LOSARTAN IN HEART-FAILURE - HEMODYNAMIC-EFFECTS AND TOLERABILITY

Background The aim of the present study was to assess the short- and l ong-term effects of multiple doses of the angiotensin II receptor anta gonist losartan in heart failure. Methods and Results A multicenter, p lacebo-controlled, oral, multidose (2.5, 10, 25, and 50 mg losartan on ce daily) double-blind comparison in patients with symptomatic heart f ailure and impaired left ventricular function (ejection fraction <40%) . Invasive 24-hour hemodynamic assessment was performed after the firs t dose and after 12 weeks of treatment. Clinical status and tolerabili ty of treatment with losartan over the 12 week period were also evalua ted. One hundred fifty-four patients were enrolled, of which 134 met t he protocol criterion of baseline pulmonary capillary wedge pressure g reater than or equal to 13 mm Hg. During short-term administration, sy stemic vascular resistance (SVR) (largest reduction against placebo of 197 dyne.s(-1).cm(-5) at 4 hours) and blood pressure fell significant ly with 50 mg, lesser decreases were seen with 25 mg, pressure (maxima l fall in SVR against placebo, 318 dyne.s(-1).cm(-5) at 5 hours with 5 0 mg). In addition, pulmonary capillary wedge pressure fell with 2.5, 25, and 50 mg (largest reduction against placebo of 6.3 mm Hg at 6 hou rs with 50 mg), cardiac index rose with 25 and 50 mg, and heart rate w as lower with all active treatment groups. Active treatment was well t olerated, and excess cough was not reported. Conclusions This study sh owed that oral losartan administered to patients with symptomatic hear t failure resulted in beneficial hemodynamic effects with short-term a dministration, with additional beneficial hemodynamic effects seen aft er 12 weeks of therapy. Clear effects were seen with both 25 and 50 mg , with the greatest effect seen with 50 mg.