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Delainy was the most difficult of these, representing everyone from Orz to Indat and Eleranian. Character Designer What's New In? Efficacy of a first-generation PCSK9 inhibitor in patients with heterozygous familial hypercholesterolemia and statin intolerance or non-response: 12-month results from the FOURIER trial. PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors reduce low-density lipoprotein (LDL)-cholesterol (C). We assessed the effect of evolocumab on lipids in patients with heterozygous familial hypercholesterolemia (HeFH) and statin intolerance, or non-response, and whether the response was affected by the PCSK9 mutational subtype. In the FOURIER (FOrcery Of protein-cysKine Inhibition Evaluation in Renal disease) trial, adults with HeFH (n = 1433) were randomized to 12 months of double-blind, placebo-controlled, repeat treatment with evolocumab 420 mg Q4W or 420 mg Q2W. Preplanned subgroup analyses of the HeFH cohort for change in mean lipid levels were performed in pts stratified by PCSK9 mutational subtype [rs1410996 (E167D), rs7566605 (I384V), both combined], and type of response to statin-based therapy [any statin treatment response (ATS)]. Evolocumab was associated with significant, dose-dependent reductions in LDL-C, apolipoprotein B, and non-high-density lipoprotein C (non-HDL-C). Patients treated with 420 mg Q4W had significantly lower LDL-C (-49.1%) and apolipoprotein B (-24.5%) than placebo in all patients [Evo420 (EvoQ4W) vs. placebo] (P ≤ 0.0021 for both). Compared with placebo, evolocumab reduced LDL-C by 42.6% and apolipoprotein B by 30.5% in the E167D-allele group and 61.7% and 59.3% in the I384V-allele group (P < 0.0001 for each allele group) and 36.3% and 31.5% (both P < 0.0001) in the combined group. 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