Sudden death prevention in heart failure: The case of CIBIS III

Abstract

CIBIS III completes a fundamental scientific phase of a sequence of large clinical trials (1-7) which has established the current therapeutic principles for the management of chronic heart failure (CHF) patients (8). These comprise the use of ACE inhibitors and beta-blockers. However, while ACE inhibitors, by antagonizing the synthesis of angiotensin II, found their natural pathway from hypertension into CHF, betablockers followed a controversial trail. They appeared effective in the BEHAT (9) trial after myocardial infarction (MI) even in patients with depressed left ventricular (LV) function. Nonetheless, the general view of CHF as an almost exclusively cardio-circulatory mechanical disease/remodelling led to the use of inotropic interventions, with non-infrequent negative consequences on mortality (10). Furthermore, this view prevented the conception of using antiadrenergic interventions in CHF which consequently remained a strong contraindication to the use of beta-blockers for many years. Beginning with CIBIS II, a number of trials have proven that beta-blocker therapy improves survival in CHF, with a specific action on arrhythmic sudden cardiac death (SCD) in patients with optimum background therapy, including the use of ACE inhibitors. This did not happen by chance, as a strong experimental ground had already existed and has further grown during the last few years (11); very soon after its first manifestation, ischemic heart disease triggers a profound remodelling of the autonomic nervous system, resulting in receptor changes and sprouting of neural fibers (12, 13). In line with this background stands the huge amount of clinical evidence documenting the antifibrillatory action of anti-adrenergic interventions. In contrast to the rapid activation of the autonomic nervous system, the renin-angiotensin system (RAS) acts primarily by promoting the progressive myocardial architectural changes, leading to inefficient LV function and pump failure (14). The same process indirectly contributes to the genesis of an arrhythmogenic substrate for SCD to occur (15, 16). However, despite the bulk of evidence documenting the striking efficacy of ACE inhibitors and, more so, of betablockers in CHF, both drugs are underused. Recent surveys indicate that ACE inhibitors are given to only 60% of eligible patients (17) (Fig. 1) and the picture for beta-blockers is even worse, as the percentage of treated patients among those eligible is as low as around 30%. Additionally, beta-blocker therapy is mostly given to low risk patients and as late as 6 months after a first hospitalisation for HF (18). The immediate consequence of the mistrust in (or fear of) using adequate pharmacological therapy according to the international guidelines has been the boosted use of implantable cardioverter defibrillators (ICD) in any patient with depressed LV systolic function. Heart International / Vol. 2 no. 2, 2006 / pp. 73-77 © Wichtig Editore, 2006

DOI: 10.4081/hi.2006.73

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Cite this paper

@inproceedings{Vanoli2006SuddenDP, title={Sudden death prevention in heart failure: The case of CIBIS III}, author={Emilio Vanoli and Livio Dei Cas and Ronnie B Willenheimer}, booktitle={Heart international}, year={2006} }