Cardiovascular Medicine 2025: Landmark Dyslipidaemia Studies Redefine Lipid Management
Turkey: The year 2025 marked a turning point in dyslipidaemia research, with major advances reshaping how lipid-related cardiovascular risk is understood and managed. In a viewpoint published in the European Heart Journal, Lale Tokgozoglu from the Department of Cardiology, Hacettepe University Faculty of Medicine, Ankara, Turkey, and colleagues highlighted the 10 most influential studies that defined the field over the past year. Together, these papers reinforce the principle of early, intensive lipid lowering while introducing novel therapeutic strategies targeting LDL cholesterol, triglyceride-rich lipoproteins, and lipoprotein(a) [Lp(a)].
Key advances and takeaways from 2025 include:
- Updated guidelines and lower LDL-C goals: The updated European Society of Cardiology/European Atherosclerosis Society guidelines emphasized earlier and more aggressive LDL-C reduction, supported by growing evidence that “lower is better” across the cardiovascular risk spectrum.
- PCSK9 inhibition beyond traditional boundaries: The VESALIUS-CV trial provided definitive evidence that evolocumab reduces major adverse cardiovascular events (MACE) in high-risk patients without prior myocardial infarction or stroke. LDL-C was reduced by over 50%, with significant reductions in myocardial infarction, revascularization, cardiovascular death, and even all-cause mortality, challenging the rigid distinction between primary and secondary prevention.
- Oral PCSK9 inhibition becomes reality: Enlicitide, the first oral PCSK9 inhibitor, demonstrated robust LDL-C reductions of up to 60% in patients with heterozygous familial hypercholesterolaemia. Its efficacy, tolerability, and convenience may expand access to intensive lipid lowering once outcome data become available.
- New insights into PCSK9 biology: Mechanistic studies showed that LDL-bound PCSK9 is cleared more slowly than free PCSK9, with hepatic heparan sulfate proteoglycans playing a role. These findings may help explain variability in response to PCSK9-targeted therapies and influence future drug development.
- Gene-editing therapy enters the lipid arena: First-in-human data with CRISPR–Cas9 therapy targeting ANGPTL3 demonstrated sustained reductions in LDL-C and triglycerides after a single infusion. While early and limited in size, this study provided proof of concept for one-time genetic therapies in dyslipidaemia.
- Lifetime lipid exposure matters: Analysis from the CARDIA cohort showed that cumulative exposure to apoB, LDL particles, and triglyceride-rich lipoproteins from young adulthood strongly predicts later atherosclerotic cardiovascular disease. These findings underscore the importance of early prevention, not just midlife intervention.
- CETP inhibition revisited: Obicetrapib, a selective CETP inhibitor, achieved meaningful reductions in LDL-C, apoB, and Lp(a) on top of maximal background therapy, without safety concerns. This revived interest in CETP inhibition as an adjunctive strategy.
- Reassuring statin data in early pregnancy: Large registry data and an updated meta-analysis showed no significant increase in major or cardiac congenital malformations with inadvertent first-trimester statin exposure, providing reassurance to women and clinicians while maintaining caution against routine use during pregnancy.
- Targeting triglycerides and pancreatitis risk: Olezarsen, an antisense oligonucleotide targeting apoC-III, produced substantial and sustained triglyceride reductions in severe hypertriglyceridaemia and was associated with fewer pancreatitis events, highlighting apoC-III as a key therapeutic target.
- Lp(a) moves to the forefront: Multiple studies confirmed that elevated Lp(a) confers continuous cardiovascular risk. High-intensity LDL-C lowering appeared to mitigate this risk, and data from Sweden showed that first-degree relatives of individuals with high Lp(a) levels face increased MACE risk, supporting cascade screening.
In summary, the top dyslipidaemia papers of 2025 collectively reinforce a shift toward earlier, stronger, and more personalized lipid management. With innovations ranging from oral PCSK9 inhibitors to gene-editing therapies and growing recognition of lifetime lipid exposure and inherited risk, the field is rapidly evolving toward more effective cardiovascular prevention strategies.
Reference:
Tokgozoglu, L., Catapano, A., & Laufs, U. (2026). The year in Cardiovascular Medicine 2025: The top 10 papers in dyslipidaemias. European Heart Journal, 47(4), 401-404. https://doi.org/10.1093/eurheartj/ehaf1045
