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REFLECTIONS
Dyslipidaemia
Dyslipidaemia Global Newsletter #5 2023

Association between achieved low-density lipoprotein cholesterol levels and long-

term cardiovascular and safety outcomes: An analysis of FOURIER-OLE.
Dyslipidaemia
Gaba P, et al. Circulation. 2023 Apr 18;147(16):1192-1203.

Lowering LDL-C levels is a cornerstone of
ASCVD risk reduction; however, the benefits
and safety of very low LDL-C (10–40 mg/dL) has
emerged as a key question.

The Further Cardiovascular Outcomes Research
With PCSK9 Inhibition in Subjects With Elevated
Risk (FOURIER) trial examined 27,564 patients
with stable ASCVD and randomized them to
evolocumab, a PCSK9i, or placebo, with a
median follow-up of 2.2 years. In the open-
label extension (FOURIER-OLE), 6635 of
these patients were transitioned to evolocumab
regardless of initial treatment allocation and
followed for an additional five years.

In this prespecified analysis, the authors
examined the relationship between LDL-C levels
and the incidence of subsequent CV and safety
outcomes. There was a monotonic relationship
between lower achieved LDL-C levels down
to very low levels <20 mg/dL, and a lower risk
of the primary efficacy endpoint (a composite
of CV death, MI, stroke, hospital admission for
unstable angina or coronary revascularization)
and the key secondary endpoint (composite of
CV death, MI, or stroke).

In terms of safety, there was no statistically
significant increase in adverse safety events
with lower levels of achieved LDL-C during
the extended follow-up period, including
neurocognitive events, cataract-related adverse
events, new or progressive malignancy, and
new-onset diabetes.

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