Dose-related beneficial long-term hemodynamic and clinical efficacy of irbesartan in heart failure

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.