title: Angiotensin receptor blocker therapy for heart failure patients: is combination treatment a feasible prospect?
abstract: BACKGROUND
  The addition of the angiotensin II type 1 receptor blocker (ARB) candesartan to a angiotensin-converting enzyme inhibitor (ACEI) has been associated with improved clinical outcomes in patients with heart failure. However many do not tolerate combination therapy and concerns have been raised regarding excessive neurohormonal inhibition.
  
  
  OBJECTIVE
  The majority of patients with chronic heart failure are not eligible or do not tolerate combination therapy with an ACEEI and ARB.
  
  
  METHODS
  We prospectively evaluated 115 consecutive patients with heart failure (median age 74 y; 74% males; mean left ventricular ejection fraction 30%) within a district general hospital for eligibility and tolerance to combination therapy using candesartan in addition to recommended doses of an ACEI.
  
  
  RESULTS
  Overall, 109 (95%) were ineligible to initiate candesartan. The most frequent reasons were that, despite best efforts at optimization, 77% of patients were unable to achieve recommended doses of an ACEI, 29% were relatively asymptomatic, 20% had symptomatic hypotension, and 35% were already taking an ARB due to previous ACEI "intolerance." Overall, 6 (5%) of patients satisfied the eligibility criteria of whom 3 (3% of total) were already taking "optimal" doses of an ARB in addition to an ACEI. The remaining 3 patients commenced the titration schedule with candesartan. All 3 patients failed the first titration phase (4 mg once daily) within 2 weeks of initiation, due to the development of hyperkalemia.
  
  
  CONCLUSIONS
  The use of combination therapy with an ARB in addition to recommended doses of ACEI does not appear feasible in patients with heart failure in the general population, as the vast majority are not eligible.
authors.affiliation: Clinical Cardiology, National Heart and Lung Institute, Imperial College, London, United Kingdom. p.mehta@imperial.ac.uk
authors.forename: P A
authors.initials: PA
authors.lastname: Mehta
authors.forename: S
authors.initials: S
authors.lastname: McDonagh
authors.forename: J
authors.initials: J
authors.lastname: Phillips
authors.forename: R
authors.initials: R
authors.lastname: Grocott-Mason
authors.forename: S W
authors.initials: SW
authors.lastname: Dubrey
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D004359:Drug Therapy, Combination; D005240:Feasibility Studies; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006767:Hospitals, District; D006769:Hospitals, General; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced; D008131:London; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D017410:Practice Guidelines as Topic; D011446:Prospective Studies; D013318:Stroke Volume / Q000187:drug effects; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C081643:candesartan