00189 Rome, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: Adduci
authors.affiliation: Cardiology, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University, Via di Grottarossa 1035-39, 00189 Rome, Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Ricotta
authors.affiliation: Cardiology, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University, Via di Grottarossa 1035-39, 00189 Rome, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Semprini
authors.affiliation: Cardiology, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University, Via di Grottarossa 1035-39, 00189 Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Caprinozzi
authors.affiliation: Cardiology, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University, Via di Grottarossa 1035-39, 00189 Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Balla
authors.affiliation: Cardiology, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University, Via di Grottarossa 1035-39, 00189 Rome, Italy ; I.R.C.C.S. Neuromed, Pozzilli, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Volpe