An eight-week trial investigating the efficacy and tolerability of atorvastatin for children and adolescents with heterozygous familial hypercholesterolemia.
This study aimed to assess the efficacy and tolerability of atorvastatin in Tanner stage (TS) 1 patients ages 6 to 10 years and TS ≥ 2 patients ages 10 to <18 years with genetically confirmed heterozygous familial hypercholesterolemia (HeFH) and a low density lipoprotein cholesterol (LDL-C) level of 4 mmol/l (155 mg/dl) or higher. In this open-label, 8-week study, 15 TS 1 children were treated initially with atorvastatin 5 mg/day and 24 TS ≥ 2 children with 10 mg/day. Doses were doubled at week 4 if the LDL-C target (<3.35 mmol/l [130 mg/dl]) was not achieved. The efficacy variables were the percentage change from baseline in LDL-C, total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), very low density lipoprotein cholesterol (VLDL-C), and apolipoprotein (Apo) A-I and Apo B. Safety evaluations included clinical monitoring, subject-reported adverse events (AEs), vital signs, and clinical laboratory tests. The mean values for LDL-C, TC, VLDL-C, and Apo B decreased by week 2 among all TS 1 and TS ≥ 2 patients, whereas TG, HDL-C, and Apo A-I varied considerably from week to week. After 8 weeks, the mean reduction in LDL-C was -40.7% ± 8.4 for the TS 1 children and -39.7% ± 10.3 for the TS ≥ 2 children. For the TS 1 patients, the mean reductions were -34.1% ± 6.9 for TC and -6.0% ± 32.1 for TG. The corresponding changes for the TS ≥ 2 patients were -35.6% ± 9.5 for TC and -21.1% ± 29.7 for TG. Four patients experienced mild to moderate treatment-related AEs. No serious AEs or discontinuations were reported. Overall, no difference in safety or tolerability was observed between the younger and older cohorts. Across the range of exposures after atorvastatin 5 to 10 mg (TS 1) or atorvastatin 10 to 20 mg (TS ≥ 2) doses for 8 weeks, clinically meaningful reductions in LDL-C, TC, VLDL-C, and Apo were observed with atorvastatin in pediatric patients who had HeFH. Atorvastatin also was well tolerated in this population.
Pfizer Inc, 235 East 42nd Street, New York, NY 10017, USA. kuan.gandelman@pfizer.com
Kuan
K
Gandelman
Paul
P
Glue
Rachel
R
Laskey
Jonathan
J
Jones
Robert
R
LaBadie
Leiv
L
Ose
D000293:Adolescent; D000069059:Atorvastatin; D002648:Child; D008076:Cholesterol, HDL / Q000097:blood* / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood* / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005260:Female; D005500:Follow-Up Studies; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D006579:Heterozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*; D012189:Retrospective Studies; D016896:Treatment Outcome
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin
Circulation. 2007 Apr 10;115(14):1948-67
17377073
J Clin Pharmacol. 2013 May;53(5):505-16
23381936
Circulation. 2002 Oct 22;106(17):2231-7
12390953
J Pediatr. 2003 Jul;143(1):74-80
12915827
Pediatr Res. 1996 May;39(5):867-71
8726243
J Am Coll Cardiol. 2002 Dec 18;40(12):2117-21
12505222
JAMA. 2004 Jul 21;292(3):331-7
15265847
N Engl J Med. 1986 Apr 3;314(14):879-83
3633381
Pediatrics. 2008 Jul;122(1):198-208
18596007
Pediatrics. 2005 Sep;116(3):682-8
16140708
J Am Coll Cardiol. 2002 Jan 16;39(2):257-65
11788217
N Engl J Med. 2008 Sep 25;359(13):1309-12
18815394
Circulation. 2007 Aug 7;116(6):664-8
17664376
Arch Dis Child. 2010 Sep;95(9):673-80
20515970
Ann Med. 2001 Sep;33(6):410-21
11585102
JAMA. 1999 Jan 13;281(2):137-44
9917116