Clinical consequences of angiotensin-converting enzyme inhibitor withdrawal in chronic heart failure: a double-blind, placebo-controlled study of quinapril. The Quinapril Heart Failure Trial Investigators

J Am Coll Cardiol. 1993 Nov 15;22(6):1557-63. doi: 10.1016/0735-1097(93)90578-o.


Objectives: This study was performed to assess the efficacy, safety and clinical consequences of abrupt cessation of quinapril therapy in a placebo-controlled, randomized, double-blind withdrawal trial.

Background: Angiotensin-converting enzyme inhibitor therapy has assumed a pivotal role in the treatment of chronic heart failure. Quinapril hydrochloride, a nonsulfydryl angiotensin-converting enzyme inhibitor, has shown beneficial clinical effects in previous studies.

Methods: After > or = 10 weeks of single-blind quinapril therapy, 224 patients with New York Heart Association class II or III heart failure were randomized in double-blind fashion to continue quinapril (n = 114) or to receive placebo (n = 110) for 16 weeks. Changes in treadmill exercise time, New York Heart Association functional class, quality of life and symptoms of heart failure were assessed.

Results: Patients withdrawn to placebo had a significant deterioration in exercise tolerance (median change -16 s with placebo vs. +3 s with quinapril, p = 0.015). New York Heart Association functional class (p = 0.004) and quality of life were improved and signs and symptoms of congestive heart failure were lessened in those remaining on quinapril therapy compared with those receiving placebo. During double-blind treatment, 18 patients were withdrawn from the placebo group because of worsening heart failure compared with 5 patients withdrawn from quinapril treatment (p < 0.001). Rather than a precipitous deterioration of clinical status or early incidence of adverse events, withdrawal from quinapril was associated with steady worsening of heart failure, beginning 4 to 6 weeks after randomization to placebo.

Conclusions: Quinapril is effective and safe for maintaining clinical stability in patients with moderate congestive heart failure. Withdrawal of quinapril from patients with heart failure results in a slow progressive decline in clinical status.

Publication types

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

MeSH terms

  • Aged
  • Analysis of Variance
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Chronic Disease
  • Double-Blind Method
  • Exercise / physiology
  • Female
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology
  • Humans
  • Isoquinolines / adverse effects
  • Isoquinolines / therapeutic use*
  • Linear Models
  • Male
  • Middle Aged
  • Quinapril
  • Substance Withdrawal Syndrome / physiopathology*
  • Tetrahydroisoquinolines*


  • Angiotensin-Converting Enzyme Inhibitors
  • Isoquinolines
  • Tetrahydroisoquinolines
  • Quinapril