Real-World Effectiveness of PCSK9 Inhibitors in Reducing LDL-C in Patients With Familial Hypercholesterolemia in Italy: A Retrospective Cohort Study Based on the AIFA Monitoring Registries

Abstract

Background Information on the real-world use of proprotein convertase subtilisin kexin 9 inhibitors (PCKS9is) in familial hypercholesterolemia are limited. We evaluated the pattern of prescription and the long-term efficacy of alirocumab and evolocumab in Italian patients with familial hypercholesterolemia in clinical practice. Methods and Results The data set for analysis was extracted from the PCKS9i Italian Medicines Agency (AIFA) registry and included 2484 patients with heterozygous familial hypercholesterolemia (HeFH) and 62 patients with homozygous familial hypercholesterolemia (HoFH) who were prescribed PCKS9is from February 2017 to December 2021. As the follow-up schedules were not prespecified and could vary, persistence and adherence as well as low-density lipoprotein cholesterol (LDL-C) changes during 2 years of treatment were analyzed in a final cohort of 1299 patients with familial hypercholesterolemia. At baseline, 53.8% of patients with HeFH and 69.4% of patients with HoFH were receiving maximally tolerated lipid-lowering therapies, while 45.9% of patients with HeFH and 30.7% of patients with HoFH reported statin intolerance; mean LDL-C was 197.7±52.3 mg/dL in HeFH and 252.0±106.2 mg/dL in HoFH. The 6-month persistence and adherence to therapy were >85%, and LDL-C reduction reached 58.6% (to 79.7 mg/dL) in HeFH and 57.6% (to 95.1 mg/dL) in HoFH after 24 months of treatment. The European Atherosclerosis Society/European Society of Cardiology LDL-C goals were achieved in 43.3% of patients with HeFH and 37.5% of patients with HoFH. Conclusions PCKS9i prescribed to patients with familial hypercholesterolemia in clinical practice showed LDL-C-lowering efficacy similar to that observed in controlled trials. However, 2 of 5 HeFH cases and 2 of 6 HoFH cases achieved the recommended LDL-C goals. The full achievement of European Atherosclerosis Society/European Society of Cardiology LDL-C goals should require a lower threshold for PCKS9i initiation and a combination of multiple therapies.

Keywords: LDL cholesterol; PCSK9 inhibitors; adherence; heterozygous familial hypercholesterolemia; homozygous familial hypercholesterolemia; real‐world.

Figure 1. Flowchart of the population selection.

Depicts the criteria used to select patients eligible for the retrospective observational study among those included in the AIFA wMRs registry. Using standard labeling in longitudinal analyses, selected patients were labeled as stayers; conversely, patients not included in the main follow‐up analysis due to the fact the observations fell out of the prespecified time‐point windows were labeled as attritors. AIFA indicates Italian Medicines Agency; HeFH, heterozygous familial hypercholesterolemia; HoFH, homozygous familial hypercholesterolemia; and wMRs, web platform of monitoring registries.

Figure 2. Distribution of individual LDL‐C values in patients with HeFH and patients with HoFH receiving PCSK9is at the different time points during treatment.

Data are presented as a violin plot according to the different time points. The dotted line corresponds to the mean value of LDL‐C at the first visit. Median values, interquartile ranges, and first and third quartiles are highlighted in the plot. Data are represented for the 6‐, 12‐, 18‐, and 24‐month time points in both HeFH and HoFH. LDL‐C values are expressed as mg/dL. Individual LDL‐C values in HeFH (A), and those in patients with HoFH (B). HeFH indicates heterozygous familial hypercholesterolemia; HoFH, homozygous familial hypercholesterolemia; LDL‐C, low‐density cholesterol; and PCKS9i, proprotein convertase subtilisin/kexin type 9 inhibitor.

Figure 3. Distribution of categories of percent LDL‐C reduction in patients with HeFH and patients with HoFH receiving PCSK9is at the different time points during treatment.

Data are reported as percentage of patients per each time point according to lipid‐lowering response to PCSK9i. Categories defined as percent LDL‐C reduction from baseline according to 4 groups: <15%, 15% to 30%, 30% to 50%, and >50%. These categories are represented in orange, green, blue, and violet, respectively, and are reported for each time point up to 24 months. Data in patients with HeFH (A) and in patients with HoFH (B). HeFH indicates heterozygous familial hypercholesterolemia; HoFH, homozygous familial hypercholesterolemia; and LDL‐C, low‐density cholesterol.