Effect of lipid-lowering therapies on lipoprotein(a) levels: a comprehensive meta-analysis of randomized controlled trials

source extracted confidence: high 2026-04-09
#humans #atherosclerosis #biomarkers #dyslipidemias #hypolipidemic-agents

Effect of lipid-lowering therapies on lipoprotein(a) levels: a comprehensive meta-analysis of randomized controlled trials

Xie et al., 2025 | Atherosclerosis | Meta Analysis

Citation

Xie Sining, Galimberti Federica, ... Casula Manuela. Effect of lipid-lowering therapies on lipoprotein(a) levels: a comprehensive meta-analysis of randomized controlled trials. Atherosclerosis. 2025-Sep;408:120420. doi:10.1016/j.atherosclerosis.2025.120420

Abstract

BACKGROUND AND AIMS: Lipoprotein (a) [Lp(a)] is an independent and causal risk factor for atherosclerotic cardiovascular disease. In this study we aimed at assessing the effect of currently available lipid-lowering therapies (LLTs) on Lp(a) plasma levels. METHODS: A meta-analysis was performed according to the PRISMA guidelines. Databases were searched up to May 2025. Inclusion criteria were: (1) randomized controlled trials (RCTs) in adults (≥18 years), phase II, III or IV; (2) English language; (3) comparing the effect of lipid-lowering drugs vs placebo (addition of the same drug to both intervention and control group was acceptable); (4) reporting the effects on Lp(a) levels; (5) intervention duration of more than 3 weeks. The between-group (treatment-placebo) Lp(a) absolute mean differences and 95% confidence intervals were calculated for each drug class separately. RESULTS: A total of 145,314 subjects from 147 RCTs were included. Statins, bempedoic acid, ezetimibe, omega-3 fatty acids, and fibrates did not affect Lp(a) concentration. Lp(a) levels were significantly reduced by PCSK9 monoclonal antibodies (PCSK9mAbs, -6.37 mg/dL [-7.26 to -5.47], a 29% reduction from baseline), inclisiran (-4.76 mg/dL [-5.83 to -3.69], a 22% reduction from baseline), CETP inhibitors (CETPi, -6.77 mg/dL [-8.67 to -4.88], a 46% reduction from baseline), and niacin (-7.06 mg/dL [-9.27 to -4.85], a 37% reduction from baseline). In the subgroup analysis by baseline Lp(a) levels, a larger absolute reduction of Lp(a) levels was observed with increasing baseline levels of Lp(a) for PCSK9mAbs, inclisiran, and CETPi. CONCLUSIONS: Among available LLTs, PCSK9mAbs, inclisiran, CETPi, and niacin significantly decreased Lp(a) levels. Further research is necessary to understand whether this effect would translate into a clinically relevant cardiovascular benefit.

Key Findings

A total of 145,314 subjects from 147 RCTs were included. Statins, bempedoic acid, ezetimibe, omega-3 fatty acids, and fibrates did not affect Lp(a) concentration. Lp(a) levels were significantly reduced by PCSK9 monoclonal antibodies (PCSK9mAbs, -6.37 mg/dL [-7.26 to -5.47], a 29% reduction from baseline), inclisiran (-4.76 mg/dL [-5.83 to -3.69], a 22% reduction from baseline), CETP inhibitors (CETPi, -6.77 mg/dL [-8.67 to -4.88], a 46% reduction from baseline), and niacin (-7.06 mg/dL [-9.27 t

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size 145314
Age Range See abstract
Condition See abstract

MeSH Terms

  • Humans
  • Atherosclerosis
  • Biomarkers
  • Dyslipidemias
  • Hypolipidemic Agents
  • Lipoprotein(a)
  • Randomized Controlled Trials as Topic
  • Treatment Outcome

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't
  • Vertical: niacin

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09