Real-world effectiveness of monoclonal antibody inhibitors of PCSK9 in patients with heterozygous familial hypercholesterolemia: A retrospective cohort study.

Background: Heterozygous familial hypercholesterolemia (HeFH) is a genetic condition that is associated with a high risk of atherosclerotic cardiovascular disease (ASCVD) due to elevated lipid levels. Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody inhibitors have been shown to reduce low-density lipoprotein cholesterol (LDL-C) substantially. This study aimed to assess the real-world effectiveness of PCSK9 inhibitor therapy among patients with HeFH.

Methods: Retrospective cohort study of patients with probable or definite HeFH on a PCSK9 inhibitor at a specialized lipid clinic between 2015 and 2022. The primary objective was the proportion of patients who attained a ≥50% reduction in LDL-C after 12 months of treatment.

Results: In total, 141 patients were screened and 95 were included. Mean age was 63 years, 51% were female, and mean baseline LDL-C level was 4.0 mmol/L (155 mg/dL). A majority of patients (60%) had statin intolerance, and 73% were on ezetimibe. The most common PCSK9 inhibitor was evolocumab (94%). Overall, 74% of patients achieved a ≥50% reduction in LDL-C after 12 months of therapy. Mean LDL-C concentration decreased to 1.7 mmol/L (66 mg/dL) (approximately 59% reduction from baseline) after 12 months of follow-up but increased to 1.9 mmol/L (73 mg/dL) after ≥24 months of follow-up. Similar trends were observed in non-high-density lipoprotein cholesterol and apolipoprotein B. Lipoprotein(a) was significantly reduced by 45% over 12 months. Twelve percent of patients permanently discontinued therapy. Barriers to PCSK9i use were mostly related to cost.

Conclusions: In a real-world cohort of HeFH patients, most of which were intolerant to statins, a high majority were able to achieve a ≥50% reduction in LDL-C after 12 months of PCSK9 inhibitor therapy (mean reduction of approximately 59%), which is similar to clinical trial data of patients with ASCVD. A significant reduction in non-high-density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a) were also observed.