- Sniderman AD, Dufresne L, Pencina KM, Bilgic S, Thanassoulis G, Pencina MJ. Discordance among apoB, non-high-density lipoprotein cholesterol, and triglycerides: implications for cardiovascular prevention. Eur Heart J 2024;45:2410–8. https://doi. org/10.1093/eurheartj/ehae258. High variability of apoB at individual levels of LDL-C, non-HDL-C, and triglycerides coupled with meaningful differences in 10-year ASCVD rates and significant residual information contained in apoB for prediction of new-onset ASCVD events demonstrate that LDL-C, non- HDL-C, and triglycerides are not adequate proxies for apoB in clinical care. Whether targeting apoB instead of LDL cholesterol will provide better information in intervention trials needs to be seen.
- Schubert J, Leosdottir M, Lindahl B et al. Intensive early and sustained lowering of non-high-density lipoprotein cholesterol after myocardial infarction and prognosis: the SWEDEHEART registry. Eur Heart J 2024;45:4204–15. The lowest achieved levels both at 2 months and at 1 year of non–HDL-C were associated with better outcome. The lowest risk was observed when target was achieved within 2 months of MI and sustained thereafter. These findings challenge the current stepwise approach for cholesterol lowering after MI, which inevitably results in delaying goal attainment and possible harm.
- Klug EQ, Llerena S, Burgess LJ et al. Efficacy and safety of lerodalcibep in patients with or at high risk of cardiovascular disease: a randomized clinical trial. JAMA Cardiol 2024; 9:800–7. https://doi.org/10.1001/jamacardio. 2024.1659. Early DOAC initiation within 4 days after Lerodalcibep is an adnectin with an anti-PCSK9 binding domain that has a high affinity for PCSK9, is administered subcutaneously monthly at a dose of 300 mg, and does not require refrigeration. The results support longterm use of lerodalcibep for LDL-C treatment for patients with CVD or who are at very high or high risk of CVD and are unable to achieve adequate LDL-C reduction while receiving maximal tolerated statins alone.
- Gaudet D, Greber-Platzer S, Reeskamp LF et al. Evinacumab in homozygous familial hypercholesterolaemia: long-term safety and efficacy. Eur Heart J 2024;45:2422–34. Evinacumab, a monoclonal antibody targeting Angiopoietin-like 3 inhibits the activity of lipoprotein lipase and endothelial lipaseIn this large cohort of patients with HoFH, evinacumab was generally well tolerated and markedly decreased LDL-C irrespective of age and sex. Moreover, the efficacy and safety of evinacumab was sustained over the long term.
- Rosenson RS, Gaudet D, Hegele RA et al. Zodasiran, an RNAi therapeutic targeting ANGPTL3, for mixed hyperlipidemia. N Engl J Med 2024;391:913–25. Angiopoietin-like 3 (ANGPTL3) inhibits lipoprotein and endothelial lipases and hepatic uptake of triglyceride-rich lipoprotein remnants. Zodasiran is an RNA interference therapy targeting expression of ANGPTL3 in the liver. In patients with mixed hyperlipidemia, zodasiran was associated with significant decreases in triglyceride levels at 24 weeks.
- Ballantyne CM, Vasas S, Azizad M, et al. Plozasiran, an RNA interference agent targeting APOC3, for mixed hyperlipidemia. N Engl J Med 2024; 391:899–912. https://doi. org/10.1056/NEJMoa2404143. Persons with mixed hyperlipidemia are at risk for atherosclerotic cardiovascular disease due to an elevated non–high-density lipoprotein (HDL) cholesterol level, which is driven by remnant cholesterol in triglyceride-rich lipoproteins. The metabolism and clearance of triglyceride-rich lipoproteins are downregulated through apolipoprotein C3 (APOC3)– mediated inhibition of lipoprotein lipase. In this phase 2b, double-blind, randomized, placebocontrolled trial the safety and efficacy of plozasiran, a hepatocyte-targeted APOC3 small interfering RNA,was evaluated in patients with mixed hyperlipidemia. Plozasiran, as compared with placebo, significantly reduced triglyceride levels at 24 weeks. A clinical outcomes trial is warranted.
- Gibson CM, Duffy D, Korjian S, et al. Apolipoprotein A1 infusions and cardiovascular outcomes after acute myocardial infarction. N Engl J Med 2024;390:1560–71. https://doi.org/10.1056/NEJMoa2400969. CSL112 is a human apolipoprotein A1 (the main protein in high-density lipoprotein) that can be administered intravenously, resulting in a doubling of apolipoprotein A1 levels and a four- fold increase in cholesterol efflux capacity. Among patients with acute myocardial infarction, multivessel coronary artery disease, and additional cardiovascular risk factors, four weekly infusions of CSL112 did not result in a lower risk of myocardial infarction, stroke, or death from cardiovascular causes than placebo through 90 days.
- Arnold N, Blaum C, Goßling A et al. C-reactive protein modifies lipoprotein(a)-related risk for coronary heart disease: the BiomarCaRE project. Eur Heart J 2024;45:1043–54. https://doi.org/10.1093/eurheartj/ehad867. While among coronary heart disease (CHD) -free individuals Lp(a) was significantly associated with incident CHD regardless of hsCRP, in participants with CHD at baseline, Lp(a) was related to recurrent CHD events only in those with residual inflammatory risk. These findings might guide adequate selection of highrisk patients for forthcoming Lp(a)-targeting compounds.
- Nissen SE, Wang Q, Nicholls SJ et al. Zerlasiran—a small-interfering RNA targeting lipoprotein(a): a phase 2 randomized clinical trial. JAMA 2024;332:1992–2002.10.1001 jama.2024.21957. Elevated lipoprotein(a) increases the risk of atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis. Zerlasiran, a smallinterfering RNA targeting hepatic synthesis of apolipoprotein(a), was well-tolerated and reduced time-averaged lipoprotein(a) concentration by more than 80% during 36 weeks of treatment in patients with ASCVD.
- Nicholls SJ, Ni W, Rhodes GM, Nissen SE, Navar AM, Michael LF, et al. Oral muvalaplin for lowering of lipoprotein(a): a randomized clinical trial. JAMA 2024;333:222–31. 10. 1001/jama.2024.24017 . Muvalaplin, an oral agent, inhibits lipoprotein(a) formation. In this trial muvalaplin reduced lipoprotein(a) measured using intact lipoprotein(a) and apolipoprotein(a)-based assays and was well tolerated. The effect of muvalaplin on cardiovascular events requires further investigation.
Accedi per leggere tutto l'articolo
Inserisci i dati del tuo account su Cardiotalk per accedere e leggere tutto il contenuto dell'articolo.
Se non hai un account, clicca sul pulsante registrati e verrai reindirizzato al portale Cardiotalk per la registrazione.
