The class
CETP inhibitors cut lipoprotein(a) by 46 percent, the largest reduction among all lipid-lowering drug classes in a 147-trial meta-analysis (Atherosclerosis 2025)
Original title: Effect of lipid-lowering therapies on lipoprotein(a) levels: a comprehensive meta-analysis of randomized controlled trials
This meta-analysis assessed the effect of currently available lipid-lowering therapies on lipoprotein(a) [Lp(a)] plasma levels, a causal, independent risk factor for atherosclerotic cardiovascular disease. Following PRISMA guidelines, researchers included 147 randomized controlled trials covering 145,314 subjects comparing lipid-lowering drugs against placebo, with intervention durations over 3 weeks. Statins, bempedoic acid, ezetimibe, omega-3 fatty acids, and fibrates did not affect Lp(a) concentration, while Lp(a) was significantly reduced by PCSK9 monoclonal antibodies (-6.37 mg/dL, a 29% reduction from baseline), inclisiran (-4.76 mg/dL, 22%), niacin (-7.06 mg/dL, 37%), and CETP inhibitors (-6.77 mg/dL, a 46% reduction from baseline, the largest percentage reduction of any drug class studied). Larger absolute Lp(a) reductions were seen at higher baseline Lp(a) levels for PCSK9 monoclonal antibodies, inclisiran, and CETP inhibitors, though whether this effect translates into clinical cardiovascular benefit remains unknown.
Original 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.