Reductions in serum levels of LDL cholesterol, apolipoprotein B, triglycerides and lipoprotein(a) in hypercholesterolaemic patients treated with the liver‐selective thyroid hormone receptor agonist eprotirome
Background Liver‐selective thyromimetic agents could provide a new approach for treating dyslipidaemia. Methods We performed a multicentre, randomized, placebo‐controlled, double‐blind study to evaluate the efficacy and safety of eprotirome, a liver‐selective thyroid hormone receptor agonist, in 98...
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| Veröffentlicht in: | Journal of internal medicine 2015-03, Vol.277 (3), p.331-342 |
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| creator | Angelin, Bo Kristensen, Jens D. Eriksson, Mats Carlsson, Bo Klein, Irwin Olsson, Anders G. Chester Ridgway, E. Ladenson, Paul W. |
| description | Background
Liver‐selective thyromimetic agents could provide a new approach for treating dyslipidaemia.
Methods
We performed a multicentre, randomized, placebo‐controlled, double‐blind study to evaluate the efficacy and safety of eprotirome, a liver‐selective thyroid hormone receptor agonist, in 98 patients with primary hypercholesterolaemia. After previous drug wash‐out and dietary run‐in, patients received 100 or 200 μg day−1 eprotirome or placebo for 12 weeks. The primary end‐point was change in serum LDL cholesterol; secondary end‐points included changes in other lipid parameters and safety measures.
Results
Eprotirome treatment at 100 and 200 μg daily reduced serum LDL cholesterol levels by 23 ± 5% and 31 ± 4%, respectively, compared with 2 ± 6% for placebo (P |
| doi_str_mv | 10.1111/joim.12261 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_swepub_ki_se_522072</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1655521589</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5891-9906c5f50c2c3c113120fd8e0e786773ee6f0cfaa0994c59cb510f84417f24af3</originalsourceid><addsrcrecordid>eNp9ks1uEzEQgFcIREPhwgMgS1wK6haPd70_x9LyUxRUCQFXy_HOJg7e9db2JsqNR-DZeASeBIekpUKivtgaffPNaDxJ8hToCcTzaml1dwKMFXAvmUBW8JSVdXE_mdCa52lRMXqQPPJ-SSlktKAPkwOWlzzPIJskPz9hM6qgbe-J7olHN3bE4AqNJ7Yl0_MpUQtr0Ad01hwTOVijBzs4GzDyr49JcHpuNgqdbtAT2TfkFnAkX2y1i82A7pZHYqcVGWTQ2AcfFSgDNmStw4KEBUbDCt2v7z88GozNrTBGN87qhiys62yPxKHCIVhH5Nz22geC24ra2Q4fJw9aaTw-2d-HyZe3bz6fvU-nl-8uzk6nqeJVDWld00LxllPFVKYAMmC0bSqkWFZFWWaIRUtVKyWt61zxWs040LbKcyhblss2O0zSndevcRhnYnC6k24jrNRiH_oWXyg4Y7Rkka__y8fmm79J14nxu8qSZ6y4s9a5_noqrJsLo0cBUHDIIn-046P4aoxTF532Co2RPdrRi0hxziAOIqLP_0GXdnR9nJyAuoKcAq1opF7uKOWs9w7bmxaAiu0Wiu0Wij9bGOFne-U467C5Qa_XLgKwA9ba4OYOlfhwefFxJ_0Nl5bvww</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1981401080</pqid></control><display><type>article</type><title>Reductions in serum levels of LDL cholesterol, apolipoprotein B, triglycerides and lipoprotein(a) in hypercholesterolaemic patients treated with the liver‐selective thyroid hormone receptor agonist eprotirome</title><source>Wiley Online Library website</source><source>MEDLINE</source><source>Free E-Journal (出版社公開部分のみ）</source><source>Wiley Blackwell Journals</source><creator>Angelin, Bo ; Kristensen, Jens D. ; Eriksson, Mats ; Carlsson, Bo ; Klein, Irwin ; Olsson, Anders G. ; Chester Ridgway, E. ; Ladenson, Paul W.</creator><creatorcontrib>Angelin, Bo ; Kristensen, Jens D. ; Eriksson, Mats ; Carlsson, Bo ; Klein, Irwin ; Olsson, Anders G. ; Chester Ridgway, E. ; Ladenson, Paul W.</creatorcontrib><description>Background
Liver‐selective thyromimetic agents could provide a new approach for treating dyslipidaemia.
Methods
We performed a multicentre, randomized, placebo‐controlled, double‐blind study to evaluate the efficacy and safety of eprotirome, a liver‐selective thyroid hormone receptor agonist, in 98 patients with primary hypercholesterolaemia. After previous drug wash‐out and dietary run‐in, patients received 100 or 200 μg day−1 eprotirome or placebo for 12 weeks. The primary end‐point was change in serum LDL cholesterol; secondary end‐points included changes in other lipid parameters and safety measures.
Results
Eprotirome treatment at 100 and 200 μg daily reduced serum LDL cholesterol levels by 23 ± 5% and 31 ± 4%, respectively, compared with 2 ± 6% for placebo (P < 0.0001). Similar reductions were seen in non‐HDL cholesterol and apolipoprotein (apo) B, whereas serum levels of HDL cholesterol and apo A‐I were unchanged. There were also considerable reductions in serum triglycerides and lipoprotein(a), in particular in patients with elevated levels at baseline. There was no evidence of adverse effects on heart or bone and no changes in serum thyrotropin or triiodothyronine, although the thyroxine level decreased. Low‐grade increases in liver enzymes were evident in most patients.
Conclusion
In hypercholesterolaemic patients, the liver‐selective thyromimetic eprotirome decreased serum levels of atherogenic lipoproteins without signs of extra‐hepatic side effects. Selective stimulation of hepatic thyroid hormone receptors may be an attractive way to modulate lipid metabolism in hyperlipidaemia.</description><identifier>ISSN: 0954-6820</identifier><identifier>ISSN: 1365-2796</identifier><identifier>EISSN: 1365-2796</identifier><identifier>DOI: 10.1111/joim.12261</identifier><identifier>PMID: 24754313</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Anilides - administration & dosage ; Anilides - adverse effects ; Anticholesteremic Agents - administration & dosage ; Anticholesteremic Agents - adverse effects ; Apolipoproteins ; Apolipoproteins B - drug effects ; Blood Pressure - drug effects ; Bone and Bones - metabolism ; Cholesterol ; Cholesterol, LDL - drug effects ; Double-Blind Method ; Drug Administration Schedule ; Dyslipidemia ; Female ; Heart Rate - drug effects ; Humans ; hypercholesterolaemia ; Hypercholesterolemia - blood ; Hypercholesterolemia - drug therapy ; Levels ; Lipid metabolism ; Lipids ; lipoprotein ; Lipoprotein(a) - blood ; Lipoproteins ; Liver ; Low density lipoprotein ; Male ; Medicin och hälsovetenskap ; Middle Aged ; Receptors ; Safety measures ; Side effects ; thyroid ; Thyroid gland ; Thyrotropin - metabolism ; Thyroxine ; Triglycerides ; Triglycerides - blood ; Triiodothyronine - metabolism</subject><ispartof>Journal of internal medicine, 2015-03, Vol.277 (3), p.331-342</ispartof><rights>2014 The Association for the Publication of the Journal of Internal Medicine</rights><rights>2014 The Association for the Publication of the Journal of Internal Medicine.</rights><rights>Copyright © 2015 The Association for the Publication of the Journal of Internal Medicine</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5891-9906c5f50c2c3c113120fd8e0e786773ee6f0cfaa0994c59cb510f84417f24af3</citedby><cites>FETCH-LOGICAL-c5891-9906c5f50c2c3c113120fd8e0e786773ee6f0cfaa0994c59cb510f84417f24af3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjoim.12261$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjoim.12261$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24754313$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-116513$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:130775326$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Angelin, Bo</creatorcontrib><creatorcontrib>Kristensen, Jens D.</creatorcontrib><creatorcontrib>Eriksson, Mats</creatorcontrib><creatorcontrib>Carlsson, Bo</creatorcontrib><creatorcontrib>Klein, Irwin</creatorcontrib><creatorcontrib>Olsson, Anders G.</creatorcontrib><creatorcontrib>Chester Ridgway, E.</creatorcontrib><creatorcontrib>Ladenson, Paul W.</creatorcontrib><title>Reductions in serum levels of LDL cholesterol, apolipoprotein B, triglycerides and lipoprotein(a) in hypercholesterolaemic patients treated with the liver‐selective thyroid hormone receptor agonist eprotirome</title><title>Journal of internal medicine</title><addtitle>J Intern Med</addtitle><description>Background
Liver‐selective thyromimetic agents could provide a new approach for treating dyslipidaemia.
Methods
We performed a multicentre, randomized, placebo‐controlled, double‐blind study to evaluate the efficacy and safety of eprotirome, a liver‐selective thyroid hormone receptor agonist, in 98 patients with primary hypercholesterolaemia. After previous drug wash‐out and dietary run‐in, patients received 100 or 200 μg day−1 eprotirome or placebo for 12 weeks. The primary end‐point was change in serum LDL cholesterol; secondary end‐points included changes in other lipid parameters and safety measures.
Results
Eprotirome treatment at 100 and 200 μg daily reduced serum LDL cholesterol levels by 23 ± 5% and 31 ± 4%, respectively, compared with 2 ± 6% for placebo (P < 0.0001). Similar reductions were seen in non‐HDL cholesterol and apolipoprotein (apo) B, whereas serum levels of HDL cholesterol and apo A‐I were unchanged. There were also considerable reductions in serum triglycerides and lipoprotein(a), in particular in patients with elevated levels at baseline. There was no evidence of adverse effects on heart or bone and no changes in serum thyrotropin or triiodothyronine, although the thyroxine level decreased. Low‐grade increases in liver enzymes were evident in most patients.
Conclusion
In hypercholesterolaemic patients, the liver‐selective thyromimetic eprotirome decreased serum levels of atherogenic lipoproteins without signs of extra‐hepatic side effects. Selective stimulation of hepatic thyroid hormone receptors may be an attractive way to modulate lipid metabolism in hyperlipidaemia.</description><subject>Anilides - administration & dosage</subject><subject>Anilides - adverse effects</subject><subject>Anticholesteremic Agents - administration & dosage</subject><subject>Anticholesteremic Agents - adverse effects</subject><subject>Apolipoproteins</subject><subject>Apolipoproteins B - drug effects</subject><subject>Blood Pressure - drug effects</subject><subject>Bone and Bones - metabolism</subject><subject>Cholesterol</subject><subject>Cholesterol, LDL - drug effects</subject><subject>Double-Blind Method</subject><subject>Drug Administration Schedule</subject><subject>Dyslipidemia</subject><subject>Female</subject><subject>Heart Rate - drug effects</subject><subject>Humans</subject><subject>hypercholesterolaemia</subject><subject>Hypercholesterolemia - blood</subject><subject>Hypercholesterolemia - drug therapy</subject><subject>Levels</subject><subject>Lipid metabolism</subject><subject>Lipids</subject><subject>lipoprotein</subject><subject>Lipoprotein(a) - blood</subject><subject>Lipoproteins</subject><subject>Liver</subject><subject>Low density lipoprotein</subject><subject>Male</subject><subject>Medicin och hälsovetenskap</subject><subject>Middle Aged</subject><subject>Receptors</subject><subject>Safety measures</subject><subject>Side effects</subject><subject>thyroid</subject><subject>Thyroid gland</subject><subject>Thyrotropin - metabolism</subject><subject>Thyroxine</subject><subject>Triglycerides</subject><subject>Triglycerides - blood</subject><subject>Triiodothyronine - metabolism</subject><issn>0954-6820</issn><issn>1365-2796</issn><issn>1365-2796</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9ks1uEzEQgFcIREPhwgMgS1wK6haPd70_x9LyUxRUCQFXy_HOJg7e9db2JsqNR-DZeASeBIekpUKivtgaffPNaDxJ8hToCcTzaml1dwKMFXAvmUBW8JSVdXE_mdCa52lRMXqQPPJ-SSlktKAPkwOWlzzPIJskPz9hM6qgbe-J7olHN3bE4AqNJ7Yl0_MpUQtr0Ad01hwTOVijBzs4GzDyr49JcHpuNgqdbtAT2TfkFnAkX2y1i82A7pZHYqcVGWTQ2AcfFSgDNmStw4KEBUbDCt2v7z88GozNrTBGN87qhiys62yPxKHCIVhH5Nz22geC24ra2Q4fJw9aaTw-2d-HyZe3bz6fvU-nl-8uzk6nqeJVDWld00LxllPFVKYAMmC0bSqkWFZFWWaIRUtVKyWt61zxWs040LbKcyhblss2O0zSndevcRhnYnC6k24jrNRiH_oWXyg4Y7Rkka__y8fmm79J14nxu8qSZ6y4s9a5_noqrJsLo0cBUHDIIn-046P4aoxTF532Co2RPdrRi0hxziAOIqLP_0GXdnR9nJyAuoKcAq1opF7uKOWs9w7bmxaAiu0Wiu0Wij9bGOFne-U467C5Qa_XLgKwA9ba4OYOlfhwefFxJ_0Nl5bvww</recordid><startdate>201503</startdate><enddate>201503</enddate><creator>Angelin, Bo</creator><creator>Kristensen, Jens D.</creator><creator>Eriksson, Mats</creator><creator>Carlsson, Bo</creator><creator>Klein, Irwin</creator><creator>Olsson, Anders G.</creator><creator>Chester Ridgway, E.</creator><creator>Ladenson, Paul W.</creator><general>Blackwell Publishing Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>C1K</scope><scope>K9.</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>DG8</scope></search><sort><creationdate>201503</creationdate><title>Reductions in serum levels of LDL cholesterol, apolipoprotein B, triglycerides and lipoprotein(a) in hypercholesterolaemic patients treated with the liver‐selective thyroid hormone receptor agonist eprotirome</title><author>Angelin, Bo ; Kristensen, Jens D. ; Eriksson, Mats ; Carlsson, Bo ; Klein, Irwin ; Olsson, Anders G. ; Chester Ridgway, E. ; Ladenson, Paul W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5891-9906c5f50c2c3c113120fd8e0e786773ee6f0cfaa0994c59cb510f84417f24af3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Anilides - administration & dosage</topic><topic>Anilides - adverse effects</topic><topic>Anticholesteremic Agents - administration & dosage</topic><topic>Anticholesteremic Agents - adverse effects</topic><topic>Apolipoproteins</topic><topic>Apolipoproteins B - drug effects</topic><topic>Blood Pressure - drug effects</topic><topic>Bone and Bones - metabolism</topic><topic>Cholesterol</topic><topic>Cholesterol, LDL - drug effects</topic><topic>Double-Blind Method</topic><topic>Drug Administration Schedule</topic><topic>Dyslipidemia</topic><topic>Female</topic><topic>Heart Rate - drug effects</topic><topic>Humans</topic><topic>hypercholesterolaemia</topic><topic>Hypercholesterolemia - blood</topic><topic>Hypercholesterolemia - drug therapy</topic><topic>Levels</topic><topic>Lipid metabolism</topic><topic>Lipids</topic><topic>lipoprotein</topic><topic>Lipoprotein(a) - blood</topic><topic>Lipoproteins</topic><topic>Liver</topic><topic>Low density lipoprotein</topic><topic>Male</topic><topic>Medicin och hälsovetenskap</topic><topic>Middle Aged</topic><topic>Receptors</topic><topic>Safety measures</topic><topic>Side effects</topic><topic>thyroid</topic><topic>Thyroid gland</topic><topic>Thyrotropin - metabolism</topic><topic>Thyroxine</topic><topic>Triglycerides</topic><topic>Triglycerides - blood</topic><topic>Triiodothyronine - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Angelin, Bo</creatorcontrib><creatorcontrib>Kristensen, Jens D.</creatorcontrib><creatorcontrib>Eriksson, Mats</creatorcontrib><creatorcontrib>Carlsson, Bo</creatorcontrib><creatorcontrib>Klein, Irwin</creatorcontrib><creatorcontrib>Olsson, Anders G.</creatorcontrib><creatorcontrib>Chester Ridgway, E.</creatorcontrib><creatorcontrib>Ladenson, Paul W.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Linköpings universitet</collection><jtitle>Journal of internal medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Angelin, Bo</au><au>Kristensen, Jens D.</au><au>Eriksson, Mats</au><au>Carlsson, Bo</au><au>Klein, Irwin</au><au>Olsson, Anders G.</au><au>Chester Ridgway, E.</au><au>Ladenson, Paul W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reductions in serum levels of LDL cholesterol, apolipoprotein B, triglycerides and lipoprotein(a) in hypercholesterolaemic patients treated with the liver‐selective thyroid hormone receptor agonist eprotirome</atitle><jtitle>Journal of internal medicine</jtitle><addtitle>J Intern Med</addtitle><date>2015-03</date><risdate>2015</risdate><volume>277</volume><issue>3</issue><spage>331</spage><epage>342</epage><pages>331-342</pages><issn>0954-6820</issn><issn>1365-2796</issn><eissn>1365-2796</eissn><abstract>Background
Liver‐selective thyromimetic agents could provide a new approach for treating dyslipidaemia.
Methods
We performed a multicentre, randomized, placebo‐controlled, double‐blind study to evaluate the efficacy and safety of eprotirome, a liver‐selective thyroid hormone receptor agonist, in 98 patients with primary hypercholesterolaemia. After previous drug wash‐out and dietary run‐in, patients received 100 or 200 μg day−1 eprotirome or placebo for 12 weeks. The primary end‐point was change in serum LDL cholesterol; secondary end‐points included changes in other lipid parameters and safety measures.
Results
Eprotirome treatment at 100 and 200 μg daily reduced serum LDL cholesterol levels by 23 ± 5% and 31 ± 4%, respectively, compared with 2 ± 6% for placebo (P < 0.0001). Similar reductions were seen in non‐HDL cholesterol and apolipoprotein (apo) B, whereas serum levels of HDL cholesterol and apo A‐I were unchanged. There were also considerable reductions in serum triglycerides and lipoprotein(a), in particular in patients with elevated levels at baseline. There was no evidence of adverse effects on heart or bone and no changes in serum thyrotropin or triiodothyronine, although the thyroxine level decreased. Low‐grade increases in liver enzymes were evident in most patients.
Conclusion
In hypercholesterolaemic patients, the liver‐selective thyromimetic eprotirome decreased serum levels of atherogenic lipoproteins without signs of extra‐hepatic side effects. Selective stimulation of hepatic thyroid hormone receptors may be an attractive way to modulate lipid metabolism in hyperlipidaemia.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>24754313</pmid><doi>10.1111/joim.12261</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of internal medicine, 2015-03, Vol.277 (3), p.331-342 |
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| source | Wiley Online Library website; MEDLINE; Free E-Journal (出版社公開部分のみ）; Wiley Blackwell Journals |
| subjects | Anilides - administration & dosage Anilides - adverse effects Anticholesteremic Agents - administration & dosage Anticholesteremic Agents - adverse effects Apolipoproteins Apolipoproteins B - drug effects Blood Pressure - drug effects Bone and Bones - metabolism Cholesterol Cholesterol, LDL - drug effects Double-Blind Method Drug Administration Schedule Dyslipidemia Female Heart Rate - drug effects Humans hypercholesterolaemia Hypercholesterolemia - blood Hypercholesterolemia - drug therapy Levels Lipid metabolism Lipids lipoprotein Lipoprotein(a) - blood Lipoproteins Liver Low density lipoprotein Male Medicin och hälsovetenskap Middle Aged Receptors Safety measures Side effects thyroid Thyroid gland Thyrotropin - metabolism Thyroxine Triglycerides Triglycerides - blood Triiodothyronine - metabolism |
| title | Reductions in serum levels of LDL cholesterol, apolipoprotein B, triglycerides and lipoprotein(a) in hypercholesterolaemic patients treated with the liver‐selective thyroid hormone receptor agonist eprotirome |
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