Related Experiment Video
Updated: Mar 24, 2026

Differential Effects of Lipid-lowering Drugs in Modulating Morphology of Cholesterol Particles
Published on: November 10, 2017
Efficacy and safety of lipoprotein(a)-targeted therapeutics: a systematic review and network meta-analysis
Jiaqiang Hu1, Jun Wang2, Haixia Zhang1
1Department of Pharmacy, Guang'an People's Hospital, Guang'an, Sichuan, China.
Background:
Lipoprotein(a)-targeted therapies are emerging approaches for lowering lipoprotein(a) [lp(a)].
Objective:
We conducted a systematic review and network meta-analysis to evaluate the efficacy and safety of lipoprotein(a)-targeted therapies in patients.
Methods:
We searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to May 6, 2025, for randomized controlled trials (RCTs) with intervention duration of at least 12 weeks. The primary outcomes were percentage and absolute changes in Lp(a). Secondary outcomes included changes in low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB), and safety outcomes including adverse events (AEs), serious adverse events (SAEs), and injection-site reactions. A frequentist framework network meta- analysis was performed.
Results:
Nine studies involving 1,432 participants were included. All six Lp(a)-targeted therapies significantly reduced Lp(a) levels. Compared with placebo, Olpasiran was the most effective therapy for both percentage [mean difference: -92.06, 95% (-109.80; -74.32), P-score: 0.94] and absolute reductions [-250.70 (-262.04; -239.36), P-score: 0.99], followed by Zerlasiran [-78.33 (-92.18; -64.48), P-score: 0.70], [-205.63 (-217.24; -194.03), P-score: 0.76]. In between-drug comparisons, Olpasiran was superior to Pelacarsen. Both Olpasiran and Zerlasiran were associated with improved LDL-C and apoB concentrations. Zerlasiran, Lepodisiran, and Pelacarsen were found to increase the risk of injection-site reactions.
Conclusions:
Lp(a)-targeted therapies achieved substantial reductions in Lp(a). Olpasiran was the most effective agent in lowering Lp(a) levels. These therapies also improved LDL-C and apoB. The majority of Lp(a)-targeted therapies demonstrate generally favorable safety profiles; However, injection-site reactions, particularly with Zerlasiran, warrant careful consideration.
Systematic Review Registration:
https://www.crd.york.ac.uk/PROSPERO/view/CRD420251069288, PROSPERO CRD420251069288.
Related Concept Videos
Pharmacogenomics: Identification of New Drug Targets
Atherosclerosis III: Management
Lipid-Lowering Drugs: Statins and Miscellaneous Agents
Modified-Release Drug Delivery Systems: Site-Targeted
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test

