Simulation of low-density lipoprotein cholesterol goal attainment with treatment intensification in a population with homozygous familial hypercholesterolemia

Background Most people with homozygous familial hypercholesterolemia (HoFH) do not achieve guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals despite standard-of-care (SOC) lipid-lowering therapies (LLTs). Here, we estimate the proportion of individuals with HoFH achieving guideline-recommended LDL-C goals of <100 mg/dL, <70 mg/dL, and <55 mg/dL after treatment intensification. Methods A simulation model explored LLT intensification strategies with statin, ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i), evinacumab, lomitapide, and/or lipoprotein apheresis for LDL-C goal attainment. Baseline LLTs and LDL-C levels were obtained from 78 participants with HoFH in the CASCADE FH registry. Results Adding evinacumab or lomitapide (10 mg/day) to SOC enabled an estimated 80.1% and 59.3% of individuals to reach LDL-C <100 mg/dL, respectively; biweekly apheresis plus SOC enabled 65.4%. Combining evinacumab and apheresis with SOC raised attainment of <100 mg/dL to 95.6%, and adding lomitapide further increased attainment to 96.7%. For more stringent goals of LDL-C <70 mg/dL and <55 mg/dL, 50.9% and 29.8% of individuals achieved these goals with evinacumab plus SOC, respectively, and 80.8% and 64.6% with evinacumab, apheresis, plus SOC. Combining all three advanced therapies (evinacumab, lomitapide, and apheresis) with SOC enabled most people to reach goals of <70 mg/dL (92.4%) and <55 mg/dL (79.7%). Conclusions Simulation findings indicate that most people with HoFH require aggressive treatment intensification with advanced LLTs to achieve guideline-recommended LDL-C goals. Evinacumab with/without apheresis or lomitapide represents a highly effective treatment strategy. Our findings support earlier escalation to advanced LLTs when SOC is unlikely to be sufficient.