Lipids & metabolic liver disease
Safety and Efficacy of the Novel RNA Interference Therapies for Hypertriglyceridemia and Mixed Hyperlipidemia Management: A Systematic Review and Meta-analysis
Authors' conclusion
The newer RNA interference (RNAi) therapies appear safe and have excellent TG-lowering efficacy in patients with HTG and MHL.
Study context
- Population
- Patients with hypertriglyceridemia (HTG) or mixed hyperlipidemia
- Participants
- 334 patients6 randomized controlled trials (RCTs)
- Comparison
- Olezarsen, plozasiran or zodasiran vs placebo
- Outcome
- Safety profile of the drugs
Methodological detailsplacebo-controlled RCTs
- Placebo-controlled RCTs
Pooled result
As reported in the abstract
Safety profile
- Olezarsen, plozasiran and zodasiran well tolerated; no higher risk of serious adverse events or injection-site reactions
- Plozasiran increased alanine aminotransferase and HbA1c more than placebo after 24 weeks; difference insignificant at 48 weeks
- Plozasiran and zodasiran had little effect on hyperglycemia worsening
- Olezarsen increased likelihood of mild platelet count decreases without clinical harm
Further pooled results
| Outcome | Olezarsen | Plozasiran | Zodasiran |
|---|---|---|---|
| Percent change from baseline in TG, highest doses · longest trial follow-upTG lowered by these percentages of baseline levels | 55.2% | 50.57% | 51.2% |
Other lipids
- All three drugs decreased non-HDL-C and remnant cholesterol
- Olezarsen and plozasiran lowered ApoC-III and increased HDL-C; zodasiran reduced HDL-C
- Zodasiran decreased LDL-C; olezarsen and plozasiran had no effect on LDL-C
- Plozasiran and zodasiran lowered apolipoprotein B, olezarsen did not
Original publication
Safety and Efficacy of the Novel RNA Interference Therapies for Hypertriglyceridemia and Mixed Hyperlipidemia Management: A Systematic Review and Meta-analysis. Endocr Pract. Published 6 September 2024. doi:10.
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