Rosuvastatin safe, effective in adolescents

Rosuvastatin successfully lowered LDL levels and demonstrated a favorable safety profile after one year among children aged 10 to 17 years who had familial hypercholesterolemia, findings from the PLUTO trial indicated.

“This study is the first to our knowledge to evaluate the efficacy and safety of rosuvastatin [Crestor, AstraZeneca] in a pediatric population,” the researchers wrote.

They enrolled 177 pubertal children from 20 centers in North America and Europe and randomly assigned them to either placebo or one of three once-daily doses of rosuvastatin (5 mg, 10 mg or 20 mg; 1:1:1:1). Patients who participated in the trial met the following inclusion criteria:

Heterozygous familial hypercholesterolemia identified by genetic defect or predefined clinical criteria.
Tanner stage >II; girls at least one year post-menarche.
Fasting LDL >190 mg/dL, LDL >160 mg/dL with a family history of premature cardiovascular disease or at least two other risk factors for CVD.

The researchers measured the LDL percentage change from baseline (mean, 232 mg/dL) to the end of the 12-week, double blind phase of the trial and found that patients assigned to rosuvastatin experienced reductions in LDL compared with those assigned to placebo (5 mg, 38%; 10 mg, 45%; 20 mg, 50%).

Among the 164 patients who completed a second 40-week, open-label, dose-titration phase, 40% reached the LDL treatment goal of <110 mg/dL (5 mg, n=26; 10 mg, n=25; 20 mg, n=122). Assessing pill counts, the researchers estimated that approximately 90% of patients in the double blind phase and 60% of patients in the open-label phase maintained a >80% compliance to the study medication. Adverse event rates were similar among patients in both study groups — with the most common being headache, nasopharyngitis, influenza, myalgia and nausea — and growth and development progressed normally, according to the researchers.

“The [LDL] reductions observed with these rosuvastatin doses in this study are consistent with those seen in adults, and at the 20-mg dose are the largest reported in [children with familial hypercholesterolemia] to date with any statin,” the researchers wrote.

The researchers also noted that 60% of patients were unable to reach the LDL treatment goal, highlighting the difficulty of maintaining optimal LDL in adolescents with familial hypercholesterolemia. According to the researchers, future studies are needed to assess long-term safety and the potential for more rare or subtle adverse events.

Avis HJ. J Am Coll Cardiol. 2010;55:1121-1126.