Abstract:

Background: Lipoprotein(a) [Lp(a)] has been independently associated with increased cardiovascular risk.

Objective: We examined the effect of monoclonal antibody proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) on plasma Lp(a) levels across multiple trials.

Methods: Studies were retrieved comparing the effect of PCSK9i vs. placebo on Lp(a) levels. The primary outcome was percent change in Lp(a) levels. Factors associated with the treatment effect were determined by meta-regression analysis. Subgroup analyses were done to explore potential treatment effect differences.

Results: PCSK9i reduced Lp(a) levels on average of -27% (95% CI: -29.8 to -24.1, p<0.001). Factors associated with the treatment effect included mean percent change in LDL C (p=0.003, beta coefficient 0.34, 95% CI: 0.11-0.57), tau2=94.8, R2=11.82) and ApoB (p<0.002, beta coefficient 0.4, 95% CI: 0.14-0.64), tau2=93.68, R2=11.86). Subgroup analyses revealed consistent treatment effect amongst comparators (vs. placebo: -27.69% (95% CI: - 30.85 to -24.54, p<0.001), vs. ezetimibe: -24.0% (95% CI: -29.95% to -18.01, p<0.001), type of PCSK9i, evolocumab: -29.35% (95% CI: -33.56 to -25.14, p<0.001) vs. alirocumab: -24.50% (95% CI: -27.96 to -21.04, p<0.001), and presence of FH: -25.63% (95% CI: -31.96% to -19.30, p<0.001 vs. no FH: -27.22% (95% CI: -30.34. to -24.09, p<0.001). Varying treatment effects were noted in the duration of treatment (12 weeks or shorter: -32.43% (95% CI: -36.63 to -28.23 vs. >12 weeks: -22.31% (95% CI: -25.13 to -19.49, p<0.001), p interaction <0.01.

Conclusion: PCSK9 inhibitors reduce Lp(a) levels by an average of 27%. Mean percent change in LDL-C and ApoB were associated with treatment effect.

JACC: Advances Editor-in-Chief 

Candice K. Silversides, MD, FACC

JACC: Advances CME Editor

Kenneth A. Ellenbogen, MD

Author

Barbara S. Wiggins, PharmD, FACC

Important Dates

Date of Release: February 26, 2025 

Term of Approval/Date of CME/MOC Expiration: February 25, 2026