Colesevelam hydrochloride: efficacy and safety in pediatric subjects with heterozygous familial hypercholesterolemia.

OBJECTIVE: Evaluate the efficacy and safety of colesevelam hydrochloride in children with heterozygous familial hypercholesterolemia (heFH). STUDY DESIGN: This was a randomized, double-blind, 41-site study in 194 children aged 10 to 17 years (inclusive) with heFH (statin-naïve or on a stable statin regimen). After a 4-week stabilization period (period I), subjects were randomized 1:1:1 to placebo, colesevelam 1.875 g/d, or colesevelam 3.75 g/d for 8 weeks (period II). All then received open-label colesevelam 3.75 g/d for 18 weeks (period III), with follow-up 2 weeks later. The primary endpoint was percent change in low-density lipoprotein (LDL)-cholesterol from baseline to week 8. Secondary endpoints included percent change in other lipoprotein variables, including non-high-density lipoprotein (non-HDL)-cholesterol. Adverse events were also evaluated. RESULTS: At week 8, a significant difference from baseline in LDL-cholesterol was reported with colesevelam 1.875 g/d (-6.3%; P = .031) and colesevelam 3.75 g/d (-12.5%; P < .001) compared with placebo. Significant treatment effects were also reported for total cholesterol (-7.4%), non-HDL-cholesterol (-10.9%), HDL-cholesterol (+6.1%), apolipoprotein A-I (+6.9%), and apolipoprotein B (-8.3%) and a nonsignificant effect for triglycerides (+5.1%) with colesevelam 3.75 g/d compared with placebo at week 8. These treatment effects were maintained during period III. CONCLUSIONS: Colesevelam significantly lowered LDL-cholesterol levels in children with heFH.

Achieving LDL cholesterol, non-HDL cholesterol, and apolipoprotein B target levels in high-risk patients: measuring effective reductions in cholesterol using rosuvastatin therapY (MERCURY) II

Background National Cholesterol Education Program Adult Treatment Panel III guidelines for patients at a high risk of coronary heart disease set a low-density lipoprotein cholesterol (LDL-C) target of b100 mg/dL. This target can be difficult to attain with diet and current therapy. Methods In a 16-week multinational trial, 1993 high-risk patients were randomized to rosuvastatin 20 mg, atorvastatin 10 mg, atorvastatin 20 mg, simvastatin 20 mg, or simvastatin 40 mg for 8 weeks. Patients either remained on starting treatment or switched to lower or milligram-equivalent doses of rosuvastatin for 8 more weeks. Results At 16 weeks, more patients achieved their LDL-C target by switching to rosuvastatin 10 mg than staying on atorvastatin 10 mg (66% vs 42%, P b .001) or simvastatin 20 mg (73% vs 32%, P b .001). Changing to rosuvastatin 20 mg brought more patients to their LDL-C target than staying on atorvastatin 20 mg (79% vs 64%, P b .001) or simvastatin 40 mg (84% vs 56%, P b .001). More very high risk patients achieved an LDL-C target of b70 mg/dL when changed to rosuvastatin from atorvastatin or simvastatin (within-arm comparisons P b .01). More hypertriglyceridemic patients (triglycerides z200 mg/dL) met LDL-C, non–high-density lipoprotein cholesterol (non–HDL-C), and apolipoprotein B targets by changing to rosuvastatin. Switching to rosuvastatin produced greater reductions in LDL-C, total cholesterol, non–HDL-C, apolipoprotein B, and lipid ratios. All treatments were well tolerated, with no differences among treatment groups in skeletal muscle, hepatic, or renal toxicity. Conclusion Rosuvastatin 10 or 20 mg is an effective and safe therapeutic option for high-risk patients to achieve their lipid and apolipoprotein targets.