A double-blind, placebo-controlled, dose-response study of the effectiveness and safety of lisinopril for children with hypertension.
BACKGROUND
Despite widespread use in hypertensive children, the safety and effectiveness of lisinopril had not been previously tested in a controlled study.


METHODS
This study explored the dose-response relationship and safety of lisinopril in 115 hypertensive children, aged 6 to 16 years. Patients were randomized in a double-blind fashion for 2 weeks to one of three doses by body weight at baseline: <50 kg: low (0.625 mg), middle (2.5 mg), high (20 mg), and > or =50 kg: low (1.25 mg), middle (5 mg), high (40 mg). The dose-response for lisinopril was evaluated by analyzing the change in slope in sitting diastolic and systolic blood pressure (BP) by dose after 2 weeks of therapy compared to baseline. Patients then entered a double-blind withdrawal, where patients were either switched to placebo or continued their current lisinopril treatment for up to 2 weeks. Patients completed period II when their BP returned to baseline. Antihypertensive effectiveness, between placebo and lisinopril was determined for all doses. Adverse events were carefully monitored.


RESULTS
There was a dose-response relationship between the lowest and each of the higher doses of lisinopril. Blood pressure in the placebo group increased after withdrawal of lisinopril. The dose-response relationship was consistent across all subgroups (ie, age, Tanner stage, ethnicity, gender).


CONCLUSIONS
Lisinopril, once daily, is an effective and well-tolerated antihypertensive in children aged 6 to 16 years. An initial dose of 0.07 mg/kg, administered once daily, effectively lowered BP within 2 weeks. Blood pressure was reduced in a dose-dependent fashion.
Soffer
Beth
B
Merck and Co., Inc., West Point, Pennsylvania, USA. beth_soffer@merck.com
Zhang
Zhongxin
Z
Miller
Kenneth
K
Vogt
Beth A
BA
Shahinfar
Shahnaz
S
D000293:Adolescent; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D017706:Lisinopril / Q000008:administration & dosage*; D008297:Male; D010919:Placebos; D011446:Prospective Studies
D000959:Antihypertensive Agents; D010919:Placebos; D017706:Lisinopril