The class
Modeling shows adding a CETP inhibitor would push LDL-target attainment above 95 percent in familial hypercholesterolemia, versus just 54 percent with ezetimibe alone (J Clin Lipidol 2018)
Original title: Achieved LDL cholesterol levels in patients with heterozygous familial hypercholesterolemia: A model that explores the efficacy of conventional and novel lipid-lowering therapy
Because many patients with heterozygous familial hypercholesterolemia (heFH) fail to reach guideline LDL cholesterol targets, researchers modeled treatment-target attainment in 1,059 heFH patients with coronary heart disease and 9,420 without, across four scenarios of increasing LDL reduction representing maximal-dose statin, statin plus ezetimibe, addition of a CETP inhibitor, and addition of a PCSK9 inhibitor. With 100% adherence, maximal-dose statin alone achieved targets in 8.3% (with CHD) and 48.1% (without CHD) of patients, rising to 54.3% and 93.2% with ezetimibe added, then to 95.7% and 99.7% with a CETP inhibitor added, and to 99.8% and 100% with a PCSK9 inhibitor added. Using literature-based adherence rates of 62% to 80% instead, these figures dropped substantially, to 31.4% and 81.2% with CETP inhibitor addition and 40.3% and 87.1% with PCSK9 inhibitor addition, showing that while CETP inhibitors could theoretically close much of the treatment gap in heFH, realistic adherence would blunt this benefit considerably.
Original abstract
Background: A large proportion of patients with heterozygous familial hypercholesterolemia (heFH) do not reach low-density lipoprotein cholesterol (LDL-c) levels advocated by international guidelines (<70 mg/dL or <100 mg/dL).
Objective: We set out to model which proportion of patients reach targets using conventional and novel therapies.
Methods: We performed a cross-sectional analysis in a large cohort of genetically identified heFH patients and calculated the proportion reaching treatment targets in four scenarios: (1) after 50% LDL-c reduction (representing maximal dose statin); (2) after 70% LDL-c reduction (maximal dose statin + ezetimibe); (3) additional 40% LDL-c reduction representing cholesteryl ester transfer protein inhibitor (CETPi); and (4) 60% LDL-c reduction (proprotein convertase subtilisin/kexin type 9 inhibitors [PCSK9i]), on top of scenario 2. We applied 100% adherence rates and literature-based adherence rates from 62% to 80%.
Results: We included 1,059 heFH patients with and 9,420 heFH patients without coronary heart disease (CHD). With maximal dose statin, 8.3% and 48.1% of patients with and without CHD would reach their recommended LDL-c targets, respectively. This increases to 54.3% and 93.2% when ezetimibe is added. Addition of CETPi increases these numbers to 95.7% and 99.7%, whereas adding PCSK9i would result in 99.8% and 100% goal attainment. Using literature-based adherence rates, these numbers decrease to 3.8% and 27.3% for maximal dose statin, 5.8% and 38.9% combined with ezetimibe, 31.4% and 81.2% when adding CETPi, and 40.3% and 87.1% for addition of PCSK9i.
Conclusions: Less than 10% with and 50% of heFH patients without CHD would reach treatment targets with maximal dose statin, but this substantially increases on addition of ezetimibe, CETPi, or PCSK9i. However, considering recently published adherence data, this might be lower in real life, especially in heFH patients with CHD.
the classfamilial hypercholesterolaemia
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.