title: Complete inhibition of the renin-angiotensin-aldosterone system; where do we stand?
abstract: OBJECTIVE
  This review presents the role of combination therapy of renin-angiotensin-aldosterone system blockade on cardiovascular and kidney disease.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: aUniversity of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania bVA Maryland Healthcare System and University of Maryland School of Medicine, Baltimore, Maryland cVA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA.
authors.forename: Shan Shan
authors.initials: SS
authors.lastname: Chen
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Seliger
authors.forename: Linda F
authors.initials: LF
authors.lastname: Fried
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D004359:Drug Therapy, Combination; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic; D012084:Renin-Angiotensin System / Q000187:drug effects*; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents