Impact of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors on Lipoprotein(a) A Meta-Analysis and Meta-Regression of Randomized Controlled Trials (JACC: Advances February 2025)-Article: Impact of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors on Lipoprotein(a) A Meta-Analysis and Meta-Regression of Randomized Controlled Trials

Article: Impact of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors on Lipoprotein(a) A Meta-Analysis and Meta-Regression of Randomized Controlled Trials

Back to course

Pdf Summary

This study is a comprehensive meta-analysis investigating the impact of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9 inhibitors or PCSK9i) on lowering lipoprotein(a) [Lp(a)] levels, a lipid associated with cardiovascular risk. The research encompasses 47 randomized controlled trials involving 67,057 participants and evaluates PCSK9i effectiveness compared to placebo and ezetimibe, a cholesterol-lowering medication.<br /><br />The primary finding reveals that PCSK9i therapy reduces Lp(a) levels by an average of 27%, with variations noticed based on factors such as treatment duration, type of PCSK9i used, and the presence of familial hypercholesterolemia. More significant reductions in Lp(a) were associated with greater reductions in low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (ApoB). Interestingly, a notable distinction in Lp(a) reduction was seen between treatment durations of less or more than 12 weeks, with more pronounced effects in the initial 12 weeks.<br /><br />Additionally, the study highlights the broader lipid-lowering effects of PCSK9i, which include substantial reductions in LDL-C by 52.41%, non-high-density lipoprotein cholesterol by 46.48%, total cholesterol by 34.42%, and triglycerides by 11.11%, while increasing high-density lipoprotein cholesterol by 5.98%.<br /><br />Despite the reported reductions in Lp(a) and other lipids, the meta-analysis suggests that while PCSK9i appears consistently effective, there is still a need for further exploration into its long-term impact on cardiovascular outcomes specifically related to elevated Lp(a) levels. The study acknowledges the limitations regarding individual patient data and calls for more nuanced research to understand fully how variables like race and duration of therapy influence outcomes. <br /><br />Emerging therapies and ongoing trials, such as those directly targeting Lp(a), are anticipated to provide deeper insights into the optimal management of heightened cardiovascular risks associated with elevated Lp(a) levels.

Keywords

PCSK9 inhibitors

lipoprotein(a)

cardiovascular risk

meta-analysis

randomized controlled trials

LDL-C reduction

familial hypercholesterolemia

lipid-lowering effects

long-term impact

emerging therapies