Physicians' Academy for Cardiovascular Education

Treatment effect of PCSK9-inhibitor on major coronary events by baseline Lp(a) level in ASCVD

Lipoprotein(a), PCSK9 Inhibition and Cardiovascular Risk: Insights from the FOURIER Trial

Literature - O’Donoghue ML, Fazio S, Giugliano RP et al. - Circulation 2018: published online ahead of print

Introduction and methods

Higher plasma lipoprotein(a) (Lp[a]) levels are associated with the development of CAD [1-2]. However, there are only few treatments that can reduce Lp(a) levels and it remains unknown whether reducing Lp(a) levels will translate into improved CV outcomes [3-5]. Although proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to significantly reduce plasma Lp(a) concentrations by ~25-30% [6-8], it remains unknown whether the effect of evolocumab on risk of coronary events is dependent on baseline Lp(a) levels. This analysis of the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial therefore investigated the relationship between Lp(a) levels, PCSK9 inhibition with evolocumab, and CV risk reduction.

The randomized, double-blind, placebo-controlled FOURIER trial randomized 25.096 patients aged 40-85 years with established atherosclerotic CVD (ASCVD), fasting LDL-c levels ≥70 mg/dl (1.8 nmol/L) or non-HDL-c levels ≥100mg/dl (2.6 nmol/L), who were on optimized lipid-lowering therapy, to receive either evolocumab or placebo. Participants were followed for a median of 2.2 years and stratified into quartiles based on baseline Lp(a) levels. Event rates were estimated at 3 years using the Kaplan-Meier method.

The outcome was major coronary events, consisting of coronary heart disease (CHD) death, myocardial infarction (MI) and urgent coronary revascularization.

Main results

Treatment effect of evolocumab on Lp(a) levels after 48 weeks

Treatment effect of evolocumab on major coronary events by baseline Lp(a) level

Risk of CHD events by achieved Lp(a) and LDL-c levels at week 12


Results of a subanalysis of the FOURIER trial showed that evolocumab significantly reduced Lp(a) levels compared to placebo. Moreover, patients with higher baseline Lp(a) levels experienced greater absolute reductions in Lp(a) levels and non-significant greater coronary benefit from PCSK9 inhibition, compared to those with low baseline Lp(a) levels.


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Find this article online at Circulation

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