Persistent arterial wall inflammation in patients with elevated lipoprotein(a) despite strong low-density lipoprotein cholesterol reduction by proprotein convertase subtilisin/kexin type 9 antibody treatment.

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.

• Authors: Lotte C A Stiekema, Erik S G Stroes, Simone L Verweij, Helina Kassahun, Lisa Chen, Scott M Wasserman, Marc S Sabatine, Venkatesh Mani, Zahi A Fayad
• Journal: European heart journal (Eur Heart J) Vol. 40 Issue 33 Pg. 2775-2781 (09 01 2019) ISSN: 1522-9645 [Electronic] England
• PMID: 30561610 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: [email protected].

Chemical References

• Antibodies, Monoclonal, Humanized
• Anticholesteremic Agents
• Cholesterol, LDL
• Lipoprotein(a)
• PCSK9 protein, human
• Proprotein Convertase 9
• evolocumab

Topics

• Aged
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Anticholesteremic Agents (therapeutic use)
• Arteritis (blood, drug therapy)
• Cholesterol, LDL (antagonists & inhibitors)
• Double-Blind Method
• Female
• Humans
• Lipoprotein(a) (blood)
• Male
• Middle Aged
• Proprotein Convertase 9 (therapeutic use)
• Treatment Failure