Combination neurohormonal blockade with ACE inhibitors, angiotensin II antagonists and beta-blockers in patients with congestive heart failure: design of the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) Pilot Study

Can J Cardiol. 1997 Dec;13(12):1166-74.


Background: The Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) Pilot Study is a trial of combination neurohormonal blockade using an angiotensin II antagonist (candesartan), an angiotensin-converting enzyme inhibitor (enalapril) and a beta-blocker (metoprolol) in patients with congestive heart failure (CHF).

Objectives: Primary objectives of stage I are to determine the efficacy (via the 6 min walk test) and safety of candesartan alone, and in combination with enalapril, versus enalapril alone. Secondary objectives are to determine the effect of the above combinations on neurohormones, ventricular function, quality of life and symptoms. Stage II objectives are similar, evaluating the effect of the addition of metoprolol or placebo to the above medication(s).

Design: Randomized, two-stage trial consisting of a three-way comparison (stage I), followed by a 3 x 2 partial factorial design (stage II).

Setting: Sixty out-patient clinics in five countries.

Patients: Patients with symptoms of CHF (New York Heart Association functional classes II to IV), ejection fraction less than 40% and 6 min walk distance of 500 m or less.

Interventions: In stage I, 770 patients are randomized to receive candesartan alone, enalapril alone, or candesartan plus enalapril. After five months (end of stage I), patients are assessed for eligibility to be randomized in stage II. Those who are not candidates for randomization to beta-blocker or placebo are followed on their stage I medications until the end of the study. In stage II, patients are randomized to receive metoprolol or placebo for a further six months in addition to their stage I medications. Endpoints are measured at baseline, end of stage I (week 20) and end of stage II (week 46). STUDY STATUS: The study has recently completed follow-up in both stages. The findings from this study will be used to design a large scale mortality study that will help further define the role of neurohormonal blockade in patients with CHF.

Publication types

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

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use*
  • Angiotensin II / antagonists & inhibitors*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Heart Failure / drug therapy*
  • Humans
  • Pilot Projects
  • Renin-Angiotensin System / drug effects
  • Ventricular Dysfunction, Left / drug therapy*


  • Adrenergic beta-Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Angiotensin II