👤 Farhana Amanullah

Hypertriglyceridemia (HTG) increases cardiovascular and pancreatitis risk. Antisense oligonucleotide (ASO) therapies like volanesorsen and olezarsen target ApoC-III mRNA to reduce ApoC-III, enhancing lipoprotein lipase activity and lowering triglycerides (TGs). This meta-analysis evaluates the efficacy and safety of these ASOs in severe HTG. A systematic review (PROSPERO: CRD42024577110) was conducted following PRISMA, sourcing studies from PubMed, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov until July 2024. Randomized controlled trials (RCTs) involving severe HTG (≥200 mg/dL) treated with volanesorsen or olezarsen vs. placebo were included. Data were synthesized using a random effects model in RevMan 5.4, and bias was assessed with the Cochrane tool. Of 31 identified articles, 9 RCTs (341 patients treated with ASOs, 209 controls) were included. ASOs significantly reduced TG levels [mean difference (MD): -53.72; 95% confidence interval (CI): -77.04 to -30.40; p<0.00001]. Reductions were also seen in very low-density lipoprotein cholesterol (MD: -55.76; p<0.00001), ApoC-III (MD: -74.78; p<0.00001), and APOB48 (MD: -69.45; p<0.00001). Olezarsen uniquely reduced APOB (MD: -15.60; p<0.00001). Non-high-density lipoprotein cholesterol (HDL-C) decreased (MD: -23.25; p<0.00001), while HDL-C increased (MD: +42.14; p<0.00001). Volanesorsen was linked to higher low-density lipoprotein-cholesterol (MD: +62.74; p=0.004). For safety, local injection reactions, thrombocytopenia, and nausea were more common with volanesorsen. Acute pancreatitis occurred only in the placebo group (relative risk: 0.15; p=0.0004), indicating ASO protection. This meta-analysis confirms that ASOs effectively lower TGs and improve lipid profiles in severe HTG. Show less

Lipoprotein(a) (Lp(a)) is a proatherogenic lipoprotein associated with increased cardiovascular risk and is minimally responsive to statins or lifestyle changes. While Lp(a) is linked to adverse cardiovascular events, its role in predicting repeat revascularization after percutaneous coronary intervention (PCI) remains unclear. This review evaluates the relationship between Lp(a) levels and coronary revascularization outcomes. A systematic review and meta-analysis of studies from MEDLINE and EMBASE through June 18, 2025, evaluated the association between elevated Lp(a) and revascularization outcomes post-PCI. Random-effects models using the DerSimonian-Laird method were used to pool odds (ORs) and hazard ratios (HRs). Heterogeneity was assessed using the I Twenty studies were included in the systematic review, of which eighteen were included in the meta-analysis. Elevated Lp(a) levels were associated with a higher risk of any repeat revascularization, with pooled OR 1.33 (95% CI: 1.17-1.52) and HR 1.15 (95% CI: 1.05-1.25). High Lp(a) was also linked to increased risk of target vessel revascularization (TVR) (OR 1.42; 95% CI: 1.12-1.81). A non-significant trend towards increased target lesion revascularization (TLR) was observed (OR 1.25; 95% CI: 0.96-1.64). Elevated Lp(a) levels were associated with a higher risk of repeat revascularization and TVR, with a non-significant trend towards increased TLR. Further studies are warranted to confirm these findings and explore the potential benefit of Lp(a)-lowering strategies. Show less