Two dose-response studies utilizing a once-daily regimen were conducted in 438 mild to moderate hypertensive patients not on a diuretic. Blood pressure was measured 24 hours after dosing. An antihypertensive effect of Zestril was seen with 5 mg of Zestril in some patients. However, in both studies blood pressure reduction occurred sooner and was greater in patients treated with 10 mg, 20 mg or 80 mg of Zestril than patients treated with 5 mg of Zestril.

In controlled clinical studies of patients with mild to moderate hypertension, patients were treated with Zestril 20 mg to 80 mg daily, hydrochlorothiazide 12.5 mg to 50 mg daily or atenolol 50 mg to 200 mg daily; and in other studies of patients with moderate to severe hypertension, patients were treated with Zestril 20 mg to 80 mg daily or metoprolol 100 mg to 200 mg daily. Zestril demonstrated superior reductions of systolic and diastolic compared to hydrochlorothiazide in a population that was 75% Caucasian. Zestril was approximately equivalent to atenolol and metoprolol in reducing diastolic blood pressure, and had somewhat greater effects on systolic blood pressure.

Zestril had similar blood pressure reductions and adverse effects in younger and older (> 65 years) patients. It was less effective in reducing blood pressure in Blacks than in Caucasians.

In hemodynamic studies of Zestril in patients with essential hypertension, blood pressure reduction was accompanied by a reduction in peripheral arterial resistance with little or no change in cardiac output and in heart rate. In a study in nine hypertensive patients, following administration of Zestril, there was an increase in mean renal blood flow that was not significant. Data from several small studies are inconsistent with respect to the effect of lisinopril on glomerular filtration rate in hypertensive patients with normal renal function, but suggest that changes, if any, are not large.

In patients with renovascular hypertension Zestril has been shown to be well tolerated and effective in reducing blood pressure [see  Warnings and Precautions (5.3) ].

Pediatric Patients: In a clinical study involving 115 hypertensive pediatric patients 6 to 16 years of age, patients who weighed < 50 kg received either 0.625 mg, 2.5 mg or 20 mg of Zestril once daily and patients who weighed ≥ 50 kg received either 1.25 mg, 5 mg, or 40 mg of Zestril once daily. At the end of 2 weeks, Zestril lowered trough blood pressure in a dose-dependent manner with antihypertensive efficacy demonstrated at doses > 1.25 mg (0.02 mg per kg). This effect was confirmed in a randomized withdrawal phase, where the diastolic pressure rose by about 9 mmHg more in patients randomized to placebo than compared to patients who remained on the middle and high doses of lisinopril. The dose-dependent antihypertensive effect of Zestril was consistent across several demographic subgroups: age, Tanner stage, gender, and race. In this study, lisinopril was generally well-tolerated.

In the above pediatric studies, Zestril was given either as tablets or in a suspension for those children and infants who were unable to swallow tablets or who required a lower dose than is available in tablet form [see  Dosage and Administration (2.1) ].