Ep. Havranek et al., Dose-related beneficial long-term hemodynamic and clinical efficacy of irbesartan in heart failure, J AM COL C, 33(5), 1999, pp. 1174-1181
Citations number
22
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
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-convertin
g enzyme (ACE) inhibitors reduces morbidity and mortality in patients with
heart failure. Irbesartan is an orally active antagonist of the angiotensin
II AT, receptor subtype with potential efficacy in heart failure.
METHODS Two hundred eighteen patients with symptomatic heart failure (New Y
ork Heart Association [NYHA] class II-IV) and left ventricular ejection fra
ction less than or equal to 40% participated in the study. Serial hemodynam
ic measurements were made over 24 h following randomization to irbesartan 1
2.5 mg, 37.5 mg, 75 mg, 150 mg or placebo. After the first dose of study me
dication, patients receiving placebo were reallocated to one of the four ir
besartan doses, treatment was continued for 12 weeks and hemodynamic measur
ements 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 th
erapy without causing reflex tachycardia and without increasing plasma nore
pinephrine. The neurohormonal effects of irbesartan were highly variable an
d none of the changes was statistically significant. There was a significan
t dose-related decrease in the percentage of patients discontinuing study m
edication 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 su
stained hemodynamic improvement and prevented worsening heart failure. (C)
1999 by the American College of Cardiology.