Estimating the Effect of Inclisiran on Dyslipidemia and Primary Prevention of Cardiovascular Disease: The NHANES 1999-2018 Study

Abstract

Background Dyslipidemia has been delineated as independent predictors of cardiovascular disease (CVD). Inclisiran, an innovative small interfering RNA (siRNA) agent, is anticipated to engender a notable reduction of approximately 50% in low-density lipoprotein cholesterol (LDL-C) levels. Given its transformative impact, we scrutinized the eligibility of US population for inclisiran treatment and evaluated its potential effects on dyslipidemia and the primary prevention of CVD. Methods We applied eligibility criteria from the ORION 10 and 11 trials to the 1999–2018 National Health and Nutrition Examination Survey dataset to estimate the eligible population size for atherosclerotic cardiovascular disease (ASCVD) and ASCVD-risk equivalents. Utilizing lipid reduction data from the ORION 10, we predicted the impact of inclisiran on LDL-C levels and dyslipidemia prevalence among ASCVD patients. Similarly, leveraging the ORION 11's lipid reduction data, we forecasted inclisiran's effect on 10-year CVD risk change and preventable CVD events in the ASCVD-risk equivalents population, employing the Framingham CVD Risk Score. Results We identified 613 ASCVD patients (5.28 million) and 377 ASCVD-risk equivalents (2.63 million) who met the eligibility criteria of the ORION 10 and 11. Among ASCVD population, 3.71 million (70.3%) would achieve ≥ 50% LDL-C reduction post-treatment. Furthermore, 4.86 million (91.9%) with high LDL-C, 0.22 million (4.2%) with low high-density lipoprotein cholesterol, 1.19 million (22.5%) with high total cholesterol, and 0.5 million (9.5%) with high triglycerides would attain target lipid profiles. For ASCVD-risk equivalents population, the estimated 10-year CVD risk would decrease from 25.2–17.6% (7.6% absolute, 30.2% relative) post-inclisiran treatment, potentially preventing 199,878 CVD events over a decade, including 136,217 coronary heart disease cases, 37,024 strokes, and 23,619 heart failures. Conclusions Inclisiran holds the potential to substantially diminish the prevalence of dyslipidemia and mitigate the occurrence of nearly 200 thousand CVD events in eligible US adults.