European Primary Care Cardiovascular Society

Lower achieved LDL-c levels associated with lower CV risk in ASCVD

Association Between Achieved Low-Density Lipoprotein Cholesterol Levels and Long-Term Cardiovascular and Safety Outcomes: An Analysis of FOURIER-OLE

Literature - Gaba P, O'Donoghue ML, Park JG, et al. - Circulation. 2023 Feb 13. [Online ahead of print]. doi: 10.1161/CIRCULATIONAHA.122.063399.

Introduction and methods


Elevated LDL-c levels are a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD) [1]. The FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) and the FOURIER-OLE (FOURIER Open-Label Extension) trials demonstrated that PCSK9i evolocumab reduced LDL-c and lowered the short and long-term risk of CV events [2-3]. However, it remains uncertain what the optimal long-term LDL-c levels are with regards to cardiovascular and safety outcomes.

Aim of the study

The authors investigated the relationship between achieved LDL-c levels with evolocumab and the occurrence of long-term adverse cardiovascular and safety outcomes.



The FOURIER trial was a randomized, double-blind, placebo-controlled trial, with 27,564 patients with stable ASCVD. Patients had baseline LDL-c concentrations of ≥70 mg/dL or non-HDL-c levels ≥100 mg/dL while on optimized lipid-lowering therapy, including a high- or moderate-intensity statin with or without ezetimibe. Patients were randomized to subcutaneous evolocumab (either 140 mg every 2 weeks or 420 mg once per month) or matching placebo. The median follow-up was 2.2 years.

6635 patients of the FOURIER trial were enrolled in the FOURIER-OLE trial. Patients received subcutaneous evolocumab (either 140 mg every 2 weeks or 420 mg once per month), regardless of initial allocation in the parent trial. For this prespecified secondary analysis, data of 6559 patients with achieved LDL-c levels (average of the first 2 LDL-c measurements at weeks 12, 24, or 48) were available. Patients were categorized in 5 different categories based on the achieved LDL-c levels: <20 mg/dL, 20 to <40 mg/dL, 40 to <55 mg/dL, 55 to <70 mg/dL, or ≥70 mg/dL. The median follow-up was 4.8 years. The maximum follow-up was 8.6 years in the entire FOURIER and FOURIER-OLE cohort.


The primary efficacy outcome was the composite of CV death, MI, stroke, coronary revascularization, or hospital admission for unstable angina. The key secondary efficacy outcome was the composite of cardiovascular death, MI, or stroke.

Main results


The authors demonstrate that achievement of lower LDL-c levels in patients with ASCVD is associated with a reduced long-term risk of cardiovascular outcomes, without any serious safety concerns.


Show references

Find this article online at Circulation.

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