Beta-blocker/thiazide combination for treatment of hypertensive children: a randomized double-blind, placebo-controlled trial.
Antihypertensive medications are used extensively in children despite a paucity of randomized, placebo-controlled trials. This study was among the first randomized, controlled pediatric antihypertensive medication trials, in which the combination drug bisoprolol fumarate/hydrochlorothiazide (B/HT) was compared with placebo. The study comprised a 2-week single-blind placebo screening period, a 6-week double-blind dose titration period, a 4-week double-blind dose maintenance period, and a 2-week double-blind dose-tapering period. One hundred and forty subjects were enrolled to achieve 94 randomized subjects treated either with B/HT ( n=62) or placebo ( n=32). B/HT induced significant reductions compared with placebo for average sitting systolic blood pressure (SiSBP) (9.3 vs. 4.9 mmHg, P<0.05) and sitting diastolic blood pressure (SiDBP) (7.2 vs. 2.7 mmHg, P<0.05). The placebo-subtracted BP reductions were greater in younger children and those with more-severe baseline hypertension. The percentage of subjects with BP less than the 90th percentile at study completion was 45% for B/HT and 34% for placebo ( P=NS). Although the study demonstrated that B/HT reduced BP safely compared with placebo, the large placebo effect and failure of most subjects to achieve target BP control make it uncertain whether B/HT is appropriate first-line therapy for pediatric hypertension, particularly in adolescents with mild-to-moderate BP elevation.
Sorof
Jonathan M
JM
Division of Pediatric Nephrology and Hypertension, Medical School, University of Texas-Houston, 6431 Fannin Street, Room 3.124, Houston, TX 77030, USA. jonathan.m.sorof@uth.tmc.edu
Cargo
Paul
P
Graepel
Jay
J
Humphrey
David
D
King
Eileen
E
Rolf
Clyde
C
Cunningham
Robert J
RJ
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D017298:Bisoprolol / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002648:Child; D004232:Diuretics; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D010919:Placebos; D016037:Single-Blind Method; D049993:Sodium Chloride Symporter Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D017211:Treatment Failure
D000319:Adrenergic beta-Antagonists; D004232:Diuretics; D004338:Drug Combinations; D010919:Placebos; D049993:Sodium Chloride Symporter Inhibitors; D006852:Hydrochlorothiazide; D017298:Bisoprolol