Abstract Body (Do not enter title and authors here): Introduction: Inclisiran is a small interfering RNA drug which inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). Inclisiran was recently approved for the treatment of hypercholesterolemia and durably lowers LDL levels by around 50% with injections once every six months based on the results of large, randomized controlled trials. However, no nationwide studies have evaluated the use or effectiveness of Inclisiran in routine clinical practice.
Goals/Aims: To characterize the use and effectiveness of Inclisiran in routine clinical practice in a large nationwide cohort.
Methods/Approach: We used the Truveta healthcare database, a large nationwide database of electronic health records, to study patients who were administered Inclisiran up to September 2023. Patient demographic characteristics and lipid levels before and after treatment were summarized. Means and 95% confidence intervals were estimated using t-tests.
Results/Data: A total of 5,256 patients (median age 71, first quartile 65, third quartile 76) were prescribed Inclisiran, of whom 2,919 (55.5%) were Female. In terms of race, most of the patients identified as White (81.0%), and a smaller proportion as African American (7.3%), Asian (2.1%), or American Indian/Alaska Native (0.5%); 7.3% of patients identified as more than one race or did not provide race data. Mean LDL and HDL levels (mg/dL) before Inclisiran were 125 (95% CI 123-127) and 51 (95% CI 51-52) respectively and after Inclisiran were 88 (95% CI 85-90) and 50 (95% CI 49-51) respectively. The mean difference in LDL after treatment was -39 (95% CI -42 to -37) mg/Dl for a mean percent change of -22% (95% CI -25% to -19%). Effects of Inclisiran on LDL levels are shown in Figure 1. At the conference, we will compare effects of Inclisiran to those of Alirocumab and Evolocumab (two older monoclonal antibodies against PCSK9) using a propensity score overlap weighting design.
Conclusions: In a large cohort of patients administered Inclisiran in routine clinical practice, Inclisiran use was associated with substantial decreases in LDL levels, but those decreases were nonetheless smaller than the effects seen in randomized controlled trials of the drug.