Abstract 15499: Low-Density Lipoprotein Cholesterol Response With Rosuvastatin in Children and Adults With Homozygous Familial Hypercholesterolemia as It Relates to Underlying Genetic Mutations

Abstract 15499: Low-Density Lipoprotein Cholesterol Response With Rosuvastatin in Children and Adults With Homozygous Familial Hypercholesterolemia as It Relates to Underlying Genetic Mutations

IntroductionStatins are the first line of therapy in the treatment of homozygous familial hypercholesterolemia (HoFH), a rare genetic disorder with extremely elevated LDL-C which leads to premature, aggressive atherosclerosis. The genetic mutations causing HoFH vary considerably, as does response to...

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Veröffentlicht in:Circulation (New York, N.Y.) N.Y.), 2016-11, Vol.134 (Suppl_1 Suppl 1), p.A15499-A15499
Hauptverfasser: Stein, Evan A, Raal, Frederick J, Raichlen, Joel S, Carlsson, Stefan C, Blasetto, James W, Sundén, Mattias, Kastelein, John J
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container_issue Suppl_1 Suppl 1
container_start_page A15499
container_title Circulation (New York, N.Y.)
container_volume 134
creator Stein, Evan A
Raal, Frederick J
Raichlen, Joel S
Carlsson, Stefan C
Blasetto, James W
Sundén, Mattias
Kastelein, John J
description IntroductionStatins are the first line of therapy in the treatment of homozygous familial hypercholesterolemia (HoFH), a rare genetic disorder with extremely elevated LDL-C which leads to premature, aggressive atherosclerosis. The genetic mutations causing HoFH vary considerably, as does response to statin therapy. We examine the association between age, HoFH genotypes and the response to rosuvastatin treatment.MethodsWe combined data from two trials of HoFH patients confirmed by genetic or clinical criteriaa pediatric trial of 13 HoFH patients aged 7 to 15 years who completed a randomized, double-blind, 6 week study of rosuvastatin 20 mg daily, preceded or followed by 6 weeks of placebo. Patients had discontinued all lipid-lowering medication except ezetimibe and/or apheresis. The other study included 40 HoFH patients, 7 aged
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The genetic mutations causing HoFH vary considerably, as does response to statin therapy. We examine the association between age, HoFH genotypes and the response to rosuvastatin treatment.MethodsWe combined data from two trials of HoFH patients confirmed by genetic or clinical criteriaa pediatric trial of 13 HoFH patients aged 7 to 15 years who completed a randomized, double-blind, 6 week study of rosuvastatin 20 mg daily, preceded or followed by 6 weeks of placebo. Patients had discontinued all lipid-lowering medication except ezetimibe and/or apheresis. The other study included 40 HoFH patients, 7 aged &lt;18 years, and 33 adults aged 18 to 63 years. All were diet stable prior to 6 weeks of treatment with rosuvastatin 20 mg daily. At baseline and the end of each treatment, clinical and laboratory assessments were performed.ResultsOf the 53 patients, mean ± SD age 24.0 ± 12.4 years, 57% were males, 8 were on ezetimibe, and 14 were receiving apheresis. Baseline LDL-C was 507.5 ± 135.2 mg/dL. Rosuvastatin 20 mg daily reduced LDL-C a mean of 99.4 mg/dL (20.3 ± 13.6%; p&lt;0.001). The LDL-C reductions based on age &lt;/≥18 years and LDL receptor (LDLR) subgroups are shown in the Table. There were no treatment related adverse events during the study period. Two patients had SAEs and 19 had AEs during treatment; 11 had AEs during the statin free period.ConclusionsThese data confirm good safety and clinically significant LDL-C lowering with rosuvastatin in pediatric and adult HoFH patients. It also demonstrates that the underlying LDLR mutations impact LDL-C response but, unlike PCSK9 inhibitors, even patients with LDLR negative mutations show some reduction, likely due to reduction in cholesterol synthesis by HMG CoA reductase inhibition.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><language>eng</language><publisher>by the American College of Cardiology Foundation and the American Heart Association, Inc</publisher><ispartof>Circulation (New York, N.Y.), 2016-11, Vol.134 (Suppl_1 Suppl 1), p.A15499-A15499</ispartof><rights>2016 by the American College of Cardiology Foundation and the American Heart Association, Inc.</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780</link.rule.ids></links><search><creatorcontrib>Stein, Evan A</creatorcontrib><creatorcontrib>Raal, Frederick J</creatorcontrib><creatorcontrib>Raichlen, Joel S</creatorcontrib><creatorcontrib>Carlsson, Stefan C</creatorcontrib><creatorcontrib>Blasetto, James W</creatorcontrib><creatorcontrib>Sundén, Mattias</creatorcontrib><creatorcontrib>Kastelein, John J</creatorcontrib><title>Abstract 15499: Low-Density Lipoprotein Cholesterol Response With Rosuvastatin in Children and Adults With Homozygous Familial Hypercholesterolemia as It Relates to Underlying Genetic Mutations</title><title>Circulation (New York, N.Y.)</title><description>IntroductionStatins are the first line of therapy in the treatment of homozygous familial hypercholesterolemia (HoFH), a rare genetic disorder with extremely elevated LDL-C which leads to premature, aggressive atherosclerosis. The genetic mutations causing HoFH vary considerably, as does response to statin therapy. We examine the association between age, HoFH genotypes and the response to rosuvastatin treatment.MethodsWe combined data from two trials of HoFH patients confirmed by genetic or clinical criteriaa pediatric trial of 13 HoFH patients aged 7 to 15 years who completed a randomized, double-blind, 6 week study of rosuvastatin 20 mg daily, preceded or followed by 6 weeks of placebo. Patients had discontinued all lipid-lowering medication except ezetimibe and/or apheresis. The other study included 40 HoFH patients, 7 aged &lt;18 years, and 33 adults aged 18 to 63 years. All were diet stable prior to 6 weeks of treatment with rosuvastatin 20 mg daily. At baseline and the end of each treatment, clinical and laboratory assessments were performed.ResultsOf the 53 patients, mean ± SD age 24.0 ± 12.4 years, 57% were males, 8 were on ezetimibe, and 14 were receiving apheresis. Baseline LDL-C was 507.5 ± 135.2 mg/dL. Rosuvastatin 20 mg daily reduced LDL-C a mean of 99.4 mg/dL (20.3 ± 13.6%; p&lt;0.001). The LDL-C reductions based on age &lt;/≥18 years and LDL receptor (LDLR) subgroups are shown in the Table. There were no treatment related adverse events during the study period. Two patients had SAEs and 19 had AEs during treatment; 11 had AEs during the statin free period.ConclusionsThese data confirm good safety and clinically significant LDL-C lowering with rosuvastatin in pediatric and adult HoFH patients. It also demonstrates that the underlying LDLR mutations impact LDL-C response but, unlike PCSK9 inhibitors, even patients with LDLR negative mutations show some reduction, likely due to reduction in cholesterol synthesis by HMG CoA reductase inhibition.</description><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid/><recordid>eNqdj01KxEAQhYMoGH_uUBcIdNL5Ie6G0THCuBkUl0OblJPWTnfoqjjE23kze1Rwb20eBV-99-ooitMiy5O8kPVxFAsh6qSSWXYanRG9hrWUVRFHn4tnYq9ahrTI6_oK1m6fXKMlzTOs9ehG7xi1hWXvDBKjdwY2SKOzhPCkuYeNo-ldESsO2DepTefRgrIdLLrJMP2AjRvcx7xzE8FKDdpoZaCZR_TtnzcOWoEiuOOQYhQjATt4tB16M2u7g1u0yLqF--kQGFpcRCcvyhBe_up5lK9uHpZNsncmWNKbmfbotz0qw_02PC6kSKskE2mZHiYRqaxK-c-zL0fNceo</recordid><startdate>20161111</startdate><enddate>20161111</enddate><creator>Stein, Evan A</creator><creator>Raal, Frederick J</creator><creator>Raichlen, Joel S</creator><creator>Carlsson, Stefan C</creator><creator>Blasetto, James W</creator><creator>Sundén, Mattias</creator><creator>Kastelein, John J</creator><general>by the American College of Cardiology Foundation and the American Heart Association, Inc</general><scope/></search><sort><creationdate>20161111</creationdate><title>Abstract 15499: Low-Density Lipoprotein Cholesterol Response With Rosuvastatin in Children and Adults With Homozygous Familial Hypercholesterolemia as It Relates to Underlying Genetic Mutations</title><author>Stein, Evan A ; Raal, Frederick J ; Raichlen, Joel S ; Carlsson, Stefan C ; Blasetto, James W ; Sundén, Mattias ; Kastelein, John J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-wolterskluwer_health_00003017-201611111-013763</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><toplevel>online_resources</toplevel><creatorcontrib>Stein, Evan A</creatorcontrib><creatorcontrib>Raal, Frederick J</creatorcontrib><creatorcontrib>Raichlen, Joel S</creatorcontrib><creatorcontrib>Carlsson, Stefan C</creatorcontrib><creatorcontrib>Blasetto, James W</creatorcontrib><creatorcontrib>Sundén, Mattias</creatorcontrib><creatorcontrib>Kastelein, John J</creatorcontrib><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stein, Evan A</au><au>Raal, Frederick J</au><au>Raichlen, Joel S</au><au>Carlsson, Stefan C</au><au>Blasetto, James W</au><au>Sundén, Mattias</au><au>Kastelein, John J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Abstract 15499: Low-Density Lipoprotein Cholesterol Response With Rosuvastatin in Children and Adults With Homozygous Familial Hypercholesterolemia as It Relates to Underlying Genetic Mutations</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><date>2016-11-11</date><risdate>2016</risdate><volume>134</volume><issue>Suppl_1 Suppl 1</issue><spage>A15499</spage><epage>A15499</epage><pages>A15499-A15499</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><abstract>IntroductionStatins are the first line of therapy in the treatment of homozygous familial hypercholesterolemia (HoFH), a rare genetic disorder with extremely elevated LDL-C which leads to premature, aggressive atherosclerosis. The genetic mutations causing HoFH vary considerably, as does response to statin therapy. We examine the association between age, HoFH genotypes and the response to rosuvastatin treatment.MethodsWe combined data from two trials of HoFH patients confirmed by genetic or clinical criteriaa pediatric trial of 13 HoFH patients aged 7 to 15 years who completed a randomized, double-blind, 6 week study of rosuvastatin 20 mg daily, preceded or followed by 6 weeks of placebo. Patients had discontinued all lipid-lowering medication except ezetimibe and/or apheresis. The other study included 40 HoFH patients, 7 aged &lt;18 years, and 33 adults aged 18 to 63 years. All were diet stable prior to 6 weeks of treatment with rosuvastatin 20 mg daily. At baseline and the end of each treatment, clinical and laboratory assessments were performed.ResultsOf the 53 patients, mean ± SD age 24.0 ± 12.4 years, 57% were males, 8 were on ezetimibe, and 14 were receiving apheresis. Baseline LDL-C was 507.5 ± 135.2 mg/dL. Rosuvastatin 20 mg daily reduced LDL-C a mean of 99.4 mg/dL (20.3 ± 13.6%; p&lt;0.001). The LDL-C reductions based on age &lt;/≥18 years and LDL receptor (LDLR) subgroups are shown in the Table. There were no treatment related adverse events during the study period. Two patients had SAEs and 19 had AEs during treatment; 11 had AEs during the statin free period.ConclusionsThese data confirm good safety and clinically significant LDL-C lowering with rosuvastatin in pediatric and adult HoFH patients. It also demonstrates that the underlying LDLR mutations impact LDL-C response but, unlike PCSK9 inhibitors, even patients with LDLR negative mutations show some reduction, likely due to reduction in cholesterol synthesis by HMG CoA reductase inhibition.</abstract><pub>by the American College of Cardiology Foundation and the American Heart Association, Inc</pub></addata></record>
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title Abstract 15499: Low-Density Lipoprotein Cholesterol Response With Rosuvastatin in Children and Adults With Homozygous Familial Hypercholesterolemia as It Relates to Underlying Genetic Mutations
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