Complete inhibition of the renin-angiotensin-aldosterone system; where do we stand?

Curr Opin Nephrol Hypertens. 2014 Sep;23(5):449-55. doi: 10.1097/MNH.0000000000000043.


Purpose of review: This review presents the role of combination therapy of renin-angiotensin-aldosterone system blockade on cardiovascular and kidney disease.

Recent findings: Three large randomized controlled trials comparing combination therapy of renin-angiotensin-aldosterone system blockade to monotherapy in individuals with increased cardiovascular risk, chronic kidney disease, or diabetic nephropathy have been reported. These trials - ONTARGET, ALTITUDE, and VA NEPHRON-D - demonstrated an excess risk of adverse effects [especially acute kidney injury (AKI) and hyperkalemia] with combination therapy, without significant benefit in reducing cardiovascular and renal morbidity.

Summary: Current evidence supports avoiding dual renin-angiotensin-aldosterone system blockade in patients with chronic kidney disease. Subsequent studies of dual renin-angiotensin-aldosterone system blockade should examine adverse event risks and renal progression endpoints.

Publication types

  • Review

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / adverse effects
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Blood Pressure / drug effects*
  • Drug Therapy, Combination
  • Humans
  • Hypertension / complications
  • Hypertension / diagnosis
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Randomized Controlled Trials as Topic
  • Renin-Angiotensin System / drug effects*
  • Risk Assessment
  • Risk Factors
  • Treatment Outcome


  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents