- R. Willenbrock
- S. Philipp
- V. Mitrovic
- R. Dietz
- Journal of the Renin Angiotensin Aldosterone System
- J Renin Angiotensin Aldosterone Syst 1 (Suppl 1): 24-30
Summary: 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.