Combining neuroendocrine inhibitors in heart failure: reflections on safety and efficacy

Am J Med. 2007 Dec;120(12):1090.e1-8. doi: 10.1016/j.amjmed.2007.02.029.


Neuroendocrine activation in heart failure has become the major target of pharmacotherapy for this growing epidemic. Agents targeting the renin-angiotensin-aldosterone and sympathetic nervous systems have shown cardiovascular and survival benefits in clinical trials. Beta-blockers and angiotensin-converting enzyme (ACE) inhibitors remain the mainstream initial therapy. The benefits of aldosterone antagonists have been demonstrated in advanced heart failure (spironolactone) and after myocardial infarction complicated by left ventricular dysfunction and heart failure (eplerenone). Emerging clinical evidence demonstrated that angiotensin receptor blockers may be a reasonable alternative to ACE inhibitors in patients with heart failure (candesartan) and following myocardial infarction complicated by heart failure or left ventricular dysfunction (valsartan). Angiotensin receptor blockers (candesartan) also provided incremental benefits when added to ACE inhibitors in chronic heart failure. Thus, combining neuroendocrine inhibitors in heart failure appears both biologically plausible and evidence-based. However, this approach raised concerns about side effects, such as hypotension, renal insufficiency, hyperkalemia, and others. Close follow-up and implementation of evidence-based medicine (ie, using agents and doses proven beneficial in clinical trials) should therefore be undertaken when combining neuroendocrine inhibitors.

Publication types

  • Review

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage
  • Adrenergic beta-Antagonists / adverse effects
  • Adrenergic beta-Antagonists / therapeutic use*
  • Angiotensin II Type 1 Receptor Blockers / administration & dosage
  • Angiotensin II Type 1 Receptor Blockers / adverse effects
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Drug Therapy, Combination
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Humans
  • Hyperkalemia / chemically induced
  • Hypotension / chemically induced
  • Renal Insufficiency / chemically induced


  • Adrenergic beta-Antagonists
  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors