Impact of PCSK9 inhibitors on plasma lipoprotein(a) concentrations with or without a background of niacin therapy

Background: Lipoprotein(a) [Lp(a)] is an atherogenic lipoprotein associated with atherosclerotic cardiovascular disease. Niacin and proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) both lower Lp(a).

Objective: The objective of the study was to determine if addition of PCSK9i to background niacin therapy further lowers Lp(a).

Methods: This study is a retrospective analysis of patients who met the following inclusion criteria: initiated PCSK9i therapy, had Lp(a) measurements before and after initiation of PCSK9i, and for the combination therapy group, PCSK9i was added on top of baseline niacin monotherapy. Of the 150 patients included in this study, 136 were on monotherapy (PCSK9i) and 14 were on combination therapy (niacin + PCSK9i). Lp(a) values were assessed in both groups before and after the addition of PCSK9i.

Results: Median percent and absolute Lp(a) reductions in the niacin + PCSK9i combination therapy group were -15.3% (interquartile range [IQR] -31.8, -1) and -9 mg/dL (IQR -37.2, -0.5), respectively, from a baseline Lp(a) of 95 mg/dL (IQR 20.5, 171). These reductions were statistically significant or nearly so (P = .04 and P = .05, respectively). Median percent and absolute Lp(a) reductions in the PCSK9i monotherapy group were -17.3% (IQR -34.4, 0) and -6 mg/dL (IQR -16, 0), respectively, from a baseline Lp(a) of 39.5 mg/dL (IQR 15, 117.5). There was no difference in median percent and absolute change in Lp(a) between monotherapy and combination therapy groups (P = .84 and P = .54, respectively).

Conclusions: Our study demonstrates that the addition of PCSK9i to background of niacin therapy is associated with ∼15% reduction in Lp(a) beyond that achieved with background niacin monotherapy.