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.

Lipoprotein(a) and Cardiovascular Disease: A Missing Link for Premature Atherosclerotic Heart Disease and/or Residual Risk

“…A more recent open-label study investigated the effect of treatment with evolocumab or alirocumab of 53 patients with elevated Lp(a) level ($0.5 g/L) over a mean of 11 months. 116 Administration of a PCSK9mAb led to a significant decrease of 0.29 g/L (222%) in Lp(a) levels (P , 0.001). Besides, there were significant decreases in LDL cholesterol (LDL-C) (253%), apolipoprotein B (243%), and remnant-cholesterol (212%) levels.…”

Atherogenic Dyslipidemias: Unmet Needs and the Therapeutic Potential of Emerging and Novel Approaches and Drugs

“…Such an intense effect could be obtained thus far only acutely by using lipoprotein apheresis, but the mean interval reductions with weekly or biweekly procedures reach around 25–40% [ 105 ]. In fact, Lp(a) levels are not reduced by SCLT and may even be slightly increased (10–20%) by statins [ 106 ], whereas the Lp(a)-lowering effect of PCSK-9 inhibitors is modest with a 20–30% reduction [ 107 , 108 ]. Specific Lp(a)-lowering drugs that target the production of apolipoprotein(a) were recently developed, and some of them are at an advanced stage in clinical research assessment.…”

Lipoprotein(a) in patients with breast cancer after chemotherapy: exploring potential strategies for cardioprotection

“…Evolocumab has be proven to decrease LDL-C concentrations to 30 mg per deciliter and reduce the incidence of CVD by inhibiting PCSK9 [96]. PCSK9 mAbs are effective in safely lowering Lp(a) concentration clinical practice, especially in patients with increased Lp(a) concentrations [97,98]. Accordingly, monoclonal antibodies that suppress PCSK9 have become a hopeful choice for reducing Lp(a) levels [99].…”

“…If the LDLR pathway completely explains Lp(a) clearance, it can be expected that PCSK9 inhibitor treatment will uniformly decrease Lp(a) and LDL-C in the same individual in 2:1 ratio (consistent reduction) [102]. In a clinical trial, there was no clear correlation between decrease in Lp(a) and LDL-C after treatment with PCSK9 inhibitors [97]. This inconsistent decline may indicate that PCSK9 inhibitor treatment decreases plasma Lp(a) by an alternative route of LDL receptor removal.…”