Effect of lipid-lowering therapies on lipoprotein(a) levels: a comprehensive meta-analysis of randomized controlled trials
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…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 145,314 participants or records.
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