title: Comparative effects of losartan and enalapril on exercise capacity and clinical status in patients with heart failure. The Losartan Pilot Exercise Study Investigators.
abstract: OBJECTIVE
  This study was designed to determine 1) whether 12-week oral administration of losartan, an angiotensin II receptor antagonist, in patients with heart failure is well tolerated; and 2) whether functional capacity and clinical status of patients with heart failure in whom treatment with an angiotensin-converting enzyme (ACE) inhibitor is replaced with losartan for 12 weeks will remain similar to that noted in patients in whom treatment with an ACE inhibitor is continued.
  
  
  BACKGROUND
  Losartan is a specific, nonpeptide angiotensin II receptor antagonist. Although specific receptor blockade with losartan has certain theoretic advantages over nonspecific ACE inhibition, definitive demonstration of comparable effects in patients with congestive heart failure is lacking.
  
  
  METHODS
  A double-blind, multicenter, randomized, parallel, enalapril-controlled study was conducted in 116 patients with congestive heart failure (New York Heart Association functional classes II to IV) and left ventricular ejection fraction < or = 45% previously treated with stable doses of ACE inhibitors and diuretic agents, with or without concurrent digitalis and other vasodilators. After a baseline exercise period, open-label ACE inhibitors were discontinued, and patients were randomly assigned to 12 weeks of therapy with losartan, 25 mg/day (n = 38); losartan, 50 mg/day (n = 40); or enalapril, 20 mg/day (n = 38). Drug efficacy was evaluated by changes in maximal treadmill exercise time (using a modified Naughton protocol), 6-min walk test, left ventricular ejection fraction and dyspnea-fatigue index. Safety was measured by the incidence of clinical and laboratory adverse experiences.
  
  
  RESULTS
  The treadmill exercise time and the 6-min walk test did not change significantly after replacement of ACE inhibitor therapy with losartan. Similarly, a significant change was not observed in either the dyspnea-fatigue index or left ventricular ejection fraction at the end of double-blind period relative to baseline.
  
  
  CONCLUSIONS
  Losartan was generally well tolerated and comparable to enalapril in terms of exercise tolerance in this short-term (12-week) study of patients with heart failure. The clinical effects of long-term angiotensin II receptor blockade compared with ACE inhibition remain to be studied.
authors.affiliation: University of Chicago Medical Center, Illinois 60637, USA. rlang@medicine.bsd.uchicago
authors.forename: R M
authors.initials: RM
authors.lastname: Lang
authors.forename: U
authors.initials: U
authors.lastname: Elkayam
authors.forename: L G
authors.initials: LG
authors.lastname: Yellen
authors.forename: D
authors.initials: D
authors.lastname: Krauss
authors.forename: R S
authors.initials: RS
authors.lastname: McKelvie
authors.forename: D E
authors.initials: DE
authors.lastname: Vaughan
authors.forename: D E
authors.initials: DE
authors.lastname: Ney
authors.forename: L
authors.initials: L
authors.lastname: Makris
authors.forename: P I
authors.initials: PI
authors.lastname: Chang
mesh_terms: D000203:Activities of Daily Living; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D004656:Enalapril / Q000627:therapeutic use*; D005080:Exercise Test / Q000187:drug effects; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D013318:Stroke Volume / Q000187:drug effects
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D019808:Losartan