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(Hypertension. 1995;26:112-117.)
© 1995 American Heart Association, Inc.

Articles

Effects of Losartan on a Background of Hydrochlorothiazide in Patients With Hypertension

Beth A. Soffer; Jackson T. Wright, Jr; J. Howard Pratt; Brian Wiens; Allan I. Goldberg; Charles S. Sweet

From Merck Research Laboratories, Clinical Cardiovascular Research, West Point, Pa; Case Western Reserve University, Cleveland, Ohio; and Indiana University, Indianapolis.

Correspondence to Dr C.S. Sweet, Merck Research Laboratories, Clinical Cardiovascular Research, West Point, PA 19486.

Abstract The purpose of this multicenter trial was to compare the antihypertensive 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 controlled by 25 mg hydrochlorothiazide monotherapy. After a 4-week monotherapy period of 25 mg hydrochlorothiazide, 304 patients with trough (22 to 26 hours postdose) sitting diastolic pressure between 93 and 120 mm Hg were maintained on 25 mg hydrochlorothiazide and randomized double-blind into treatment arms consisting of either 25, 50, or 100 mg losartan or placebo once daily for 12 weeks. The reductions in sitting diastolic pressure for patients treated with 25, 50, or 100 mg losartan concomitantly administered with 25 mg hydrochlorothiazide were significantly greater (P.05) than the reductions observed in the 25 mg hydrochlorothiazide plus placebo group beginning 1 week 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 were also significantly reduced in each group over time. Standing blood pressures at week 12 were similar to sitting blood pressures. A dose-response relationship to losartan was observed in this patient population. The percentages of the total drug-related clinical adverse experiences 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 hydrochlorothiazide-associated decrease in serum potassium and the increase in serum uric acid appeared to be somewhat blunted in the losartan plus 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 significant and dose-related reduction in blood pressure at trough after 12 weeks compared with the 25 mg hydrochlorothiazide plus placebo group. In addition, losartan given concomitantly with hydrochlorothiazide was generally well tolerated in this study.

Key Words: hydrochlorothiazide • losartan potassium • hypertension, essential • receptors, angiotensin • clinical trials

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