Dataset Information

Effectiveness of proprotein convertase subtilisin/kexin-9 monoclonal antibody treatment on plasma lipoprotein(a) concentrations in patients with elevated lipoprotein(a) attending a clinic.

ABSTRACT:

Background

Lipoprotein(a) (Lp[a]) is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Proprotein convertase subtilisin/kexin-9 monoclonal antibodies (PCSK9mAbs) can lower Lp(a) levels in clinical trials, but their effects in patients with elevated Lp(a) in clinical practice remain unclear.

Aims

To investigate the effectiveness and safety of PCSK9mAbs in lowering plasma Lp(a) in patients with elevated Lp(a) concentrations in a lipid clinic.

Methods

This was an open-label study of 53 adult patients with elevated Lp(a) concentration (≥0.5 g/L). Clinical, biochemical, and safety data were collected before and on treatment with evolocumab or alirocumab over a mean period of 11 months.

Results

Treatment with a PCSK9mAb resulted in a significant reduction of 0.29 g/L (-22%) in plasma Lp(a) concentration (p<.001). There were also significant reductions in low-density lipoprotein-cholesterol (LDL-C) (-53%), remnant-cholesterol (-12%) and apolipoprotein B (-43%) concentrations. The change in Lp(a) concentration was significantly different from a comparable group of 35 patients with elevated Lp(a) who were not treated with a PCSK9mAb (-22% vs. -2%, p<.001). The reduction in Lp(a) concentration was not associated with the corresponding changes in LDL-C, remnant-cholesterol, and apolipoprotein B (p>.05 in all). 7.5% and 47% of the patients attained a target concentration of Lp(a) <0.5 g/L and LDL-C <1.8 mmol/L, respectively. PCSK9mAbs were well tolerated, the common adverse effects being pharyngitis (9.4%), nasal congestion (7.6%), myalgia (9.4%), diarrhoea (7.6%), arthralgia (9.4%) and injection site reactions (11%).

Conclusion

PCSK9mAbs can effectively and safely lower plasma Lp(a) concentrations in patients with elevated Lp(a) in clinical practice; the impact of the fall in Lp(a) on ASCVD outcomes requires further investigation.

SUBMITTER: Chakraborty A

PROVIDER: S-EPMC8207967 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description: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.