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Neurohumoral blockade in CHF management

Franz-Volhard-Klinik, Charité, Humboldt-University of Berlin, Berlin, Germany, willenbrock{at}fvk-berlin.de

Sebastian Philipp

Franz-Volhard-Klinik, Charité, Humboldt-University of Berlin, Berlin, Germany

Veslin Mitrovic

Max-Planck-Institute and Kerckhoff-Klinik, Bad Nauheim, Germany

Rainer Dietz

Franz-Volhard-Klinik, Charité, Humboldt-University of Berlin, Berlin, Germany

Is heart failure an endocrine disease? Historically, congestive heart failure (CHF) has often been regarded as a mechanical and haemodynamic condition. However, there is now strong evidence that the activation of neuroendocrine systems, like the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system, as well as the activation of natriuretic peptides, endothelin and vasopressin, play key roles in the progression of CHF. In this context, agents targeting neurohormones offer a highly rational approach to CHF management, with ACE inhibitors, aldosterone antagonists and beta-adrenergic blockade improving the prognosis for many patients. Although relevant improvements in clinical status and survival can be achieved with these drug classes, mortality rates for patients with CHF are still very high. Moreover, most patients do not receive these proven life-prolonging drugs, partially due to fear of adverse events, such as hypotension (with ACE inhibitors), gynaecomastia (with spironolactone) and fatigue (with beta-blockers).

New agents that combine efficacy with better tolerability are therefore needed. The angiotensin II type 1 (AT₁)-receptor blockers have the potential to fulfil both these requirements, by blocking the deleterious cardiovascular and haemodynamic effects of angiotensin II while offering placebo-like tolerability. As shown with candesartan, AT₁-receptor blockers also modulate the levels of other neurohormones, including aldosterone and atrial natriuretic peptide (ANP). Combined with its tight, long-lasting binding to AT₁-receptors, this characteristic gives candesartan the potential for complete blockade of the RAAS-neurohormonal axis, along with the great potential to improve clinical outcomes.

Key Words: congestive heart failure • renin-angiotensin-aldosterone system • neurohormones • angiotensin II receptor

Journal of Renin-Angiotensin-Aldosterone System, Vol. 1, No. 1 suppl, 24-30 (2000)
DOI: 10.3317/jraas.2000.030


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