Title: Efficacy and Safety of Rosuvastatin Therapy for Children With Familial Hypercholesterolemia
Topic: Congenital Heart Disease
Date Posted: 3/8/2010 5:00:00 PM
Author(s): Avis HJ, Hutten BA, Gagne C, et al.
Citation: J Am Coll Cardiol 2010;55:1121-1126.
Clinical Trial: yes
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JACC Article: Efficacy and Safety of Rosuvastatin Therapy for Children With Familial Hypercholesterolemia
Study Question: What is the safety and efficacy of rosuvastatin therapy for children with familial hypercholesterolemia?
Methods: A 12-week, double-blind, randomized, placebo-controlled trial was performed, followed by a 40-week open-label extension phase. A total of 177 children (mean age 14.5 years) were enrolled, and were randomized either to placebo or rosuvastatin 5, 10, or 20 mg daily.
Results: Low-density lipoprotein cholesterol (LDL-C) reduction with 5, 10, and 20 mg of rosuvastatin was 38%, 45%, and 50%, respectively, as compared with placebo. During the open-label phase, maximum dosing of 20 mg daily resulted in 40% of patients achieving the treatment goal LDL-C of <110 mg/dl. No impact on growth or development was seen.
Conclusions: In children with familial hypercholesterolemia, rosuvastatin 20 mg resulted in LDL-C reductions of 50%. A minority of patients achieved the LDL-C target of 110 mg/dl, consistent with the high baseline LDL-C in this patient population.
Perspective: Familial hypercholesterolemia is associated with early atherosclerosis and cardiovascular events. This study demonstrates efficacy of the high potency HMG-CoA reductase inhibitor rosuvastatin in reducing LDL-C levels in adolescents. Despite a 50% reduction in LDL-C, a minority of patients reached the goal LDL-C, in large part due to the high baseline LDL-C level of 228-239 mg/dl. Compliance was an issue in the open-label extension of this study, with 60% of patients maintaining ≥80% compliance with the study drug. This is reflective of the challenge of compliance with drug therapy in adolescents. The long-term safety of these agents in adolescents has not yet been reported. Timothy B. Cotts, M.D., F.A.C.C.
Title: Cardiovascular Manifestations of Fabry Disease: Relationships Between Left Ventricular Hypertrophy, Disease Severity, and α-galactosidase A Activity
Topic: Congenital Heart Disease
Date Posted: 3/2/2010
Author(s): Wu JC, Ho CY, Skali H, et al.
Citation: Eur Heart J 2010;Jan 7:[Epub ahead of print].
Clinical Trial: No
Study Question: In patients with Fabry disease, what are the relationships between disease severity, α-galactosidase A (α-gal) activity, and cardiac abnormalities?
Methods: A prospective analysis of patients undergoing screening for clinical trials of enzyme replacement therapy was performed. Baseline echocardiograms, electrocardiograms, exams, basic laboratory studies, and α-gal activity were analyzed.
Results: A total of 139 patients (92 males and 47 females) were studied. Cardiovascular symptoms were reported in 60.4% of patients, while 84.8% of patients showed concentric left ventricular hypertrophy (LVH). In females, log-corrected α-gal activity was inversely associated with LV mass index (r = -0.45, p < 0.040). The most LVH and cardiac symptoms were seen in males with low α-gal activity, although LVH was present in females less than 20 years old.
Conclusions: Concentric LVH was the prominent cardiac pathology in patients with Fabry disease, occurring even in young females.
Perspective: Fabry disease is a rare X-linked recessive lysosomal storage disorder associated with infiltrative and occlusive disease of the heart, kidney, and in the brain. This study documents cardiac involvement in patients under consideration for enrollment in enzyme replacement therapy studies. As one of the studies required moderate renal dysfunction for participation, this analysis may have selected patients with more advanced disease. As even relatively young patients were seen to have cardiac involvement, there may be a role for early enzyme replacement therapy to positively impact the natural history of cardiac involvement. Timothy B. Cotts, M.D., F.A.C.C.