The purpose of this multicenter trial was to compare the antihypertens
ive efficacy and safety of losartan potassium (losartan), a selective
angiotensin II receptor antagonist, when added to hydrochlorothiazide
in hypertensive patients whose blood pressure was not adequately contr
olled by 25 mg hydrochlorothiazide monotherapy. After a 4-week monothe
rapy period of 25 mg hydrochlorothiazide, 304 patients with trough (22
to 26 hours postdose) sitting diastolic pressure between 93 and 120 m
m Hg were maintained on 25 mg hydrochlorothiazide and randomized doubl
e-blind into treatment arms consisting of either 25, 50, or 100 mg los
artan or placebo once daily for 12 weeks. The reductions in sitting di
astolic pressure for patients treated with 25, 50, or 100 mg losartan
concomitantly administered with 25 mg hydrochlorothiazide were signifi
cantly greater (P less than or equal to.05) than the reductions observ
ed in the 25 mg hydrochlorothiazide plus placebo group beginning 1 wee
k after randomization. The antihypertensive response in all groups was
greater at week 3 than week 1, with some additional decrease in blood
pressure in some groups at later times. Sitting systolic pressures we
re also significantly reduced in each group over time. Standing blood
pressures at week 12 were similar to sitting blood pressures. A dose-r
esponse relationship to losartan was observed in this patient populati
on. The percentages of the total drug-related clinical adverse experie
nces as assessed by the investigator were generally similar in the 25,
50, and 100 mg losartan plus 25 mg hydrochlorothiazide groups (10.3%,
24.4%, and 20.0%, respectively) compared with the placebo plus 25 mg
hydrochlorothiazide group (24.7%). In addition, the anticipated hydroc
hlorothiazide-associated decrease in serum potassium and the increase
in serum uric acid appeared to be somewhat blunted in the losartan plu
s hydrochlorothiazide groups relative to the hydrochlorothiazide plus
placebo group. These results demonstrate that the addition of 25, 50,
and 100 mg losartan to 25 mg hydrochlorothiazide produced a significan
t and dose-related reduction in blood pressure at trough after 12 week
s compared with the 25 mg hydrochlorothiazide plus placebo group. In a
ddition, losartan given concomitantly with hydrochlorothiazide was gen
erally well tolerated in this study.