Qamar A, et al. - In this analysis of the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial data, researchers investigated the extent to which interindividual variability can be seen in low-density lipoprotein cholesterol levels (LDL-C) reduction with the proprotein convertase subtilisin kexin 9 (PCSK9) inhibitor evolocumab. Evolocumab use appeared to result in a highly consistent robust reduction in LDL-C levels.

Methods

• In a placebo-controlled randomized clinical trial, named the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial, the PCSK9 inhibitor evolocumab was tested in patients with stable atherosclerotic cardiovascular disease who were taking statin medications.
• Researchers examined the percentage change in LDL-C levels from baseline in this trial.
• Primary analysis was performed excluding patients in either treatment arm who had high baseline LDL-C variability during screening and either did not receive the study drug, altered their background lipid-lowering therapy regimen, or had no LDL-C level sample in week 4.
• Analyses were stratified by treatment arm.
• Data was obtained from 2013 to 2016, and data analysis was carried out from January 2018 to November 2018.
• Interindividual variation in percent reduction in LDL-C with evolocumab was assessed.

Results

• The cohort comprised 27,564 subjects; 21,768 patients remained after exclusions for baseline variability (n=3,524) or alterations in background lipid therapy and other causes (n=2,272).
• LDL-C levels from baseline were reduced by a median percentage of 66% with evolocumab at week 4 (interquartile range, 54%-76%; median [interquartile range] baseline value, 90 [79-105] mg/dL; postchange value, 31 [21-44] mg/dL).
• The first year reduction in LDL-C levels was 50% or greater in 10,325 of 10,902 patients in the evolocumab group (94.7%), 30% or more in 10,669 of 10,902 (97.9%), and 10,849 of 10,902 (99.5%) had any reduction in LDL-C levels.
• No apparent reduction in LDL-C levels was seen in 53 patients (0.5%).
• At 4 weeks, placebo arm showed the median LDL-C reduction of 4% (interquartile range, 6% increase to 13% reduction; baseline median [IQR] value, 90 [79-106] mg/dL; postchange value, 87 [74-103] mg/dL).
• For both evolocumab and placebo groups, notable variability was shown in waterfall plots between the top and bottom 5% of patients, with large changes in LDL-C levels in the placebo group (increases of ≥25%, 531 patients [4.9%]; decreases of ≥25%, 985 patients [9.1%]).
• With evolocumab, the placebo-adjusted reductions in LDL-C levels were 50% or greater in 9,839 of 10,866 patients (90.5%) and 30% or greater in 10,846 of 10,866 patients (99.8%) at 4 weeks.
• Across clinically relevant subgroups, consistent findings were seen.