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
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 . 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 . 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.
- The further baseline LDL-c levels were <93 mg/dL, the greater the proportion of LDL-c lowering was <40 mg/dL.
- A consistent benefit on MACE of LDL-c lowering was seen regardless of how low the baseline LDL-c was (and lower LDL-c baseline was associated with greater proportion of patients reaching LDL-c <40 mg/dL) (Pinteraction=0.78).
- A similar pattern was seen for apoB and non-HDL-c lowering.
- There was no difference in absolute risk reduction at lower baseline LDL-c.
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.