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Olezarsen in Hypertriglyceridemia With High Cardiac Risk: A GRADE-Assessed Meta-Analysis of Randomized Trials With
Ahmed Emara1, Ameer Awashra2, Heba Aboeldahab3
1Faculty of Medicine, Al-Azhar University, Cairo, Egypt.
Background:
Hypertriglyceridemia is a widely prevalent disorder of lipid metabolism that increases the risk of cardiovascular disease and pancreatitis, and it often remains difficult to control even with standard treatments. Olezarsen, an antisense oligonucleotide that targets apolipoprotein C-III (ApoC-III), offers a new and promising option for lowering triglyceride levels.
Methods:
A systematic search of PubMed, Scopus, Web of Science, and Cochrane was conducted through September 2025 to identify randomized controlled trials (RCTs) comparing olezarsen with placebo in adults with hypertriglyceridemia at high cardiovascular risk. Dichotomous outcomes were analysed as risk ratios (RRs) and continuous outcomes as percentage mean differences (MDs), both with 95% confidence intervals (CIs).
Results:
Four RCTs (n = 1615 patients) were included. Olezarsen significantly reduced triglycerides (MD -47.71%, 95% CI -56.78 to -38.64, p < 0.0001), non-HDL-C (MD -22.11%, 95% CI -28.48 to -15.75, p < 0.0001), ApoC-III (MD -68.93%, 95% CI -77.54 to -60.31, p < 0.0001), VLDL-C (MD -48.52%, 95% CI -57.16 to -39.87, p < 0.0001), and ApoB (MD -10.67%, 95% CI -16.83 to -4.51, p = 0.0007), while increasing HDL-C (MD 35.13%, 95% CI -27.30 to -42.96, p < 0.0001). LDL-C showed no significant change. The risks of any or serious adverse events were comparable to placebo. Olezarsen was associated with fewer acute pancreatitis events (p = 0.035) but higher rates of liver enzyme elevations ≥ 3× ULN (p = 0.046).
Conclusions:
Olezarsen demonstrated consistent improvements in triglycerides and other atherogenic lipid parameters with an overall acceptable safety profile. These findings suggest that olezarsen may be a useful adjunct option for patients with persistent hypertriglyceridemia despite standard therapy. Further large-scale and long-term studies are needed to confirm its cardiovascular and safety outcomes.
Insights
Olezarsen effectively lowers triglycerides and atherogenic lipids in patients with hypertriglyceridemia. This antisense oligonucleotide shows a promising safety profile, suggesting it as a valuable treatment option.
Area of Science:
- Cardiovascular Medicine
- Lipid Metabolism
- Pharmacology
Background:
- Hypertriglyceridemia is a prevalent metabolic disorder linked to increased cardiovascular disease and pancreatitis risk.
- Standard treatments for hypertriglyceridemia are often insufficient, necessitating novel therapeutic approaches.
- Olezarsen, an antisense oligonucleotide targeting apolipoprotein C-III (ApoC-III), presents a new therapeutic strategy for managing high triglyceride levels.
Purpose of the Study:
- To evaluate the efficacy and safety of olezarsen in adults with hypertriglyceridemia and high cardiovascular risk.
- To compare olezarsen's effects on lipid parameters and adverse events against placebo using randomized controlled trials (RCTs).
Main Methods:
- A systematic literature search was performed across major databases (PubMed, Scopus, Web of Science, Cochrane) up to September 2025.
- Included studies were RCTs comparing olezarsen with placebo in adults with hypertriglyceridemia and high cardiovascular risk.
- Dichotomous and continuous outcomes were analyzed using risk ratios (RRs) and percentage mean differences (MDs) with 95% confidence intervals (CIs).
Main Results:
- Four RCTs involving 1615 patients demonstrated olezarsen's significant reduction in triglycerides (MD -47.71%), non-HDL-C, ApoC-III, VLDL-C, and ApoB.
- Olezarsen increased HDL-C levels (MD 35.13%) with no significant impact on LDL-C.
- Adverse event rates were comparable to placebo, though olezarsen was associated with fewer pancreatitis events but more liver enzyme elevations.
Conclusions:
- Olezarsen consistently improves triglyceride levels and other atherogenic lipid markers with an acceptable safety profile.
- The findings support olezarsen as a potential adjunctive therapy for persistent hypertriglyceridemia unresponsive to standard treatments.
- Further large-scale, long-term studies are warranted to confirm cardiovascular and safety outcomes.
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