Targeting the renin-angiotensin-aldosterone system in heart failure

Nat Rev Cardiol. 2013 Mar;10(3):125-34. doi: 10.1038/nrcardio.2012.196. Epub 2013 Jan 15.


The renin-angiotensin-aldosterone system is a well-established therapeutic target in the treatment of heart failure (HF). Substantial advances have been made with existing agents--angiotensin-converting enzyme (ACE) inhibitors, angiotensin II-receptor blockers (ARBs), and mineralocorticoid-receptor antagonists (MRAs)--and new data continue to emerge. The indication for the use of MRAs has been broadened to include potentially all patients who have HF with reduced ejection fraction (HFrEF), and ACE inhibitors might have a novel application in patients who are at risk of left ventricular dysfunction (those with aortic valvular disease or pacing-induced heart disease). ARBs have been shown to be a beneficial alternative to ACE inhibitors in HFrEF, but their value when added to ACE inhibitors has been questioned. Upstream, direct renin blockade with aliskiren is being pursued in two large trials of HF, despite the premature halting of a third study. A substantial, unmet need remains in patients who have HF with preserved ejection fraction (HFpEF). New data on spironolactone and LCZ696 (a combined ARB and neprilysin inhibitor) show promise for these patients. Results of the TOPCAT study of spironolactone in patients with HFpEF are awaited, and LCZ696 is now being tested in a large trial in patients with HFrEF.

Publication types

  • Review

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Animals
  • Cardiovascular Agents / adverse effects
  • Cardiovascular Agents / therapeutic use*
  • Heart Failure / drug therapy*
  • Heart Failure / metabolism
  • Heart Failure / physiopathology
  • Humans
  • Mineralocorticoid Receptor Antagonists / therapeutic use
  • Molecular Targeted Therapy*
  • Neprilysin / antagonists & inhibitors
  • Neprilysin / metabolism
  • Renin / antagonists & inhibitors
  • Renin / metabolism
  • Renin-Angiotensin System / drug effects*
  • Treatment Outcome
  • Ventricular Function, Left / drug effects


  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Cardiovascular Agents
  • Mineralocorticoid Receptor Antagonists
  • Renin
  • Neprilysin