Physicians' Academy for Cardiovascular Education

No interindividual variation in robust LDL-c reduction with PCSK9 inhibition in CVD

Interindividual Variation in Low-Density Lipoprotein Cholesterol Level Reduction With Evolocumab An Analysis of FOURIER Trial Data

Literature - Qamar A, Giugliano RP, Keech AC et al. - JAMA Cardiology 2018: published online ahead of print

Introduction and methods

It has been shown that inhibition of proprotein convertase subtilisinkexin type 9 (PCSK9) with evolocumab reduces LDL-c levels and the risk of CV events in patients with stable atherosclerotic CVD on background statin therapy [1]. However, the interindividual variability in LDL-c reduction in response to PCSK9 inhibitors is unclear and its magnitude has not been defined in a large-scale trial. This subanalysis (n=21.768) of the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial therefore examined the interindividual variability in LDL-c level reduction in response to PCSK9 inhibition with evolocumab.

The FOURIER trial randomized 27.564 patients with prior myocardial infarction, non-hemorrhagic stroke, or symptomatic peripheral artery disease, and LDL-c levels ≥70 mL/dL (1.8 mmol/L) or HDL-c levels ≥100 mg/dL (2.59 mmol/L) while taking background lipid-lowering therapies to either evolocumab or placebo.

Interindividual variation was assessed as percentage reduction in LDL-c from baseline with evolocumab vs. placebo at week 4 and over the course of the first year.

Main results

LDL-c reduction with evolocumab

LDL-c reduction with placebo

Placebo-adjusted LDL-c reduction with evolocumab


In this subanalysis of the FOURIER trial evolocumab reduced LDL-c levels by ≥50% in more than 90% of CVD patients and by ≥30% in more than 99% of CVD patients. These results provide reassurance that LDL-c level can be robustly reduced with evolocumab without concern for variation in response to treatment in CVD patients on background lipid-lowering treatment.


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Find this article online at JAMA Cardiology

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