Rationale, background, and design of the randomized angiotensin receptor antagonist--angiotensin-converting enzyme inhibitor study (RAAS).
The randomized angiotensin receptor antagonist--angiotensin converting enzyme (ACE)--Inhibitor Study (RAAS) was designed to test the hypothesis that the addition of an angiotensin II type 1 receptor blocking agent, losartan 50 mg/day, to an ACE-inhibitor, enalapril 10 mg twice a day (group 1), will be more effective than standard-dose enalapril 10 mg twice a day (group 2) or high-dose enalapril alone 20 mg twice a day (group 3), in blocking the activation of the renin angiotensin aldosterone system in patients with heart failure and left ventricular systolic dysfunction. The addition of an angiotensin II type 1 receptor blocking agent to an ACE inhibitor would theoretically block ACE as well as non-ACE-dependent angiotensin II formation while maintaining the potential beneficial effect of ACE inhibitor-induced bradykinin formation. One hundred twenty patients with left ventricular systolic dysfunction and moderate to severe heart failure despite treatment with an ACE inhibitor will be randomized to 1 of the 3 groups and followed for 6 weeks, with an optional long-term week extension to determine the safety and tolerability of the combination of losaratan and enalapril, its effectiveness in preventing rest and exercise-induced neurohumoral activation (plasma norepinephrine, N-terminal proatrial natriuretic factor, angiotensin II, and aldosterone), as well as quality of life and exercise performance (6-minute walk test).
Pitt
B
B
University of Michigan School of Medicine, Ann Arbor, USA.
Chang
P
P
Grossman
W
W
Dunlay
M
M
Timmermans
P B
PB
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000008:administration & dosage*; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D019808:Losartan; D010865:Pilot Projects; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D013777:Tetrazoles / Q000008:administration & dosage*; D017186:Titrimetry; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy*
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D004656:Enalapril; D019808:Losartan