*Real-World Experience with Inclisiran at a Large Academic Lipid Clinic

Background/Synopsis

Inclisiran is an siRNA that targets PCSK9 and lowers LDL-C by approximately 50%. Inclisiran is unique among lipid-lowering therapies (LLTs) available for LDL-C reduction as it is administered via subcutaneous injection by a healthcare professional every 6 months. Real-world data examining inclisiran use in US clinical practice are limited.

Objective/Purpose

Examine patient characteristics and LDL-C reduction during the initial two-year experience with inclisiran at a large academic lipid clinic.

Methods

We performed a retrospective chart review of 60 patients at a large academic lipid clinic who were prescribed inclisiran between March 2022 to November 2023 and had follow-up LDL-C measurements taken ≥ 30 days after initiating treatment as part of routine care. Background LLT was extracted from the medical record and reflects treatment at time of inclisiran initiation. Absolute and percent LDL-C reduction was examined during follow-up. LDL-C reduction from baseline was assessed within group using a paired samples t-test with two-sided p < 0.05 considered significant.

Results

Among 60 patients, mean (± SD) age was 71 ± 9.2 years (52% women, 90% White, 2% Hispanic/Latino, 8% Asian), 87% with history of ASCVD, 70% with statin intolerance, 20% with HeFH, and 50% on background statin therapy (Table). During the 4.4 ± 2.8 months of follow-up from first dose of inclisiran to first LDL-C measurement, 2 patients had received three doses of inclisiran, 34 patients had received two doses, and 24 patients had received one dose. LDL-C decreased from 107 ± 47 mg/dL at baseline to 67 ± 42 mg/dL at first follow up (-37%, p < 0.001). Excluding patients that switched from a PCSK9i monoclonal antibody (mAb) within approximately one month prior to starting inclisiran (n=12) or patients on no background LLT at time of inclisiran initiation (n=9), patients saw a decrease in mean LDL-C from 102 ± 42 mg/dL at baseline to 54 ± 40 mg/dL at first follow-up ((n=39) -47%, p <0.001) (Figure).

Conclusions

Patients that remained on background lipid-lowering therapy and did not switch from PCSK9i mAb to inclisiran observed LDL-C reductions of approximately 50%, consistent with inclisiran clinical trials. Additional real-world data examining the impact of inclisiran on LDL-C are needed, across multiple centers and among patients on various background LLT regimens.