(Circulation. 1995;91:691-697.)
© 1995 American Heart Association, Inc.
Articles |
Losartan in Heart Failure
Hemodynamic Effects and Tolerability
From the Christchurch Hospital (I.C., H.I.), Christchurch, New Zealand; Minerva Consertal (N.A.), Sacramento, Calif; Hammersmith Hospital (J.C., N.S.), London, UK; Central Hospital in Rogaland (K.D.), Stavanger, Norway; Sarasota Heart Institute (M.F.), Sarasota, Fla; Baylor College of Medicine (J.Y.), Houston, Tex; and Merck Research Laboratories (G.K., L.M., E.R.), West Point, Pa.
Correspondence to Dr Ian Crozier, Department of Cardiology, Christchurch Hospital, Riccarton Ave, Private Bag, Christchurch, New Zealand.
Background The aim of the present study was to assess the short- and long-term effects of multiple doses of the angiotensin II receptor antagonist losartan in heart failure.
Methods and Results A multicenter, placebo-controlled,
oral, multidose (2.5, 10, 25, and 50 mg losartan once daily)
double-blind comparison in patients with symptomatic heart failure and
impaired left ventricular function (ejection fraction <40%). Invasive
24-hour hemodynamic assessment was performed after the first dose and
after 12 weeks of treatment. Clinical status and tolerability of
treatment with losartan over the 12-week period were also evaluated.
One hundred fifty-four patients were enrolled, of which 134 met the
protocol criterion of baseline pulmonary capillary wedge pressure 
13
mm Hg. During short-term administration, systemic vascular resistance
(SVR) (largest reduction against placebo of 197
dyne · s-1 · cm-5 at 4 hours)
and
blood pressure fell significantly with 50 mg, lesser decreases were
seen with 25 mg, and no discernible effects were seen with 2.5 and 10
mg. After 12 weeks of treatment, similar effects were seen on SVR and
blood pressure (maximal fall in SVR against placebo, 318
dyne · s-1 · cm-5 at 5 hours
with 50
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 hours
with 50 mg), cardiac index rose with 25 and 50 mg, and heart rate was
lower with all active treatment groups. Active treatment was well
tolerated, and excess cough was not reported.
Conclusions This study showed that oral losartan administered to patients with symptomatic heart failure resulted in beneficial hemodynamic effects with short-term administration, with additional beneficial hemodynamic effects seen after 12 weeks of therapy. Clear effects were seen with both 25 and 50 mg, with the greatest effect seen with 50 mg.
Key Words: losartan • heart failure • angiotensin
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