title: Comparison of the effects of losartan and enalapril on clinical status and exercise performance in patients with moderate or severe chronic heart failure.
abstract: OBJECTIVE
  This study assessed the feasibility of an efficacy trial comparing angiotensin-converting enzyme inhibition and angiotensin II receptor antagonism in heart failure. Patients with moderate or severe heart failure whose condition had previously been stabilized by treatment with a converting enzyme inhibitor were randomly assigned to receive enalapril or losartan. The study was designed to detect any signs of clinical deterioration during double-blind treatment.
  
  
  BACKGROUND
  Losartan is a specific, nonpeptide angiotensin II receptor-1 antagonist with a vasodilator hemodynamic profile similar to that of converting enzyme inhibitors. Although therapy with specific receptor blockade has certain theoretic advantages over nonspecific converting enzyme inhibition, demonstration of a comparable therapeutic effect in patients with congestive heart failure will require a major effort comparing two active agents.
  
  
  METHODS
  One hundred sixty-six patients with stable heart failure in New York Heart Association functional class III or IV and an ejection fraction < or = 35% were included in a multicenter, double-blind, parallel, enalapril-controlled trial. After a 3-week stabilization period with optimal therapy, including digitalis, diuretic drugs and a converting enzyme inhibitor, patients were randomly assigned to 8 weeks of therapy with losartan, 25 mg/day (n = 52); losartan, 50 mg/day (n = 56); or enalapril, 20 mg/day (n = 58). Patients were assessed with frequent clinical and laboratory evaluation and exercise testing.
  
  
  RESULTS
  No significant differences between groups in terms of changes in exercise capacity (6-min walk test), clinical status (dyspnea-fatigue index), neurohumoral activation (norepinephrine, N-terminal atrial natriuretic factor), laboratory evaluation or incidence of adverse experience were observed.
  
  
  CONCLUSIONS
  The results suggest that losartan and enalapril are of comparable efficacy and tolerability in the short-term treatment of moderate or severe congestive heart failure. A trial designed to compare the efficacy, tolerability and effect on mortality of long-term angiotensin II receptor blockade with converting enzyme inhibition is both feasible and ethically responsible.
authors.affiliation: Hjertelaget Research Foundation, Stavanger, Norway.
authors.forename: K
authors.initials: K
authors.lastname: Dickstein
authors.forename: P
authors.initials: P
authors.lastname: Chang
authors.forename: R
authors.initials: R
authors.lastname: Willenheimer
authors.forename: S
authors.initials: S
authors.lastname: Haunsø
authors.forename: J
authors.initials: J
authors.lastname: Remes
authors.forename: C
authors.initials: C
authors.lastname: Hall
authors.forename: J
authors.initials: J
authors.lastname: Kjekshus
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D002908:Chronic Disease; D015986:Confounding Factors, Epidemiologic; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000494:pharmacology / Q000627:therapeutic use*; D005080:Exercise Test / Q000187:drug effects*; D005240:Feasibility Studies; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D019808:Losartan; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D004656:Enalapril; D019808:Losartan