Abstract Background VICTORION-1 PREVENT (V-1P) is an ongoing randomized clinical trial comparing inclisiran sodium 300mg every six months with placebo for primary prevention in patients with high cardiovascular (CV) risk. Purpose We evaluated the generalizability of V-1P trial enrollment criteria to the US population to understand the demographic and CV health characteristics of the trial target population. Methods We included data from the National Health and Nutrition Examination Survey (N=25,531, 2015-March 2020), a nationally representative sample of the US population. Enrollment criteria similar to V-1P were applied. Nonpregnant adults 40-79 years with low-density lipoprotein cholesterol (LDL-C) of 70-189 mg/dL were included. 10-year risk for CV disease was determined using the American Heart Association race-free 10-year PREVENT risk equations. Individuals with 10-year risk >20% or 7.5%-19.9% with two risk enhancing factors at baseline were included. Risk enhancing factors included elevated high sensitivity C-reactive protein (≥2 mg/L), inflammatory arthritis, estimated glomerular filtration rate <60 ml/min/1.73 m2, metabolic syndrome, or early family history of CV disease. Patients with history of atherosclerotic CV disease or liver disease were excluded. Estimates of demographics and health characteristics were nationally representative using survey weights. Results Among US adults, 21,576,506 (standard error [SE]: ±1,258,255) meet eligibility criteria for V-1P (weighted estimate). This represents 8.8% of all US adults or 15.1% of US adults 30-79 years. The V-1P eligible population had a mean age of 65.3 years (SE: ±0.5 years), and 55.0% (SE: ±2.5%) were female. Compared with the US adult population (≥18 years), V-1P eligible population had a higher mean body mass index (32.6 ± 0.3 kg/m2 vs 29.5 ± 0.2 kg/m2) and higher rates of obesity (61.0% ± 2.1% vs 40.0% ± 1.1%) (Table). V-1P eligible population also had higher mean systolic blood pressure (133.9 ± 1.0 mmHg vs 121.7 ± 0.3 mmHg), similar mean diastolic blood pressure (72.6 ± 0.8 mmHg vs 71.8 ± 0.2 mmHg), and higher rates of hypertension (85.8% ± 2.0% vs 45.9% ± 1.1%). Mean hemoglobin A1c percent (6.3 ± 0.1 vs 5.7 ± 0.02), fasting blood sugar (127.7 ± 1.9 mg/dL vs 109.2 ± 0.6 mg/dL), and diabetes rates (39.7% ± 2.6% vs 13.1% ± 0.7%) were higher in the V-1P eligible population. Mean low-density lipoprotein cholesterol (115.8 ± 1.5 mg/dL vs 110.2 ± 0.8 mg/dL) and fasting triglycerides (137.6 ± 5.0 mg/dL vs 110.4 ± 1.7 mg/dL) were higher, while mean high-density lipoprotein cholesterol was lower (49.9 ± 0.8 mg/dL vs 54.8 ± 0.4 mg/dL). The distribution of key CV risk factors is shown in the Figure. Conclusion V-1P enrollment criteria apply to many patients. These patients have significant cardiometabolic risk factor burden, and effective preventive therapies could have substantial health impact.