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(Hypertension. 1998;31:684-691.)
© 1998 American Heart Association, Inc.

Scientific Contributions

Efficacy and Tolerability of Losartan in Hypertensive Patients With Renal Impairment

Robert Toto; Pamela Shultz; Leopoldo Raij; Helen Mitchell; Wayne Shaw; Denise Ramjit; Jenny Toh; Shahnaz Shahinfar; ; for the Collaborative Group¹

From the University of Texas Southwestern at Dallas (R.T., H.M.); Veterans Affairs Medical Center, Minneapolis, Minn (P.S., L.R.); and Merck Research Laboratories, West Point, Pa (W.S., D.R., J.T., S.S.).

Correspondence to Robert D. Toto, MD, Director, Clinical Nephrology, Vanderbilt University, School of Medicine, Nashville, TN 37232-2372.

Abstract—We evaluated the blood pressure–lowering activity, tolerability, and safety of losartan in 112 hypertensive (sitting diastolic blood pressure, 90 to 115 mm Hg) patients with chronic renal insufficiency including mild renal insufficiency (30 to 60 mL/min per 1.73 m²; n=51), moderate to severe renal insufficiency (10 to 29 mL/min per 1.73 m²; n=33), or hemodialysis (n=28). After a 3-week placebo period, once-daily losatan was administered for 12 weeks. The daily dose of 50 mg was increased to 100 mg after 4 weeks in patients whose sitting diastolic blood pressure remained 90 mm Hg or was reduced by <5 mm Hg. A second, non–angiotensin-converting enzyme inhibitor, antihypertensive drug was added after 8 weeks as needed. Twenty-four–hour creatinine clearance was determined and renal clearance studies of inulin and para-aminohippurate were done in a subset of 11 patients. Trough sitting blood pressures were reduced at the end of the first week in all groups. At weeks 4, 8, and 12, the reductions in systolic blood pressure/diastolic blood pressure averaged -11.9/-8.7, -10.8/-9.4, and -14.7/-12.1 mm Hg in patients with mild renal insufficiency; -7.7/-6.3, -13.1/-11.8, and -14.1/-10.6 mm Hg, in moderate to severe renal insufficiency; -17.0/-12.7, -19.1/-14.4, and -22.7/-18.0 mm Hg in hemodialysis. Creatinine clearance, glomerular filtration rate, and effective renal plasma flow were stable. Losartan was withdrawn in only 6 patients because of a clinical or laboratory adverse experience. Hyperkalemia (>6 mEq/L) requiring discontinuation of losartan occurred in only one (group 2) patient. We conclude that once-daily losartan, given as monotherapy at doses of 50 or 100 mg or in combination with other antihypertensive drugs, was effective in reducing blood pressure in hypertensive patients with chronic renal disease and that losartan regimens were well tolerated in all groups, including those on hemodialysis.

Key Words: losartan • angiotensin II • renal insufficiency • hemodialysis • renin-angiotensin-aldosterone system

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