Ineffective Subtilisin/Kexin Type 9 (PCSK9) Inhibitors Monotherapy in Dyslipidemia with Low-Density Lipoprotein Cholesterol (LDL-C) Receptor Abnormalities: A Report of 2 Cases

Abstract

Case series Patients: Male, 44-year-old • Female, 71-year-old Final Diagnosis: Resistance to PCSK9I overcomed by adding statin Symptoms: Dyslipidemia Medication: — Clinical Procedure: — Specialty: Cardiology Objective: Unusual or unexpected effect of treatment Background: Real-life data on the efficacy of monotherapy with PCSK9 inhibitors are scarce. Most cohort studies have examined populations that are not severely dyslipidemic and are receiving combined therapy rather than monotherapy. Case Reports: From a series of 167 alirocumab prescriptions, we present a case of complete nonresponse and one of low response to monotherapy with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in 2 patients with heterozygous familial hypercholesterolemia and abnormalities of the low-density lipoprotein cholesterol (LDL-C) receptor. In these cases, PCSK9 inhibitors were ineffective when used alone to reduce the LDL-C level, but the addition of statin led to a dramatic improvement. Conclusions: As PCSK9 inhibitors become more commonly prescribed, more cases of nonresponse to PCSK9 inhibitors will be identified. Prospective studies are needed to investigate the efficacy of treatment with the monoclonal antibodies PCSK9 inhibitors in the context of LDL-C receptor abnormalities and to determine whether a genetic explanation exists for interindividual differences in response.

Real-World Efficacy of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (PCSK9i) in Heterozygous Familial Hypercholesterolemia Patients Referred for Lipoprotein Apheresis

“…The real-world efficacy of PCSK9i regarding patients’ characteristics and the severity of LDL-c levels are not known since the vast majority of randomized controlled trials have been conducted on patients receiving combination therapy (PCSK9i and statin), and patients with low LDL-c before treatment [ 11 – 14 ]. Therefore, we aimed to investigate the variation in LDL-c levels after initiation of PCSK9i, either as monotherapy, or in combination with previously prescribed ezetimibe or statin plus ezetimibe in a real-life cohort study of severely dyslipidemic heterozygous FH patients referred for lipoprotein apheresis.…”