permit monotherapy use, in addition to diet and exercise, for adults with hypercholesterolemia more broadly. For veterans, inclisiran’s defining clinical advantage may be its dosing schedule: an initial subcutaneous injection, a second dose at three months, and then just twice yearly thereafter, always administered by a healthcare provider. In the VA, this provider-administered schedule removes the burden of daily pill-taking or frequent self- injection, directly addressing one of the most common causes of treatment failure: non-adherence. In three pivotal randomized, placebo-controlled trials enrolling 3,457 adults with HeFH or clinical ASCVD, inclisiran produced LDL-C reductions of 40% to 51% at 17 months, sustained and consistent reductions with an excellent tolerability profile.9 For older veterans, who often manage multiple chronic conditions and complex medication regimens, a therapy requiring only two clinic visits per year for cholesterol management represents a meaningful simplification. Further, its lack of significant drug-drug interactions elimi- nates concern about co-administration with the multiple drugs many veterans already receive, while its subcutane- ous administration by VA staff ensures patients receive critical cholesterol-lowering treatment. A New Era for Veterans With FH VA research is helping change the massive under- diagnosis and undertreat- ment of FH, using the unparalleled scale of the Million Veteran Program to identify affected veter- ans and return actionable results. As the treatment landscape expands, with high-intensity statins, ezet- imibe, and now multiple PCSK9 inhibitor options including the twice-yearly inclisiran, clinicians have the tools to bring even severely elevated LDL-C under control. For veterans carrying a genetic burden of elevated cholesterol, these advances represent a genuine oppor- tunity for longer, healthier lives. 1Saadatagah S, Jose M, Dikilitas O, et al. Genetic basis of hypercholes- terolemia in adults. NPJ Genom Med. 2021 Apr 14;6(1):28. doi: 10.1038/ s41525-021-00190-z. Erratum in: NPJ Genom Med. 2021 Jun 29;6(1):56. doi: 10.1038/s41525-021-00222-8. PMID: 33854068; PMCID: PMC8046820. 2Nguyen XT, Ho YL, Li Y, Song RJ, Leung KH, Rahman SU, Orkaby AR, Vassy JL, Gagnon DR, Cho K, Gaziano JM, Wilson PWF. Serum Cholesterol and Impact of Age on Coronary Heart Disease Death in More Than 4 Million Veterans. J Am Heart Assoc. 2023 Nov 7;12(21):e030496. doi: 10.1161/JAHA.123.030496. Epub 2023 Oct 27. PMID: 37889207; PMCID: PMC10727410. 3VA/DoD Clinical Practice Guideline on Lipid Management for Cardio- vascular Disease Risk Reduction, 2025. https://www.healthquality.va.gov/ HEALTHQUALITY/guidelines/CD/lipids/Lipids-CPG_2025-Guideline_ final_20260106.pdf 4Ahmad Z, Agarwala A, Cuchel M, et al. Update on familial hypercholes- terolemia: An expert clinical consensus from the National Lipid Associa- tion. Journal of Clinical Lipidology. 2026. DOI: 10.1016/j.jacl.2026.01.011 5Vassy JL, Brunette CA, Yi T, et al. Design and pilot results from the Million Veteran Program Return Of Actionable Results (MVP-ROAR) Study. American Heart Journal. 2024;276:99-109. https://doi.org/10.1016/j. ahj.2024.04.021 6Vassy JL, Brunette CA, Yi T, et al. Opportunistic genomic screening for familial hypercholesterolemia to improve low-density lipoprotein cholesterol: A randomized clinical trial. JAMA Network Open. 2026;9(1):e2549664. doi:10.1001/jamanetworkopen.2025.49664 7Djoussé L. Quality improvement program to reduce LDL-C among veter- ans with cardiovascular disease. Presented at: American Heart Associa- tion Scientific Sessions 2025; November 7-10, 2025; New Orleans, LA. 8Cegla J, Walji S, Barton L, Neuwirth C, Thompson GR. Treatment of homozygous familial hypercholesterolemia. JACC: Advances. 2025;4(5). https://doi.org/10.1016/j.jacadv.2025. The Dutch Lipid Clinic Network Criteria Criteria Points Family History First-degree relative with premature coronary and/or vascular disease or LDL-C >95th percentile for age and sex 1 Children aged <18 years with LDL-C >95th percentile for age and sex or first-degree relative with tendon xanthomas and/or arcus cornealis 2 Personal history of premature ASCVD Coronary heart disease 2 Cerebral or peripheral vascular disease 1 Physical Examination Tendon xanthomas 6 Arcus cornealis at age <45 years 4 Plasma levels of LDL-C LDL-C >325 mg/dL 8 LDL-C 251-325 mg/dL 5 LDL-C 191-250 mg/dL 3 LDL-C 155-190 mg/dL 1 Molecular genetic testing Pathogenic variants in LDL-R, APOB, or PCSK9 8 *Choose the highest score within each diagnostic group and use the sum of all groups to classify: FH is considered present if a total score is >8 points; probable FH if score is 6 to 8 points; possible FH if score is 3 to 5 points; if the score is 0 to 2 points, FH is unlikely. Source: VA/DoD Clinical Practice Guideline 3 8
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