(Hypertension. 1995;25:1345-1350.)
© 1995 American Heart Association, Inc.
Articles |
A Randomized, Placebo-Controlled, Double-Blind, Parallel Study of Various Doses of Losartan Potassium Compared With Enalapril Maleate in Patients With Essential Hypertension
From the Clinical Cardiovascular Research, Merck Research Laboratories, West Point, Pa, and the Western Pennsylvania Hospital, Pittsburgh.
Correspondence to Dr Charles S. Sweet, Clinical Cardiovascular Research, Merck Research Laboratories, West Point, PA 19486.
Abstract The efficacy and safety of various doses of losartan
potassium, a specific and selective angiotensin II receptor antagonist,
were compared with those of placebo and enalapril maleate 20 mg in
patients with mild to moderate essential hypertension in a randomized,
double-blind, parallel study. We randomly allocated 576 patients at the
end of a 4-week placebo baseline period to 8 weeks of once-daily
double-blind treatment with losartan potassium 10, 25, 50, 100, or 150
mg, enalapril maleate 20 mg, or placebo. After 8 weeks of treatment,
mean reductions from baseline in supine systolic/diastolic pressure 24
hours after dosing (trough) for losartan potassium 10, 25, 50, 100, and
150 mg, enalapril maleate 20 mg, and placebo were 7.6/7.9, 7.8/6.8,
13.0/10.1, 8.9/9.9, 10.5/9.7, 14.7/11.2, and 3.8/5.6 mm Hg,
respectively. Compared with mean changes in supine diastolic pressure
in the placebo group, losartan potassium 50 to 150 mg and enalapril
maleate 20 mg produced clinically important and statistically
significant reductions (P
.01) in blood pressure. At 24
hours after dosing, the blood pressure changes obtained with losartan
potassium 50 mg were essentially identical to those obtained with
enalapril maleate 20 mg. While there was a dose-related effect with
losartan potassium from 10 to 50 mg at peak (6 hours after dosing),
doses of 10 and 25 mg were not consistently different from placebo 24
hours after dosing. To assess the once-daily effect of losartan
potassium, trough-to-peak ratios of the mean changes in supine
diastolic pressure after 8 weeks of treatment were calculated. These
placebo-adjusted ratios (losartan potassium 10 mg, 78%; 25 mg, 23%;
50 mg, 60%; 100 mg, 72%; 150 mg, 49%) indicated that losartan
potassium had sustained antihypertensive effects at 24 hours that were
not the result of large peak effects; consequently, once-daily dosing
is appropriate. In terms of safety and tolerability, there were no
dose-related trends for losartan potassium with respect to the
percentage of patients with any adverse experiences, serious adverse
experiences, or drug-related adverse experiences or patients who
withdrew because of an adverse experience. Headache was a common
adverse experience for almost all the treatment groups. Dry cough was
reported as an adverse experience in 8% of the enalapril
maleate–treated patients compared with 3% in both the placebo- and
losartan potassium 50 mg–treated groups.
Key Words: hypertension, essential • angiotensin II • dose-response relationship, drug • angiotensin-converting enzyme inhibitors • losartan • enalapril
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