Lipid-lowering therapy with inclisiran in the real-world setting: Initial data from a national health care service.

Background: Inclisiran, a small-interfering RNA enabling long-term inhibition of proprotein convertase subtilisin kexin type 9 (PCSK9) synthesis, demonstrates a good safety and efficacy profile in clinical trials. Real-world data on the potential to attain lipid-goals and reduce treatment gaps are lacking.

Objectives: To investigate the implementation of inclisiran in real-world clinical setting.

Methods: Data from a nationwide healthcare organization on patients initiating inclisiran between 3/2022-11/2023. Patients' characteristics, lipid-lowering therapies, post-treatment reduction in low-density lipoprotein cholesterol (LDL-C), and attainment of treatment goals were evaluated.

Results: Inclisiran was initiated by 503 patients (57% women; mean age 66±11 years). Cardiovascular disease was present in 54%, and peak LDL-C levels >190 mg/dL documented in 64%. Prior exposure to PCSK9 monoclonal antibodies was evident in 28%. Lipid profile >2 months after filling first prescription, was available in 397 patients (347 with ≥2 injections). In patients treated by inclisiran only (n = 254), median LDL-C reduction from peak levels was 57% (interquartile range [IQR], 48%-67%), and from pre-injection levels 40% (19%-54%). In those with concomitant lipid-lowering therapies (n = 143), median LDL-C reduction from peak levels was 66% (IQR, 55%-73%), and from pre-injection levels 46% (23%-59%). LDL-C < 70 mg/dL was attained by 39% and LDL-C < 55 mg/dL by 21.9%. Of those treated with concomitant statin therapy, 38% attained LDL-C < 55 mg/dL. Overall, 6.5% discontinued inclisiran therapy after initial injection.

Conclusions: In real-world practice, inclisiran showed good efficacy in reducing LDL-C with high interindividual variability. However, attainment rates of lipid goals were suboptimal due to limited use of combination lipid-lowering therapy and high rates of severe hypercholesterolemia in our patient population cohort.