Comparison of the effects of losartan and enalapril on clinical status and exercise performance in patients with moderate or severe chronic heart failure.
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.
Dickstein
K
K
Hjertelaget Research Foundation, Stavanger, Norway.
Chang
P
P
Willenheimer
R
R
Haunsø
S
S
Remes
J
J
Hall
C
C
Kjekshus
J
J
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
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D004656:Enalapril; D019808:Losartan