RNA therapeutics
Combining PCSK9 inhibitors with apo(a) antisense therapy may best address residual risk in the 1 in 3 FH patients with high Lp(a), a review (Eur Heart J 2017)
Original title: Depicting new pharmacological strategies for familial hypercholesterolaemia involving lipoprotein (a)
This review by Vuorio, Watts and Kovanen addresses new pharmacological strategies for heterozygous familial hypercholesterolaemia (HeFH), a condition affecting approximately 35 million people worldwide, one in three of whom also inherit elevated Lp(a). Neither statins nor ezetimibe lower Lp(a), leaving HeFH patients with high Lp(a) at high residual atherosclerotic cardiovascular disease risk. PCSK9 monoclonal antibodies, indicated for HeFH patients not at guideline LDL cholesterol targets, lower Lp(a) by only 15-30%, whereas newer apo(a) antisense therapy trials show more potent reductions of up to 90%. The authors propose combining a PCSK9 inhibitor with apo(a) antisense therapy as the optimal strategy to mitigate residual cardiovascular risk in HeFH patients with high Lp(a).
Original abstract
Approximately 35 million people worldwide suffer from heterozygous familial hypercholesterolaemia (HeFH), a condition characterized by genetically determined life-long elevation of plasma low-density lipoprotein cholesterol (LDL-C). One in three of these patients also inherit an elevated plasma concentration of lipoprotein (a) [Lp(a)], a lipoprotein particle with atherogenic, inflammatory and prothrombotic properties. Accordingly, the combination of high plasma LDL-C and Lp(a) can markedly accelerate premature atherosclerotic cardiovascular disease (ASCVD). Neither statin nor ezetimibe lowers Lp(a), so that FH patients with high Lp(a) remain at high residual risk of ASCVD. PCSK9 monoclonal antibodies are indicated for HeFH patients not at guideline-recommended LDL-C target, but only lower Lp(a) concentration by 15-30%. Recent trials employing apo(a) antisense therapy show more potent (up to 90%) reductions in plasma Lp(a). The combination of PCSK9 inhibitor and apo(a) antisense therapy appears the optimal strategy for mitigating residual risk of ASCVD in HeFH patients with high Lp(a).
familial hypercholesterolaemiaPCSK9 inhibitionRNA therapeutics
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.