EFFICACY AND TOLERABILITY OF LOSARTAN IN HYPERTENSIVE PATIENTS WITH RENAL IMPAIRMENT

We evaluated the blood pressure-lowering activity, tolerability, and s afety losartan in 112 hypertensive (sitting diastolic blood pressure, 90 to 115 mm Hg) patients with chronic renal insufficiency including m ild renal insufficiency (30 to 60 mL/min per 1.73 m(2); n=51), moderat e to severe renal insufficiency (10 to 29 mL/min per 1.73 m(2); n=33), or hemodialysis (n=28). After a 3-week placebo period, once-daily los atan was administered for I:! weeks. The daily dose of 50 mg was incre ased to 100 mg after 4 weeks in patients whose sitting diastolic blood pressure remained greater than or equal to 90 mm Hg or was reduced by <5 mm Hg. A second, non-angiotensin-converting enzyme inhibitor, anti hypertensive drug was added after 8 weeks as needed. Twenty-four-hour creatinine clearance was determined and renal clearance studies of inu lin and para-aminohippurate were done in a subset oi 11 patients. Trou gh sitting blood pressures were reduced at the end of the first week i n ail groups, At weeks Jr, 8, and 12, the reductions in systolic blood pressure/diastolic blood pressure averaged -11.9/-8.7, -10.8/-9.4, an d -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 in sufficiency: -17.0/-12.7, -19.1/-14.4, and -27.7/-18.0 mm Hg in hemodi alysis. Creatinine clearance, glomerular filtration rate, and effectiv e renal plasma now were stable, Losartan was withdrawn in only 6 patie nts because of a clinical or laboratory adverse experience. Hyperkalem ia (>6 mEq/L) requiring discontinuation of losartan occurred in only o ne (group 2) patient. We conclude that once-daily losartan, given as m onotherapy at doses of 50 or 100 mg or in combination with other antih ypertensive drugs, was effective in reducing blood pressure in hyperte nsive patients with chronic renal disease and that losartan regimens w ere well tolerated in all groups, including those on hemodialysis.