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Stiekema, Lotte C A; Stroes, Erik S G; Verweij, Simone L; Kassahun, Helina; Chen, Lisa; Wasserman, Scott M; Sabatine, Marc S; Mani, Venkatesh; Fayad, Zahi A
European heart journal, 09/2019, Letnik: 40, Številka: 33Journal Article
Abstract Aims Subjects with lipoprotein(a) Lp(a) elevation have increased arterial wall inflammation and cardiovascular risk. In patients at increased cardiovascular risk, arterial wall inflammation is reduced following lipid-lowering therapy by statin treatment or lipoprotein apheresis. However, it is unknown whether lipid-lowering treatment in elevated Lp(a) subjects alters arterial wall inflammation. We evaluated whether evolocumab, which lowers both low-density lipoprotein cholesterol (LDL-C) and Lp(a), attenuates arterial wall inflammation in patients with elevated Lp(a). Methods and results In this multicentre, randomized, double-blind, placebo-controlled study, 129 patients {median interquartile range (IQR): age 60.0 54.0–67.0 years, Lp(a) 200.0 155.5–301.5 nmol/L 80.0 (62.5–121.0) mg/dL; mean standard deviation (SD) LDL-C 3.7 1.0 mmol/L 144.0 (39.7) mg/dL; National Cholesterol Education Program high risk, 25.6%} were randomized to monthly subcutaneous evolocumab 420 mg or placebo. Compared with placebo, evolocumab reduced LDL-C by 60.7% 95% confidence interval (CI) 65.8–55.5 and Lp(a) by 13.9% (95% CI 19.3–8.5). Among evolocumab-treated patients, the Week 16 mean (SD) LDL-C level was 1.6 (0.7) mmol/L 60.1 (28.1) mg/dL, and the median (IQR) Lp(a) level was 188.0 (140.0–268.0) nmol/L 75.2 (56.0–107.2) mg/dL. Arterial wall inflammation most diseased segment target-to-background ratio (MDS TBR) in the index vessel (left carotid, right carotid, or thoracic aorta) was assessed by 18F-fluoro-deoxyglucose positron-emission tomography/computed tomography. Week 16 index vessel MDS TBR was not significantly altered with evolocumab (−8.3%) vs. placebo (−5.3%) treatment difference −3.0% (95% CI −7.4% to 1.4%); P = 0.18. Conclusion Evolocumab treatment in patients with median baseline Lp(a) 200.0 nmol/L led to a large reduction in LDL-C and a small reduction in Lp(a), resulting in persistent elevated Lp(a) levels. The latter may have contributed to the unaltered arterial wall inflammation.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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