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

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.

Automated summary

PCSK9mAbs can effectively and safely lower plasma Lp(a) concentrations in patients with elevated Lp(a) in clinical practice, with significant reductions in LDL-C, remnant-cholesterol, and apolipoprotein B concentrations as well.