Author + information
- John J.P. Kastelein,
- Meeike Kusters,
- Maria Caceres,
- Mauricio Coll,
- Cynthia Cuffie,
- Claude Gagné,
- Marc Jacobson,
- Peter Kwiterovich,
- Raymond Lee,
- Robert Lowe,
- Rachid Massaad,
- Brian McCrindle,
- Thomas Musliner and
- Joseph Triscari
For young children with high-risk dyslipidemia who do not achieve lipid targets with lifestyle intervention and where pharmacologic intervention is deemed necessary but statins are not suitable, ezetimibe (a cholesterol absorption inhibitor) may provide an alternative.
In a multicenter, 12 week, randomized, double blind, placebo controlled study, 138 children 6-10 years of age with diagnosed heterozygous familial hypercholesterolemia (HeFH) or clinically significant non-familial hypercholesterolemia (nonFH; LDL-C ≥160 mg/dL) were randomized 2:1 to ezetimibe 10mg (n=93) or placebo (n=45). Efficacy endpoints included % change from baseline to week 12 in LDL-C (primary) and other lipids/lipoproteins (secondary). Safety and tolerability were assessed in all treated patients.
Baseline demographics and lipids were similar between groups. Overall, mean age was 8.3 (±1.6) years, 57% were girls, 80% were white, mean baseline LDL-C was 228 mg/dL (±49), 91% had HeFH. After 12 weeks, ezetimibe significantly reduced LDL-C (27%, p<0.001) and other lipids/lipoproteins; HDL-C change was not significant (Table). Response in subgroups by gender, race, baseline lipids and HeFH/nonFH was generally consistent. Ezetimibe safety/tolerability profile was similar to studies in older children, adolescents, and adults.
In young children with HeFH or nonFH, ezetimibe monotherapy significantly reduced LDL-C and other key lipid parameters and was generally well tolerated.
|Lipid Parameter §||Ezetimibe N=85||Placebo N=42||% Difference|
|Baseline mg/dL (SD)||Week 12 % change||Baseline mg/dL (SD)||Week 12 % change|
|LDL-C||229 (46)||−28||222 (45)||−1||27**|
|Total Cholesterol||295 (48)||−21||290 (44)||<1||21**|
|HDL-C||50 (9)||2||50 (12)||1||1|
|Non-HDL-C||245 (47)||−25||240 (48)||<1||−26**|
|Triglycerides||82 (30)||−6||92 (61)||8||−15*,Δ|
|Apolipoprotein B||151 (29)||−22||148 (28)||−1||20**|
Numbers are rounded to no decimals for each metric separately. HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol
↵§ Percent changes from baseline is LS mean. LDL-C, Total cholesterol, HDL-C, non-HDL-C, analysis based on an ANCOVA mixed model with fixed effects for baseline lipid parameter, treatment (2 levels:ezetimibe 10 mg/day, placebo), gender, primary diagnosis (2 levels: HeFH, nonFH), study week (2, 4, 8 and 12), and treatment by study week interaction. Analysis of Apo B (with just one post-baseline measurement), excluded study week and treatment by study week interaction terms from the analysis model described above. Triglyceride analysis based on log-transformed data using a constrained LDA model with terms for treatment, gender, primary diagnosis, study week, and the interaction of treatment by study week. The difference in LS Means is based on the difference in the back transformed model-based LS means and the associated confidence interval is calculated using the Delta method.
↵Δ This was a nominally significant result; based on pre-specified multiplicity adjustment strategy, the triglyceride endpoint could not be declared statistically significant.
↵** p<0.001 for treatment differences
Poster Sessions, Expo North
Monday, March 11, 2013, 9:45 a.m.-10:30 a.m.
Session Title: Prevention: Treatment of Hyperlipidemia
Abstract Category: 24. Prevention: Clinical
Presentation Number: 1275-17
- 2013 American College of Cardiology Foundation