Physicians' Academy for Cardiovascular Education

Continued efficacy of LDL-c lowering, even below 40 mg/dL, in high risk patients

Cardiovascular Benefit of Lowering LDL Cholesterol Below 40 mg/dl

Literature - Marston NA, Giugliano RP, Park J-G et al., - Circulation 2021, 10.1161/CIRCULATIONAHA.121.056536

Introduction and methods

In the FOURIER trial, LDL-c levels were lowered by the PCSK9 inhibitor evolocumab from a median of 93 mg/dL to 30 mg/dL [1]. It is unknown however whether there is still additional benefit of lowering LDL-c below thresholds in the guidelines, for example below 40 mg/dL.

Therefore, an exploratory analysis of FOURIER was conducted utilizing comparisons of randomized groups and analyzing in the context of the magnitude of LDL-c lowering below targets.

FOURIER was a CV outcomes trial in which evolocumab was compared to placebo in 27,564 patients with stable ASCVD on optimal statin therapy [1]. Endpoint was major adverse cardiovascular events (MACE), defined as CV death, MI or stroke. Median follow-up was 2.2 years. Ultracentrifugation was done when LDL- c was <40 mg/dL. 65% of Patients on evolocumab achieved an LDL <40 mg/dL.

Main results


This exploratory analysis of FOURIER showed that lowering LDL-c below 40 mg/dL results in continued benefit with regard to MACE reduction in patients with ASCVD.


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Find this article online at Circulation

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