Cardiovascular Medicine 2025: Landmark Dyslipidaemia Studies Redefine Lipid Management

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