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  Vol. 156 No. 3, 12 FEBRUARY 1996 TABLE OF CONTENTS
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Losartan and Low-Dose Hydrochlorothiazide in Patients With Essential Hypertension

A Double-blind, Placebo-Controlled Trial of Concomitant Administration Compared With Individual Components

James H. MacKay, MD; Karen E. Arcuri, MS; Allan I. Goldberg, MD; Steven M. Snapinn, PhD; Charles S. Sweet, PhD

Arch Intern Med. 1996;156(3):278-285.


Abstract



Background
Angiotensin II acts at the cellular level through specific angiotensin II subtype I, AT-1 receptors. Losartan is the first of a new class of antihypertensive agents that specifically block angiotensin II at AT-1 receptors. By acting on complementary and different pharmacologic mechanisms, the concomitant use of low doses of hydrochlorothiazide with losartan may offer an additive antihypertensive activity with fewer adverse experiences.

Methods
This double-blind study evaluated losartan concomitantly administered with hydrochlorothiazide as initial therapy in 703 patients with essential hypertension.

Results
The greatest reduction in blood pressure was observed in the 50 mg of losartan potassium and 12.5 mg of hydrochlorothiazide group (17.2 mm Hg in sitting systolic blood pressure and 13.2 mm Hg in sitting diastolic blood pressure [P≤.001]), and the effects of the two components appeared to be additive. Seventy-eight percent of the patients treated with 50 mg of losartan potassium and 12.5 mg of hydrochlorothiazide had an excellent or good antihypertensive response (sitting diastolic blood pressure <90 mm Hg or ≥90 mm Hg with a reduction of 10 mm Hg or more). Peak (6 hours after dosing) and trough placebo-adjusted ratios for the losartan-hydrochlorothiazide groups ranged from 62% to 85%, indicating that there was a smooth reduction in sitting diastolic blood pressure that was sustained over 24 hours. The most common clinical adverse experiences (≥4%) that occurred with an incidence slightly greater than that reported by the placebo-treated patients were headache, asthenia or fatigue, dizziness, sinusitis, and upper respiratory infection.

Conclusion
The concomitant administration of losartan potassium, 50 mg, with 12.5 mg of hydrochlorothiazide once daily produced an additive reduction in trough sitting systolic and diastolic blood pressure and was well tolerated.

(Arch Intern Med. 1996;156:278-285)



Author Affiliations



From Heart Research, Providence Medical Center, Portland, Ore (Dr MacKay); and Clinical Cardiovascular Research, Merck Research Laboratories, West Point, Pa (Drs Goldberg, Snapinn, and Sweet and Ms Arcuri).


Footnotes



Dr Sweet is now with New Product Planning, Merck & Co Inc, Whitehouse Station, NJ.



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