Lipids & metabolic liver disease
Comprehensive evaluation of siRNA therapeutics on Lp(a): A network meta‐analysis
Authors' conclusion
Lp(a)-targeted siRNA agents have shown robust effectiveness in substantially reducing Lp(a) levels, including both percentage and absolute reductions, with moderate improvements in LDL-C and apo(B) concentrations. Non-Lp(a)-targeted siRNA agents also demonstrate modest reductions in Lp(a) levels. The safety profile is generally favourable, but zerlasiran and inclisiran may increase the incidence of injection-site reactions.
Study context
- Population
- Patients with dyslipidaemia in randomized controlled trials (RCTs) of ≥12 weeks' intervention (search to October 24, 2024)
- Participants
- 5,646 patients14 trials
- Comparison
- siRNA drugs lowering Lp(a) (Lp(a)-targeted and non-targeted) vs placebo or other siRNA drugs
- Outcome
- % and absolute reduction in Lp(a), % reduction in LDL-C and apo(B), adverse events and serious adverse events incl. injection-site reactions
Methodological detailsrandom-effects, frequentist approach, Confidence In Network Meta-Analysis (CINeMA) confidence assessment, ROB2 risk of bias
- Random-effects
- Frequentist approach
- CINeMA confidence assessment
- ROB2 risk of bias
Pooled result
As reported in the abstract
Lp(a) reduction
Olpasiran vs PlaceboMD, % (95% CI)
Greatest % reduction in Lp(a); P-score: 0.98
−92.06(−102.43% to −81.69%)
Olpasiran vs PlaceboMD, nmol/L (95% CI)
Greatest absolute reduction in Lp(a); P-score: 0.99
−250.70(−279.89 to −221.50)
- Non-Lp(a)-targeted siRNA (e.g., inclisiran, zodasiran) reduced Lp(a) by approximately
- 15%
Further pooled results
Low-density lipoprotein cholesterol (LDL-C) and apo(B) with Lp(a)-targeted siRNA
- LDL-C reduced by more than
- 20%
- Apo(B) decreased by approximately
- 15%
Safety
- Most drugs: favourable safety, no significant differences vs placebo
- Zerlasiran raised concerns re injection-site reactions and other adverse events vs placebo
Original publication
Comprehensive evaluation of siRNA therapeutics on Lp(a): A network meta‐analysis. Diabetes Obes Metab. Published 21 March 2025. doi:10.
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