Effect of Evolocumab on Lipoprotein Particles
The level of low-density lipoprotein cholesterol (LDL-C) reflects the cholesterol carried mainly by low-density lipoprotein particles (LDL-P). LDL-C, however, does not always correlate with LDL-P because of the variable amounts of cholesterol per particle. Consideration of LDL-P concentrations in ad...
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| Veröffentlicht in: | The American journal of cardiology 2018-02, Vol.121 (3), p.308-314 |
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| creator | Toth, Peter P. Sattar, Naveed Blom, Dirk J. Martin, Seth S. Jones, Steven R. Monsalvo, Maria Laura Elliott, Mary Davis, Mike Somaratne, Ransi Preiss, David |
| description | The level of low-density lipoprotein cholesterol (LDL-C) reflects the cholesterol carried mainly by low-density lipoprotein particles (LDL-P). LDL-C, however, does not always correlate with LDL-P because of the variable amounts of cholesterol per particle. Consideration of LDL-P concentrations in addition to LDL-C may help guide therapeutic decisions in a select number of patients. Evolocumab is a fully human monoclonal antibody directed against proprotein convertase subtilisin-kexin type 9 that lowers both LDL-C and cardiovascular events. To evaluate the effect of evolocumab on serum levels and size of lipoprotein particles, we conducted a post hoc subanalysis of 619 patients from the Durable Effect of PCSK9 Antibody Compared with Placebo Study or DESCARTES trial, a 52-week, randomized, double-blind, placebo-controlled, global study of patients with hyperlipidemia. At baseline, mean LDL-P concentration was 1077 nmol/L for the placebo group and 1100 nmol/L for the evolocumab group. In patients receiving evolocumab, week 52 total LDL-P concentration decreased to 610 nmol/L, a treatment difference of 50% versus placebo. Evolocumab also reduced concentrations of medium very low-density lipoprotein particles (VLDL-P), small VLDL-P, and intermediate-density lipoprotein particle: median (Q1, Q3) changes were −15.2% (−48, 48), −29% (−54, 18), and −36% (−70, 22), respectively. Mean (95% confidence interval) % changes in total LDL particle size in the evolocumab group was −1.7 (−2.0, −1.4); % changes in HDL and VLDL particle sizes were 1.1 (0.7, 1.5) and 8.7 (7.0, 10.5), respectively. Changes in total LDL, HDL, and VLDL particle sizes (vs placebo) were all significant (p |
| doi_str_mv | 10.1016/j.amjcard.2017.10.028 |
| format | Article |
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LDL-C, however, does not always correlate with LDL-P because of the variable amounts of cholesterol per particle. Consideration of LDL-P concentrations in addition to LDL-C may help guide therapeutic decisions in a select number of patients. Evolocumab is a fully human monoclonal antibody directed against proprotein convertase subtilisin-kexin type 9 that lowers both LDL-C and cardiovascular events. To evaluate the effect of evolocumab on serum levels and size of lipoprotein particles, we conducted a post hoc subanalysis of 619 patients from the Durable Effect of PCSK9 Antibody Compared with Placebo Study or DESCARTES trial, a 52-week, randomized, double-blind, placebo-controlled, global study of patients with hyperlipidemia. At baseline, mean LDL-P concentration was 1077 nmol/L for the placebo group and 1100 nmol/L for the evolocumab group. In patients receiving evolocumab, week 52 total LDL-P concentration decreased to 610 nmol/L, a treatment difference of 50% versus placebo. Evolocumab also reduced concentrations of medium very low-density lipoprotein particles (VLDL-P), small VLDL-P, and intermediate-density lipoprotein particle: median (Q1, Q3) changes were −15.2% (−48, 48), −29% (−54, 18), and −36% (−70, 22), respectively. Mean (95% confidence interval) % changes in total LDL particle size in the evolocumab group was −1.7 (−2.0, −1.4); % changes in HDL and VLDL particle sizes were 1.1 (0.7, 1.5) and 8.7 (7.0, 10.5), respectively. Changes in total LDL, HDL, and VLDL particle sizes (vs placebo) were all significant (p <0.001). In conclusion, evolocumab significantly lowers atherogenic lipoprotein particles including low-density and remnant lipoproteins.</description><identifier>ISSN: 0002-9149</identifier><identifier>EISSN: 1879-1913</identifier><identifier>DOI: 10.1016/j.amjcard.2017.10.028</identifier><identifier>PMID: 29221604</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adults ; Cardiovascular disease ; Cholesterol ; Confidence intervals ; Density ; Descartes ; Diabetes ; High density lipoprotein ; Hyperlipidemia ; Kexin ; Lipids ; Lipoproteins ; Lipoproteins (very low density) ; Low density lipoprotein ; Monoclonal antibodies ; NMR ; Nuclear magnetic resonance ; Patients ; Proprotein convertases ; Serum levels ; Spectrum analysis ; Statins ; Subtilisin ; Triglycerides</subject><ispartof>The American journal of cardiology, 2018-02, Vol.121 (3), p.308-314</ispartof><rights>2017 Elsevier Inc.</rights><rights>Copyright © 2017 Elsevier Inc. All rights reserved.</rights><rights>2017. Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c506t-9c04a089035de62556a5c102e2fa29d9756cae0e96dd873ab0e066e99123b5553</citedby><cites>FETCH-LOGICAL-c506t-9c04a089035de62556a5c102e2fa29d9756cae0e96dd873ab0e066e99123b5553</cites><orcidid>0000-0001-5810-5460 ; 0000-0003-3139-1836 ; 0000-0003-3965-5912</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0002914917316855$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29221604$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Toth, Peter P.</creatorcontrib><creatorcontrib>Sattar, Naveed</creatorcontrib><creatorcontrib>Blom, Dirk J.</creatorcontrib><creatorcontrib>Martin, Seth S.</creatorcontrib><creatorcontrib>Jones, Steven R.</creatorcontrib><creatorcontrib>Monsalvo, Maria Laura</creatorcontrib><creatorcontrib>Elliott, Mary</creatorcontrib><creatorcontrib>Davis, Mike</creatorcontrib><creatorcontrib>Somaratne, Ransi</creatorcontrib><creatorcontrib>Preiss, David</creatorcontrib><title>Effect of Evolocumab on Lipoprotein Particles</title><title>The American journal of cardiology</title><addtitle>Am J Cardiol</addtitle><description>The level of low-density lipoprotein cholesterol (LDL-C) reflects the cholesterol carried mainly by low-density lipoprotein particles (LDL-P). LDL-C, however, does not always correlate with LDL-P because of the variable amounts of cholesterol per particle. Consideration of LDL-P concentrations in addition to LDL-C may help guide therapeutic decisions in a select number of patients. Evolocumab is a fully human monoclonal antibody directed against proprotein convertase subtilisin-kexin type 9 that lowers both LDL-C and cardiovascular events. To evaluate the effect of evolocumab on serum levels and size of lipoprotein particles, we conducted a post hoc subanalysis of 619 patients from the Durable Effect of PCSK9 Antibody Compared with Placebo Study or DESCARTES trial, a 52-week, randomized, double-blind, placebo-controlled, global study of patients with hyperlipidemia. At baseline, mean LDL-P concentration was 1077 nmol/L for the placebo group and 1100 nmol/L for the evolocumab group. In patients receiving evolocumab, week 52 total LDL-P concentration decreased to 610 nmol/L, a treatment difference of 50% versus placebo. Evolocumab also reduced concentrations of medium very low-density lipoprotein particles (VLDL-P), small VLDL-P, and intermediate-density lipoprotein particle: median (Q1, Q3) changes were −15.2% (−48, 48), −29% (−54, 18), and −36% (−70, 22), respectively. Mean (95% confidence interval) % changes in total LDL particle size in the evolocumab group was −1.7 (−2.0, −1.4); % changes in HDL and VLDL particle sizes were 1.1 (0.7, 1.5) and 8.7 (7.0, 10.5), respectively. Changes in total LDL, HDL, and VLDL particle sizes (vs placebo) were all significant (p <0.001). 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Cardiol</addtitle><date>2018-02-01</date><risdate>2018</risdate><volume>121</volume><issue>3</issue><spage>308</spage><epage>314</epage><pages>308-314</pages><issn>0002-9149</issn><eissn>1879-1913</eissn><abstract>The level of low-density lipoprotein cholesterol (LDL-C) reflects the cholesterol carried mainly by low-density lipoprotein particles (LDL-P). LDL-C, however, does not always correlate with LDL-P because of the variable amounts of cholesterol per particle. Consideration of LDL-P concentrations in addition to LDL-C may help guide therapeutic decisions in a select number of patients. Evolocumab is a fully human monoclonal antibody directed against proprotein convertase subtilisin-kexin type 9 that lowers both LDL-C and cardiovascular events. To evaluate the effect of evolocumab on serum levels and size of lipoprotein particles, we conducted a post hoc subanalysis of 619 patients from the Durable Effect of PCSK9 Antibody Compared with Placebo Study or DESCARTES trial, a 52-week, randomized, double-blind, placebo-controlled, global study of patients with hyperlipidemia. At baseline, mean LDL-P concentration was 1077 nmol/L for the placebo group and 1100 nmol/L for the evolocumab group. In patients receiving evolocumab, week 52 total LDL-P concentration decreased to 610 nmol/L, a treatment difference of 50% versus placebo. Evolocumab also reduced concentrations of medium very low-density lipoprotein particles (VLDL-P), small VLDL-P, and intermediate-density lipoprotein particle: median (Q1, Q3) changes were −15.2% (−48, 48), −29% (−54, 18), and −36% (−70, 22), respectively. Mean (95% confidence interval) % changes in total LDL particle size in the evolocumab group was −1.7 (−2.0, −1.4); % changes in HDL and VLDL particle sizes were 1.1 (0.7, 1.5) and 8.7 (7.0, 10.5), respectively. Changes in total LDL, HDL, and VLDL particle sizes (vs placebo) were all significant (p <0.001). 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| ispartof | The American journal of cardiology, 2018-02, Vol.121 (3), p.308-314 |
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| source | Elsevier ScienceDirect Journals |
| subjects | Adults Cardiovascular disease Cholesterol Confidence intervals Density Descartes Diabetes High density lipoprotein Hyperlipidemia Kexin Lipids Lipoproteins Lipoproteins (very low density) Low density lipoprotein Monoclonal antibodies NMR Nuclear magnetic resonance Patients Proprotein convertases Serum levels Spectrum analysis Statins Subtilisin Triglycerides |
| title | Effect of Evolocumab on Lipoprotein Particles |
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