PMID- 10193713
OWN - NLM
STAT- MEDLINE
DCOM- 19990419
LR  - 20190708
IS  - 0735-1097 (Print)
IS  - 0735-1097 (Linking)
VI  - 33
IP  - 5
DP  - 1999 Apr
TI  - Dose-related beneficial long-term hemodynamic and clinical efficacy of irbesartan 
      in heart failure.
PG  - 1174-81
AB  - OBJECTIVES: The primary purpose of this study was to determine the acute and 
      long-term hemodynamic and clinical effects of irbesartan in patients with heart 
      failure. BACKGROUND: Inhibition of angiotensin II production by 
      angiotensin-converting enzyme (ACE) inhibitors reduces morbidity and mortality in 
      patients with heart failure. Irbesartan is an orally active antagonist of the 
      angiotensin II AT1 receptor subtype with potential efficacy in heart failure. 
      METHODS: Two hundred eighteen patients with symptomatic heart failure (New York 
      Heart Association [NYHA] class II-IV) and left ventricular ejection fraction < or 
      = 40% participated in the study. Serial hemodynamic measurements were made over 
      24 h following randomization to irbesartan 12.5 mg, 37.5 mg, 75 mg, 150 mg or 
      placebo. After the first dose of study medication, patients receiving placebo 
      were reallocated to one of the four irbesartan doses, treatment was continued for 
      12 weeks and hemodynamic measurements were repeated. RESULTS: Irbesartan induced 
      significant dose-related decreases in pulmonary capillary wedge pressure (average 
      change -5.9+/-0.9 mm Hg and -5.3+/-0.9 mm Hg for irbesartan 75 mg and 150 mg, 
      respectively) after 12 weeks of therapy without causing reflex tachycardia and 
      without increasing plasma norepinephrine. The neurohormonal effects of irbesartan 
      were highly variable and none of the changes was statistically significant. There 
      was a significant dose-related decrease in the percentage of patients 
      discontinuing study medication because of worsening heart failure. Irbesartan was 
      well tolerated without evidence of dose-related cough or azotemia. CONCLUSIONS: 
      Irbesartan, at once-daily doses of 75 mg and 150 mg, induced sustained 
      hemodynamic improvement and prevented worsening heart failure.
FAU - Havranek, E P
AU  - Havranek EP
AD  - Denver Health Medical Center, University of Colorado Health Sciences Center, 
      80204-4507, USA. ehavrane@dhha.org
FAU - Thomas, I
AU  - Thomas I
FAU - Smith, W B
AU  - Smith WB
FAU - Ponce, G A
AU  - Ponce GA
FAU - Bilsker, M
AU  - Bilsker M
FAU - Munger, M A
AU  - Munger MA
FAU - Wolf, R A
AU  - Wolf RA
LA  - eng
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Am Coll Cardiol
JT  - Journal of the American College of Cardiology
JID - 8301365
RN  - 0 (Angiotensin Receptor Antagonists)
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Receptor, Angiotensin, Type 2)
RN  - 0 (Tetrazoles)
RN  - J0E2756Z7N (Irbesartan)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - *Angiotensin Receptor Antagonists
MH  - Antihypertensive Agents/administration & dosage/*therapeutic use
MH  - Biphenyl Compounds/administration & dosage/*therapeutic use
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Female
MH  - Follow-Up Studies
MH  - Heart Failure/blood/*drug therapy/physiopathology
MH  - Hemodynamics/*drug effects
MH  - Humans
MH  - Irbesartan
MH  - Male
MH  - Middle Aged
MH  - Norepinephrine/blood
MH  - Receptor, Angiotensin, Type 1
MH  - Receptor, Angiotensin, Type 2
MH  - Safety
MH  - Single-Blind Method
MH  - Tetrazoles/administration & dosage/*therapeutic use
MH  - Treatment Outcome
EDAT- 1999/04/08 00:00
MHDA- 1999/04/08 00:01
CRDT- 1999/04/08 00:00
PHST- 1999/04/08 00:00 [pubmed]
PHST- 1999/04/08 00:01 [medline]
PHST- 1999/04/08 00:00 [entrez]
AID - S0735109798006950 [pii]
AID - 10.1016/s0735-1097(98)00695-0 [doi]
PST - ppublish
SO  - J Am Coll Cardiol. 1999 Apr;33(5):1174-81. doi: 10.1016/s0735-1097(98)00695-0.