AMG145, a Monoclonal Antibody Against Proprotein Convertase Subtilisin Kexin Type 9, Significantly Reduces Lipoprotein(a) in Hypercholesterolemic Patients Receiving Statin Therapy: An Analysis From the LDL-C Assessment With Proprotein Convertase Subtilisin Kexin Type 9 Monoclonal Antibody Inhibition Combined With Statin Therapy (LAPLACE)–Thrombolysis in Myocardial Infarction (TIMI) 57 Trial
BACKGROUND—Lipoprotein(a) [Lp(a)] is an emerging risk factor for cardiovascular disease. Currently, there are few available therapies to lower Lp(a). We sought to evaluate the impact of AMG145, a monoclonal antibody against proprotein convertase subtilisin kexin type 9 (PCSK9), on Lp(a). METHODS AND...
Gespeichert in:
| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 2013-08, Vol.128 (9), p.962-969 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 969 |
|---|---|
| container_issue | 9 |
| container_start_page | 962 |
| container_title | Circulation (New York, N.Y.) |
| container_volume | 128 |
| creator | Desai, Nihar R. Kohli, Payal Giugliano, Robert P. O’Donoghue, Michelle L. Somaratne, Ransi Zhou, Jing Hoffman, Elaine B. Huang, Fannie Rogers, William J. Wasserman, Scott M. Scott, Robert Sabatine, Marc S. |
| description | BACKGROUND—Lipoprotein(a) [Lp(a)] is an emerging risk factor for cardiovascular disease. Currently, there are few available therapies to lower Lp(a). We sought to evaluate the impact of AMG145, a monoclonal antibody against proprotein convertase subtilisin kexin type 9 (PCSK9), on Lp(a).
METHODS AND RESULTS—As part of the LDL-C Assessment With PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy (LAPLACE)–Thrombolysis in Myocardial Infarction (TIMI) 57 trial, 631 patients with hypercholesterolemia receiving statin therapy were randomized to receive AMG145 at 1 of 3 different doses every 2 weeks or 1 of 3 different doses every 4 weeks versus placebo. Lp(a) and other lipid parameters were measured at baseline and at week 12. Compared with placebo, AMG145 70 mg, 105 mg, and 140 mg every 2 weeks reduced Lp(a) at 12 weeks by 18%, 32%, and 32%, respectively (P |
| doi_str_mv | 10.1161/CIRCULATIONAHA.113.001969 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1428519530</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1428519530</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3459-dfb707d1c868674817cf8d173928a0cad2057e80570f9778526eeedb55a27a3b3</originalsourceid><addsrcrecordid>eNqVks1u1DAUhQMCQSm8AjILpKnUKXYcxwkSiyj0JyJDq3YqlpHjOI3BsQfb05Ide5a8IU-Cy7SgSixAsmz5-rvHR1cnil4guIdQil6V1Wl5XhfL6vh9cVSEGt6DEOVpfj_aQiRO5gnB-YNoC0KYzymO48fRE-c-hmuKKXkUPY5xliWY4K1734rFIUrILmBgYbThymimQKG9bE03geKCSe08OLFmZY0XUoPS6EthPXMCnK1bL5V0ofpOfAn7cloJkO-CM3mhZS85015N4FR0ay4cqOXqVmXGdkDgjwJv-WCUcF7YcIySgxPmpdDehT4u5KXUF-DMh1qQH4Rlq-l18BcWU5OTDhxYMwI_CFC_reclKJwTzo1BAHyQfvg_53-dQaUH2UovzbXC2Eotuo30XVdgVhcndVHu7_z4-n05BFet2TgMzGIynNlOBt1K98zyX3KzZbWodgChYGnD09PoYc-UE89uzu3o_GB_WR7N6-PDqizqOccJyedd31JIO8SzNEtpkiHK-6xDFOdxxiBnXQwJFVnYYJ9TmpE4FUJ0LSEspgy3eDuabXTDYD6vw-ibUToulGJamLVrUBJnBOUEw4DmG5Rb45wVfbOycmR2ahBsrrPY3M1iqOFmk8XQ-_zmm3U7iu535234AvDyBmCOM9Vbprl0fziaUkhQFrg3G-7KqBAT90mtr4RtBsGUH_7ByE9SQwQU</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1428519530</pqid></control><display><type>article</type><title>AMG145, a Monoclonal Antibody Against Proprotein Convertase Subtilisin Kexin Type 9, Significantly Reduces Lipoprotein(a) in Hypercholesterolemic Patients Receiving Statin Therapy: An Analysis From the LDL-C Assessment With Proprotein Convertase Subtilisin Kexin Type 9 Monoclonal Antibody Inhibition Combined With Statin Therapy (LAPLACE)–Thrombolysis in Myocardial Infarction (TIMI) 57 Trial</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>American Heart Association</source><source>Journals@Ovid Complete</source><creator>Desai, Nihar R. ; Kohli, Payal ; Giugliano, Robert P. ; O’Donoghue, Michelle L. ; Somaratne, Ransi ; Zhou, Jing ; Hoffman, Elaine B. ; Huang, Fannie ; Rogers, William J. ; Wasserman, Scott M. ; Scott, Robert ; Sabatine, Marc S.</creator><creatorcontrib>Desai, Nihar R. ; Kohli, Payal ; Giugliano, Robert P. ; O’Donoghue, Michelle L. ; Somaratne, Ransi ; Zhou, Jing ; Hoffman, Elaine B. ; Huang, Fannie ; Rogers, William J. ; Wasserman, Scott M. ; Scott, Robert ; Sabatine, Marc S.</creatorcontrib><description>BACKGROUND—Lipoprotein(a) [Lp(a)] is an emerging risk factor for cardiovascular disease. Currently, there are few available therapies to lower Lp(a). We sought to evaluate the impact of AMG145, a monoclonal antibody against proprotein convertase subtilisin kexin type 9 (PCSK9), on Lp(a).
METHODS AND RESULTS—As part of the LDL-C Assessment With PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy (LAPLACE)–Thrombolysis in Myocardial Infarction (TIMI) 57 trial, 631 patients with hypercholesterolemia receiving statin therapy were randomized to receive AMG145 at 1 of 3 different doses every 2 weeks or 1 of 3 different doses every 4 weeks versus placebo. Lp(a) and other lipid parameters were measured at baseline and at week 12. Compared with placebo, AMG145 70 mg, 105 mg, and 140 mg every 2 weeks reduced Lp(a) at 12 weeks by 18%, 32%, and 32%, respectively (P<0.001 for each dose versus placebo). Likewise, AMG145 280 mg, 350 mg, and 420 mg every 4 weeks reduced Lp(a) by 18%, 23%, and 23%, respectively (P<0.001 for each dose versus placebo). The reduction in Lp(a) correlated with the reduction in low-density lipoprotein cholesterol (ρ=0.33, P<0.001). The effect of AMG145 on Lp(a) was consistent regardless of age, sex, race, history of diabetes mellitus, and background statin regimen. Patients with higher levels of Lp(a) at baseline had larger absolute reductions but comparatively smaller percent reductions in Lp(a) with AMG145 compared with those with lower baseline Lp(a) values.
CONCLUSIONS—AMG145 significantly reduces Lp(a), by up to 32%, among subjects with hypercholesterolemia receiving statin therapy, offering an additional, complementary benefit beyond robust low-density lipoprotein cholesterol reduction with regard to a patient’s atherogenic lipid profile.
CLINICAL TRIAL REGISTRATION—URLhttp://www.clinicaltrials.gov. Unique identifierNCT01380730.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/CIRCULATIONAHA.113.001969</identifier><identifier>PMID: 23884353</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: by the American College of Cardiology Foundation and the American Heart Association, Inc</publisher><subject>Aged ; Antibodies, Monoclonal - therapeutic use ; Biological and medical sciences ; Biomarkers - blood ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Cholesterol, LDL - blood ; Coronary heart disease ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Disorders of blood lipids. Hyperlipoproteinemia ; Dose-Response Relationship, Drug ; Double-Blind Method ; Drug Therapy, Combination ; Female ; Heart ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use ; Hypercholesterolemia - blood ; Hypercholesterolemia - drug therapy ; Lipoprotein(a) - blood ; Logistic Models ; Male ; Medical sciences ; Metabolic diseases ; Middle Aged ; Myocardial Infarction - drug therapy ; Myocarditis. Cardiomyopathies ; Proprotein Convertase 9 ; Proprotein Convertases - immunology ; Risk Factors ; Serine Endopeptidases - immunology ; Thrombolytic Therapy</subject><ispartof>Circulation (New York, N.Y.), 2013-08, Vol.128 (9), p.962-969</ispartof><rights>2013 by the American College of Cardiology Foundation and the American Heart Association, Inc.</rights><rights>2014 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3459-dfb707d1c868674817cf8d173928a0cad2057e80570f9778526eeedb55a27a3b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3687,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27670518$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23884353$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Desai, Nihar R.</creatorcontrib><creatorcontrib>Kohli, Payal</creatorcontrib><creatorcontrib>Giugliano, Robert P.</creatorcontrib><creatorcontrib>O’Donoghue, Michelle L.</creatorcontrib><creatorcontrib>Somaratne, Ransi</creatorcontrib><creatorcontrib>Zhou, Jing</creatorcontrib><creatorcontrib>Hoffman, Elaine B.</creatorcontrib><creatorcontrib>Huang, Fannie</creatorcontrib><creatorcontrib>Rogers, William J.</creatorcontrib><creatorcontrib>Wasserman, Scott M.</creatorcontrib><creatorcontrib>Scott, Robert</creatorcontrib><creatorcontrib>Sabatine, Marc S.</creatorcontrib><title>AMG145, a Monoclonal Antibody Against Proprotein Convertase Subtilisin Kexin Type 9, Significantly Reduces Lipoprotein(a) in Hypercholesterolemic Patients Receiving Statin Therapy: An Analysis From the LDL-C Assessment With Proprotein Convertase Subtilisin Kexin Type 9 Monoclonal Antibody Inhibition Combined With Statin Therapy (LAPLACE)–Thrombolysis in Myocardial Infarction (TIMI) 57 Trial</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>BACKGROUND—Lipoprotein(a) [Lp(a)] is an emerging risk factor for cardiovascular disease. Currently, there are few available therapies to lower Lp(a). We sought to evaluate the impact of AMG145, a monoclonal antibody against proprotein convertase subtilisin kexin type 9 (PCSK9), on Lp(a).
METHODS AND RESULTS—As part of the LDL-C Assessment With PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy (LAPLACE)–Thrombolysis in Myocardial Infarction (TIMI) 57 trial, 631 patients with hypercholesterolemia receiving statin therapy were randomized to receive AMG145 at 1 of 3 different doses every 2 weeks or 1 of 3 different doses every 4 weeks versus placebo. Lp(a) and other lipid parameters were measured at baseline and at week 12. Compared with placebo, AMG145 70 mg, 105 mg, and 140 mg every 2 weeks reduced Lp(a) at 12 weeks by 18%, 32%, and 32%, respectively (P<0.001 for each dose versus placebo). Likewise, AMG145 280 mg, 350 mg, and 420 mg every 4 weeks reduced Lp(a) by 18%, 23%, and 23%, respectively (P<0.001 for each dose versus placebo). The reduction in Lp(a) correlated with the reduction in low-density lipoprotein cholesterol (ρ=0.33, P<0.001). The effect of AMG145 on Lp(a) was consistent regardless of age, sex, race, history of diabetes mellitus, and background statin regimen. Patients with higher levels of Lp(a) at baseline had larger absolute reductions but comparatively smaller percent reductions in Lp(a) with AMG145 compared with those with lower baseline Lp(a) values.
CONCLUSIONS—AMG145 significantly reduces Lp(a), by up to 32%, among subjects with hypercholesterolemia receiving statin therapy, offering an additional, complementary benefit beyond robust low-density lipoprotein cholesterol reduction with regard to a patient’s atherogenic lipid profile.
CLINICAL TRIAL REGISTRATION—URLhttp://www.clinicaltrials.gov. Unique identifierNCT01380730.</description><subject>Aged</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - blood</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Cholesterol, LDL - blood</subject><subject>Coronary heart disease</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Disorders of blood lipids. Hyperlipoproteinemia</subject><subject>Dose-Response Relationship, Drug</subject><subject>Double-Blind Method</subject><subject>Drug Therapy, Combination</subject><subject>Female</subject><subject>Heart</subject><subject>Humans</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use</subject><subject>Hypercholesterolemia - blood</subject><subject>Hypercholesterolemia - drug therapy</subject><subject>Lipoprotein(a) - blood</subject><subject>Logistic Models</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metabolic diseases</subject><subject>Middle Aged</subject><subject>Myocardial Infarction - drug therapy</subject><subject>Myocarditis. Cardiomyopathies</subject><subject>Proprotein Convertase 9</subject><subject>Proprotein Convertases - immunology</subject><subject>Risk Factors</subject><subject>Serine Endopeptidases - immunology</subject><subject>Thrombolytic Therapy</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVks1u1DAUhQMCQSm8AjILpKnUKXYcxwkSiyj0JyJDq3YqlpHjOI3BsQfb05Ide5a8IU-Cy7SgSixAsmz5-rvHR1cnil4guIdQil6V1Wl5XhfL6vh9cVSEGt6DEOVpfj_aQiRO5gnB-YNoC0KYzymO48fRE-c-hmuKKXkUPY5xliWY4K1734rFIUrILmBgYbThymimQKG9bE03geKCSe08OLFmZY0XUoPS6EthPXMCnK1bL5V0ofpOfAn7cloJkO-CM3mhZS85015N4FR0ay4cqOXqVmXGdkDgjwJv-WCUcF7YcIySgxPmpdDehT4u5KXUF-DMh1qQH4Rlq-l18BcWU5OTDhxYMwI_CFC_reclKJwTzo1BAHyQfvg_53-dQaUH2UovzbXC2Eotuo30XVdgVhcndVHu7_z4-n05BFet2TgMzGIynNlOBt1K98zyX3KzZbWodgChYGnD09PoYc-UE89uzu3o_GB_WR7N6-PDqizqOccJyedd31JIO8SzNEtpkiHK-6xDFOdxxiBnXQwJFVnYYJ9TmpE4FUJ0LSEspgy3eDuabXTDYD6vw-ibUToulGJamLVrUBJnBOUEw4DmG5Rb45wVfbOycmR2ahBsrrPY3M1iqOFmk8XQ-_zmm3U7iu535234AvDyBmCOM9Vbprl0fziaUkhQFrg3G-7KqBAT90mtr4RtBsGUH_7ByE9SQwQU</recordid><startdate>20130827</startdate><enddate>20130827</enddate><creator>Desai, Nihar R.</creator><creator>Kohli, Payal</creator><creator>Giugliano, Robert P.</creator><creator>O’Donoghue, Michelle L.</creator><creator>Somaratne, Ransi</creator><creator>Zhou, Jing</creator><creator>Hoffman, Elaine B.</creator><creator>Huang, Fannie</creator><creator>Rogers, William J.</creator><creator>Wasserman, Scott M.</creator><creator>Scott, Robert</creator><creator>Sabatine, Marc S.</creator><general>by the American College of Cardiology Foundation and the American Heart Association, Inc</general><general>Lippincott Williams & Wilkins</general><scope>IQODW</scope><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>7X8</scope></search><sort><creationdate>20130827</creationdate><title>AMG145, a Monoclonal Antibody Against Proprotein Convertase Subtilisin Kexin Type 9, Significantly Reduces Lipoprotein(a) in Hypercholesterolemic Patients Receiving Statin Therapy: An Analysis From the LDL-C Assessment With Proprotein Convertase Subtilisin Kexin Type 9 Monoclonal Antibody Inhibition Combined With Statin Therapy (LAPLACE)–Thrombolysis in Myocardial Infarction (TIMI) 57 Trial</title><author>Desai, Nihar R. ; Kohli, Payal ; Giugliano, Robert P. ; O’Donoghue, Michelle L. ; Somaratne, Ransi ; Zhou, Jing ; Hoffman, Elaine B. ; Huang, Fannie ; Rogers, William J. ; Wasserman, Scott M. ; Scott, Robert ; Sabatine, Marc S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3459-dfb707d1c868674817cf8d173928a0cad2057e80570f9778526eeedb55a27a3b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Aged</topic><topic>Antibodies, Monoclonal - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - blood</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Cholesterol, LDL - blood</topic><topic>Coronary heart disease</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</topic><topic>Disorders of blood lipids. Hyperlipoproteinemia</topic><topic>Dose-Response Relationship, Drug</topic><topic>Double-Blind Method</topic><topic>Drug Therapy, Combination</topic><topic>Female</topic><topic>Heart</topic><topic>Humans</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use</topic><topic>Hypercholesterolemia - blood</topic><topic>Hypercholesterolemia - drug therapy</topic><topic>Lipoprotein(a) - blood</topic><topic>Logistic Models</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metabolic diseases</topic><topic>Middle Aged</topic><topic>Myocardial Infarction - drug therapy</topic><topic>Myocarditis. Cardiomyopathies</topic><topic>Proprotein Convertase 9</topic><topic>Proprotein Convertases - immunology</topic><topic>Risk Factors</topic><topic>Serine Endopeptidases - immunology</topic><topic>Thrombolytic Therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Desai, Nihar R.</creatorcontrib><creatorcontrib>Kohli, Payal</creatorcontrib><creatorcontrib>Giugliano, Robert P.</creatorcontrib><creatorcontrib>O’Donoghue, Michelle L.</creatorcontrib><creatorcontrib>Somaratne, Ransi</creatorcontrib><creatorcontrib>Zhou, Jing</creatorcontrib><creatorcontrib>Hoffman, Elaine B.</creatorcontrib><creatorcontrib>Huang, Fannie</creatorcontrib><creatorcontrib>Rogers, William J.</creatorcontrib><creatorcontrib>Wasserman, Scott M.</creatorcontrib><creatorcontrib>Scott, Robert</creatorcontrib><creatorcontrib>Sabatine, Marc S.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Desai, Nihar R.</au><au>Kohli, Payal</au><au>Giugliano, Robert P.</au><au>O’Donoghue, Michelle L.</au><au>Somaratne, Ransi</au><au>Zhou, Jing</au><au>Hoffman, Elaine B.</au><au>Huang, Fannie</au><au>Rogers, William J.</au><au>Wasserman, Scott M.</au><au>Scott, Robert</au><au>Sabatine, Marc S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>AMG145, a Monoclonal Antibody Against Proprotein Convertase Subtilisin Kexin Type 9, Significantly Reduces Lipoprotein(a) in Hypercholesterolemic Patients Receiving Statin Therapy: An Analysis From the LDL-C Assessment With Proprotein Convertase Subtilisin Kexin Type 9 Monoclonal Antibody Inhibition Combined With Statin Therapy (LAPLACE)–Thrombolysis in Myocardial Infarction (TIMI) 57 Trial</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2013-08-27</date><risdate>2013</risdate><volume>128</volume><issue>9</issue><spage>962</spage><epage>969</epage><pages>962-969</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>BACKGROUND—Lipoprotein(a) [Lp(a)] is an emerging risk factor for cardiovascular disease. Currently, there are few available therapies to lower Lp(a). We sought to evaluate the impact of AMG145, a monoclonal antibody against proprotein convertase subtilisin kexin type 9 (PCSK9), on Lp(a).
METHODS AND RESULTS—As part of the LDL-C Assessment With PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy (LAPLACE)–Thrombolysis in Myocardial Infarction (TIMI) 57 trial, 631 patients with hypercholesterolemia receiving statin therapy were randomized to receive AMG145 at 1 of 3 different doses every 2 weeks or 1 of 3 different doses every 4 weeks versus placebo. Lp(a) and other lipid parameters were measured at baseline and at week 12. Compared with placebo, AMG145 70 mg, 105 mg, and 140 mg every 2 weeks reduced Lp(a) at 12 weeks by 18%, 32%, and 32%, respectively (P<0.001 for each dose versus placebo). Likewise, AMG145 280 mg, 350 mg, and 420 mg every 4 weeks reduced Lp(a) by 18%, 23%, and 23%, respectively (P<0.001 for each dose versus placebo). The reduction in Lp(a) correlated with the reduction in low-density lipoprotein cholesterol (ρ=0.33, P<0.001). The effect of AMG145 on Lp(a) was consistent regardless of age, sex, race, history of diabetes mellitus, and background statin regimen. Patients with higher levels of Lp(a) at baseline had larger absolute reductions but comparatively smaller percent reductions in Lp(a) with AMG145 compared with those with lower baseline Lp(a) values.
CONCLUSIONS—AMG145 significantly reduces Lp(a), by up to 32%, among subjects with hypercholesterolemia receiving statin therapy, offering an additional, complementary benefit beyond robust low-density lipoprotein cholesterol reduction with regard to a patient’s atherogenic lipid profile.
CLINICAL TRIAL REGISTRATION—URLhttp://www.clinicaltrials.gov. Unique identifierNCT01380730.</abstract><cop>Hagerstown, MD</cop><pub>by the American College of Cardiology Foundation and the American Heart Association, Inc</pub><pmid>23884353</pmid><doi>10.1161/CIRCULATIONAHA.113.001969</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0009-7322 |
| ispartof | Circulation (New York, N.Y.), 2013-08, Vol.128 (9), p.962-969 |
| issn | 0009-7322 1524-4539 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1428519530 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; American Heart Association; Journals@Ovid Complete |
| subjects | Aged Antibodies, Monoclonal - therapeutic use Biological and medical sciences Biomarkers - blood Blood and lymphatic vessels Cardiology. Vascular system Cholesterol, LDL - blood Coronary heart disease Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Disorders of blood lipids. Hyperlipoproteinemia Dose-Response Relationship, Drug Double-Blind Method Drug Therapy, Combination Female Heart Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use Hypercholesterolemia - blood Hypercholesterolemia - drug therapy Lipoprotein(a) - blood Logistic Models Male Medical sciences Metabolic diseases Middle Aged Myocardial Infarction - drug therapy Myocarditis. Cardiomyopathies Proprotein Convertase 9 Proprotein Convertases - immunology Risk Factors Serine Endopeptidases - immunology Thrombolytic Therapy |
| title | AMG145, a Monoclonal Antibody Against Proprotein Convertase Subtilisin Kexin Type 9, Significantly Reduces Lipoprotein(a) in Hypercholesterolemic Patients Receiving Statin Therapy: An Analysis From the LDL-C Assessment With Proprotein Convertase Subtilisin Kexin Type 9 Monoclonal Antibody Inhibition Combined With Statin Therapy (LAPLACE)–Thrombolysis in Myocardial Infarction (TIMI) 57 Trial |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T16%3A44%3A54IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=AMG145,%20a%20Monoclonal%20Antibody%20Against%20Proprotein%20Convertase%20Subtilisin%20Kexin%20Type%209,%20Significantly%20Reduces%20Lipoprotein(a)%20in%20Hypercholesterolemic%20Patients%20Receiving%20Statin%20Therapy:%20An%20Analysis%20From%20the%20LDL-C%20Assessment%20With%20Proprotein%20Convertase%20Subtilisin%20Kexin%20Type%209%20Monoclonal%20Antibody%20Inhibition%20Combined%20With%20Statin%20Therapy%20(LAPLACE)%E2%80%93Thrombolysis%20in%20Myocardial%20Infarction%20(TIMI)%2057%20Trial&rft.jtitle=Circulation%20(New%20York,%20N.Y.)&rft.au=Desai,%20Nihar%20R.&rft.date=2013-08-27&rft.volume=128&rft.issue=9&rft.spage=962&rft.epage=969&rft.pages=962-969&rft.issn=0009-7322&rft.eissn=1524-4539&rft.coden=CIRCAZ&rft_id=info:doi/10.1161/CIRCULATIONAHA.113.001969&rft_dat=%3Cproquest_cross%3E1428519530%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1428519530&rft_id=info:pmid/23884353&rfr_iscdi=true |