12 Recent Approaches to Lowering Lp(a): What the Studies Show Approaches that result in lowering of both Lp(a) and LDL Lipoprotein Apheresis (LA): Moriarty and colleagues reported that lipoprotein apheresis (LA) therapy can effectively reduce both LDL and Lp(a), with a significant reduction in future CVD events (94% reduction in major adverse cardiovascular events over a mean treatment period of 48 months).27 In the Pro(a)LiFe-Study (Lipoprotein Apheresis for Lipoprotein(a)- Associated Cardiovascular Disease: Prospective 5 Years of Follow-Up and Apolipoprotein(a) Characterization)28, it was shown that LA has a lasting effect on prevention of cardiovascular events in patients with Lp(a)- hyperlipidemia. Mean Lp(a) concentration was reduced in a single LA treatment by 68.1% on average and a significant decline of the mean annual cardiovascular event rate was observed from 0.58±0.53 2 years before regular LA to 0.11±0.15 thereafter. PCSK9 inhibitors reduce LDL-C by 43% to 64% and lower Lp(a) by 20% to 30%. Analysis of the ODYSSEY OUTCOMES and FOURIER outcomes trials showed enhanced benefit from PCSK9 inhibitor therapy in patients with elevated Lp(a) despite more modest (16-22%) Lp(a) percent lowering in this group.12 Inclisiran, a small interfering RNA molecule that targets PCSK9 messenger RNA, has been evaluated in people with high risk for CVD and elevated LDL-C. Compared with placebo, inclisiran reduced Lp(a) by 21.9% in the ORION-10 trial evaluating inclisiran in patients with ASCVD and by 18.6% in the ORION-11 trial that enrolled subjects with an ASCVD equivalent.29 Enlicitide, the first FDA-approved oral PCSK9 inhibitor, was approved in 2026 as an adjunct to diet and exercise to reduce LDL-C in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia. In CORALreef Lipids, enlicitide also produced a modest reduction in Lp(a) (approximately 28% versus placebo at 24 weeks). Cardiovascular outcomes data for enlicitide are not yet available.30
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