Randomized trial of candesartan cilexetil in the treatment of patients with congestive heart failure and a history of intolerance to angiotensin-converting enzyme inhibitors

Am Heart J. 2000 Apr;139(4):609-17. doi: 10.1016/s0002-8703(00)90037-1.


Background: Many patients with congestive heart failure do not receive the benefits of angiotensin-converting enzyme (ACE) inhibitors because of intolerance. We sought to determine the tolerability of an angiotensin II receptor blocker, candesartan cilexetil, among patients considered intolerant of ACE inhibitors.

Methods: Patients with CHF, left ventricular ejection fraction less than 35%, and history of discontinuing an ACE inhibitor because of intolerance underwent double-blind randomization in a 2:1 ratio to receive candesartan (n = 179) or a placebo (n = 91). The initial dosage of candesartan was 4 mg/d; the dosage was increased to 16 mg/d if the drug was tolerated. A history of intolerance of ACE inhibitor was attributed to cough (67% of patients), hypotension (15%), or renal dysfunction (11%).

Results: The study drug was continued for 12 weeks by 82.7% of patients who received candesartan versus 86.8% of patients who received the placebo. This 4.1% greater discontinuation rate with active therapy was not significant; the 95% confidence interval ranged from 4.8% more discontinuation with placebo to 13% more with candesartan. Titration to the 16-mg target dose was possible for 69% of patients who received candesartan versus 84% of those who received the placebo. Frequencies of death and morbidity were not significantly different between the candesartan and placebo groups (death 3.4% and 3.3%, worsening heart failure 8.4% and 13.2%, myocardial infarction 2.8% and 5.5%, all-cause hospitalization 12.8% and 18.7%, and death or hospitalization for heart failure 11.7% and 14.3%).

Conclusions: Candesartan was well tolerated by this population. The effect of candesartan on major clinical end points, including death, remains to be determined.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Benzimidazoles / adverse effects
  • Benzimidazoles / therapeutic use*
  • Biphenyl Compounds / adverse effects
  • Biphenyl Compounds / therapeutic use*
  • Cause of Death
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Heart Failure / diagnosis
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Hemodynamics / drug effects
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects
  • Survival Rate
  • Tetrazoles*
  • Ventricular Dysfunction, Left / diagnosis
  • Ventricular Dysfunction, Left / drug therapy
  • Ventricular Function, Left / drug effects


  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Benzimidazoles
  • Biphenyl Compounds
  • Tetrazoles
  • candesartan cilexetil