Estimated impact of inclisiran treatment on hyperlipidemia prevalence and cardiovascular disease events in NHANES dataset

Abstract Background Inclisiran, administered subcutaneously every 6 months, will result in the reduction of LDL-cholesterol levels of approximately 50%. We estimated the eligibility of the US population for Inclisiran treatment and its impact on blood lipids and CVD events. Methods We applied ORION trial eligibility criteria to US adults aged ≥ 18 years in the US NHANES 1999-2018 to estimate the US eligible population. Blood lipid alterations in ORION 10 were applied to estimate the impact on LDL-C levels and hyperlipidemia prevalence in the ASCVD population sample. We also used the Framingham CVD risk scores to estimate 10-year CVD risks in the ASCVD high-risk population sample based on ORION 11. The difference in estimated risks with and without Inclisiran administration, multiplied by the eligible population from NHANES data, represented the potentially preventable CVD events. Results We identified 651 ASCVD persons (projected to 5.55 million) who fit ORION 10 trial eligibility criteria and 359 ASCVD high-risk persons (projected to 2.53 million) who fit ORION 11 trial eligibility criteria for our analysis. We then analyzed the changes in these populations after Inclisiran treatment. Firstly, we estimated that approximately 3.9 million (72.8%) individuals would experience ≥50% LDL-C reductions. Secondly, we estimated that among the ASCVD patients, 5.07 million (91.3%) with elevated LDL-C, 0.25 million (22.8%) with reduced HDL-C, 1.24 million (95.2%) with elevated TC, and 0.65 million (32.4%) with elevated TG would potentially achieve a more reasonable blood lipid level. Finally, among those without CVD, the estimated 10-year CVD risks were 19% before and 13.8% after Inclisiran treatment, reflecting a 5.2% absolute (and 27.4% relative) reduction in risk translating to potentially 130,000 preventable CVD events over 10 years. Conclusion Inclisiran treatment in eligible US adults may substantially reduce hyperlipidemia prevalence and CVD events.core graphics