Physicians' Academy for Cardiovascular Education

Risk of aorta stenosis events reduced by PCSK9i

News - Apr. 23, 2020

PCSK9 inhibition and aortic stenosis in the FOURIER trial

Presented at ACC.20 by Brian Bergmark, MD (Boston, MA, USA)

Introduction and methods

Calcific aortic valve stenosis is a common and morbid condition with a ~5% prevalence in older adults and 25-50% 1-year mortality for untreated symptomatic severe aorta stenosis (AS). Despite rapidly evolving valve replacement techniques, there is no disease modifying pharmacotherapy for AS.

A relation between Lp(a), LDL-c and AS has been suggested based on the following.

First, it has been recognized that the pathobiology of aortic valve stenosis may be similar to that of atherosclerosis. Second, there are epidemiological associations between elevated Lp(a), LDL-c and AS. Third, there are genetic associations between LPA variants, increased Lp(a) concentrations and increased AS incidence, and between PSCK9 sequence variants, decreased Lp(a) and decreased AS incidence. Finally, it has been shown that monoclonal antibodies against PCSK9 reduce Lp(a) concentrations by 20-30% and LDL-c levels by 50-60%. This post-hoc analysis of FOURIER trial data therefore evaluated whether PCSK9 inhibition reduces AS events.

In the FOURIER trial, high-risk, stable patients with established CV disease on statin therapy and LDL-c ≥70 mg/dL or non-HDL-c ≥100 mg/dL were randomized to receive either the PCSK9 inhibitor evolocumab or placebo. This analysis evaluated whether evolocumab reduces AS events in patients with prior ASCVD and investigated associations between lipid concentrations (Lp(a) and LDL-c) and AS events. The safety database was searched for events related to new or worsening AS, or aortic valve replacement (AVR) (transcatheter AVR or surgical AVR). 63 events were identified of which 26 were AVR (18 surgical, 7 transcatheter, 1 unspecified).

Main results


This post-hoc analysis of the FOURIER trial showed a significant association between achieved Lp(a) concentration and future AS events. A beneficial effect of evolocumab was found after 1 year of treatment with a 52% lower rate of AS events compared to placebo. These findings are exploratory and validation in a RCT is required.

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