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This study was aimed at evaluating the antihypertensive effect of lisinopril and hydrochlorothiazide administered in the fixed combination of 20 and 12.5 mg, respectively, on clinic and 24-h blood pressure in elderly patients (age, 68.8 ± 5.8 years, mean ± SD) with mild-to-moderate essential systodiastolic or isolated systolic hypertension. After a washout period of 4 weeks, patients received once daily lisinopril combined with hydrochlorothiazide for a 6-week period. At the end of the washout and treatment periods, clinic blood pressure was assessed 24 h after dosing, and 24-h ambulatory blood pressure was monitored, taking blood pressure readings every 15 min. Pretreatment clinic blood pressure was 171.3 ± 14.0/103.7 ± 5.1 mm Hg (systolic/diastolic) in the group with systodiastolic hypertension (n = 405) and 179.6 ± 9.4/83.6 ± 5.4 mm Hg in the group with isolated systolic hypertension (n = 165). The corresponding 24-h average blood pressures were 144.1 ± 13.9/88.7 ± 8.4 mm Hg (n = 114) and 150.7 ± 15.5/80.8 ± 9.4 mm Hg (n = 40). Clinic blood pressure was significantly reduced by treatment in both groups. This was the case also for ambulatory blood pressure, which was reduced by 9.6 ± 0.9%/9.9 ± 0.9% in systodiastolic and by 11.8 ± 1.3%/8.5 ± 1.5% in isolated patients with systolic hypertension (p < 0.05 at least for all differences). The antihypertensive effect was similar in patients older and younger than 70 years. In all groups, it was manifest both during the day and the nighttime and was still significant after 24 h. Thus single daily administration of combined lisinopril-hydrochlorothiazide effectively reduces blood pressure in elderly patients with hypertension.