1. Bohula EA, Marston NA, Bhatia AK. Evolocumab in patients without a previous myocardial infarction or stroke. N Engl J Med, doi.org/10.1056/NEJMoa2514428. PCSK9 inhibition with evolocumab led to a lower risk of first cardiovascular events than placebo among patients with atherosclerosis or diabetes and without a previous myocardial infarction or stroke.
2. Ballantyne CM, Gellis L, Tardif JC, et al. Efficacy and safety of oral PCSK9 inhibitor enlicitide in adults with heterozygous familial hypercholesterolemia: a randomized clinical trial. JAMA, https://doi.org/ 10.1001/ jama.2025.20620. Among adults with heterozygous familial hypercholesterolemia, treatment with enlicitide was well tolerated and significantly reduced levels of LDL-C, apolipoprotein B, non–HDL-C, and lipoprotein(a).
3. Pacheco-Velázquez SC, Oleaga C, et al. LDL-bound PCSK9 has a slower clearance kinetic and higher use for HSPGs than free- PCSK9-brief report. Arterioscler Thromb Vasc Biol 2025;45:1565–73. https://doi. org/10.1161/ATVBAHA.124.322334. Hepatic heparan sulfate proteoglycans (HSPGs) accelerate the clearance of PCSK9 (proprotein convertase subtilisin/kexin type 9). The clearance rate of plasma LDL-bound PCSK9 is slower than the clearance rate of its free form. The HSPG syndecan-1 modestly contributes to PCSK9 clearance through an LDLR-independent pathway.
4. Laffin LJ, Nicholls SJ, Scott RS, et al. Phase 1 trial of CRISPR-cas9 gene editing targeting ANGPTL3. N Engl J Med 2025; 393:2119–30. Angiopoietin-like protein 3 (ANGPTL3) inhibits lipoprotein and endothelial lipases. ANGPTL3 loss-of-function genetic variants are associated with decreased levels of low-density lipoprotein cholesterol and triglycerides and a decreased lifetime risk of atherosclerotic cardiovascular disease. Editing of ANGPTL3 was associated with few adverse events and resulted in reductions from baseline in ANGPTL3 levels.
5. Zheutlin AR, Handoo F, Luebbe S, et al. Cumulative exposure to atherogenic lipoprotein particles in young adults and subsequent incident atherosclerotic cardiovascular disease. Eur Heart J 2025; 46:4302–12. Cumulative exposure to atherogenic lipid particles in young adulthood increases the risk for incident atherosclerotic cardiovascular disease later in life. Apolipoprotein B concentration <75 mg/dL may represent a goal to maintain low risk in young adults.
6. Nicholls SJ, Nelson AJ, Ditmarsch M, Kastelein JJP, Ballantyne CM, Ray KK, et al. Safety and efficacy of obicetrapib in patients at high cardiovascular risk. N Engl J Med 2025;393: 51–61. Among patients with atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia who were receiving maximum tolerated doses of lipidlowering therapy and were at high risk for cardiovascular events, obicetrapib reduced LDL cholesterol levels by 29.9%.
7. Christensen JJ, Holven KB, Bogsrud MP, et al. Statin use in pregnancy and risk of congenital malformations: a Norwegian nationwide study. Eur Heart J, https://doi. org/10.1093/eurheartj/ ehaf592. In this large, nationwide study and updated meta-analysis, no significant association was observed between first-trimester exposure to statins or other lipid-modifying agents and congenital malformations. Although limited power may have prevented detection of weak but clinically relevant associations, the findings do not support a strong or independent association between statin exposure in pregnancy and congenital malformations.
8. Marston NA, Bergmark BA, Alexander VJ, et al. Olezarsen for managing severe hypertriglyceridemia and pancreatitis risk. N Engl J Med 2026;394:429-441. doi:10.1056/NEJMoa2512761. Among patients with severe hypertriglyceridemia, treatment with olezarsen led to a significantly greater reduction in the triglyceride level at 6 months and in the incidence of acute pancreatitis than placebo.
9. MacDougall DE, Tybjærg-Hansen A, et al. Lipoprotein(a) and recurrent atherosclerotic cardiovascular events: the US family heart database. Eur Heart J 2025; 46:4762–75. In 273.770 individuals with atherosclerotic cardiovascular disease (ASCVD), higher lipoprotein(a) levels were associated with continuously increasing risk of recurrent ASCVD events regardless of sex and race/ ethnicity that may have been partially mitigated by high impact LDL cholesterollowering therapy.
10. Kindborg G, Eriksson Hogling D, et al. Major cardiovascular events in first degree relatives of individuals with elevated plasma lipoprotein(a): a registrybased cohort study. Eur Heart J, https:// doi.org/10.1093/eurheartj/ehaf677. First-degree relatives of individuals with elevated Lp(a) levels have a higher incidence of MACE. Cascade screening could be a feasible strategy to identify first-degree relatives at heightened risk.
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