Physicians' Academy for Cardiovascular Education

Greater LDL-c reduction by PCSK9i in FH patients in time-averaged analysis

Time-averaged low-density lipoprotein cholesterol lowering with evolocumab: Pooled analysis of phase 2 trials

Literature - Schludi B, Giugliano RP, Sabatine MS, et al. - J Clin Lipidol. 2022 Jun 6;S1933-2874(22)00174-X. doi: 10.1016/j.jacl.2022.05.069.

Introduction and methods


In the long term, the PCSK9 inhibitor evolocumab lowers LDL-c concentration by approximately 60%, compared with placebo, according to multiple randomized trials [1-3]. However, in these trials, the effect of evolocumab was evaluated at the end of the dosing interval (i.e., the trough of drug effect), which may underestimate the treatment effect. To more accurately determine the effect of evolocumab, it is better to average the LDL-c concentration over a longer period of time, which includes both peaks and troughs of the drug effect.

Aim of the study

This pooled analysis of data from patients with familial hypercholesterolemia from multiple phase 2 studies examined the LDL-c lowering effect of evolocumab based on time-averaged measurements and compared it with placebo.


The researchers conducted a pooled analysis of data from 5 phase 2 studies in which patients with familial hypercholesterolemia (n=372) were randomized to evolocumab (140 mg every 2 weeks or 420 mg monthly) or placebo. Patient data were used only if the patient's LDL-c concentration had been measured at baseline and he or she was still being treated with evolocumab or placebo after 8 and 10 weeks (when treated every 2 weeks) or after 8 weeks (when treated monthly). LDL-c concentration was calculated using both the Martin-Hopkins formula and the Friedewald formula. For each patient, the percentage decrease in LDL-c concentration relative to the LDL-c concentration at baseline was averaged over a 4-week period (weeks 9-12). A similar analysis was performed for the serum concentration of free PCSK9.


The researchers were interested in the time-averaged percent reduction in concentrations of LDL-C and free PCSK9 by treatment with evolocumab, compared with placebo.

Main results


This pooled analysis shows that the LDL-c lowering effect of evolocumab is greater when the LDL-c concentration is averaged over a longer period of time rather than measured at the end of the dosing interval. The authors concluded that time-averaged measurements of the LDL-c concentration may better reflect the likely long-term treatment effect of PCSK9 inhibitors.


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Find this article online at J Clin Lipidol.

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