TY - JOUR
T1 - Effect of Evolocumab on Lipoprotein Particles
AU - Toth, Peter P.
AU - Sattar, Naveed
AU - Blom, Dirk J.
AU - Martin, Seth S.
AU - Jones, Steven R.
AU - Monsalvo, Maria Laura
AU - Elliott, Mary
AU - Davis, Mike
AU - Somaratne, Ransi
AU - Preiss, David
N1 - Funding Information:
Funding: This study was funded by Amgen Inc .
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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). In conclusion, evolocumab significantly lowers atherogenic lipoprotein particles including low-density and remnant lipoproteins.
AB - 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). In conclusion, evolocumab significantly lowers atherogenic lipoprotein particles including low-density and remnant lipoproteins.
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U2 - 10.1016/j.amjcard.2017.10.028
DO - 10.1016/j.amjcard.2017.10.028
M3 - Article
C2 - 29221604
AN - SCOPUS:85037060506
SN - 0002-9149
VL - 121
SP - 308
EP - 314
JO - American Journal of Cardiology
JF - American Journal of Cardiology
IS - 3
ER -