RNA therapeutics
Whether lowering Lp(a) on top of statins reduces cardiovascular risk remains unproven, a review of PCSK9 inhibitors and antisense drugs (Curr Atheroscler Rep 2019)
Original title: Can Lp(a) Lowering Against Background Statin Therapy Really Reduce Cardiovascular Risk?
This review by Reiner asks whether new drugs that lower Lp(a) can prevent atherosclerotic cardiovascular disease (ASCVD) and reduce ASCVD mortality when added to statin therapy. Genetic findings confirm elevated Lp(a), like elevated LDL cholesterol, is likely causally related to premature ASCVD, but Lp(a) is largely refractory to lifestyle interventions and statin effects on Lp(a) are inconsistent. Mipomersen and lomitapide lower Lp(a) alongside LDL cholesterol but carry unpleasant side effects, while the antisense oligonucleotide AKCEA-APO(a)Rx selectively lowers Lp(a). PCSK9 inhibitors alirocumab and evolocumab reduce both LDL cholesterol and Lp(a) and prevent ASCVD events on top of statin therapy, but it remains unclear whether their benefit stems from Lp(a) lowering or from LDL cholesterol reduction below levels achievable with statins alone. The author concludes ongoing trials should clarify whether Lp(a)-specific lowering adds cardiovascular benefit.
Original abstract
Purpose Of Review: The association between elevated plasma levels of lipoprotein (a) [Lp(a)] and atherosclerotic cardiovascular disease (ASCVD) has been discussed for many years. Recent genetic findings have confirmed that elevated Lp(a) similar to elevated LDL-cholesterol (LDL-C) might be causally related to premature ASCVD. Lp(a) is relatively refractory to lifestyle interventions. The results of studies with statins and their possible effect on Lp(a) are conflicting. Specific Lp(a) apheresis is used as a treatment against background statin therapy and can decrease Lp(a). The purpose of this review is to discuss whether new drugs which decrease Lp(a) can prevent ASCVD and decrease ASCVD mortality when applied in addition to statins.
Recent Findings: Some new LDL-C-lowering drugs such as mipomersen and lomitapide decrease elevated Lp(a) in addition to statins but they have some unpleasant adverse effects. Recently, an antisense oligonucleotide against apo(a), AKCEA-APO(a)Rx, has been shown to selectively decrease Lp(a). The most recent advance in LDL-C lowering are PCSK9 inhibitors. Alirocumab and evolocumab do not only significantly reduce LDL-C on top of maximally tolerated statin therapy and prevent ASCVD events, but also further decrease Lp(a). There is no data to indicate whether mipomersen, lomitapide, or IONIS-APO(a)-LRx decrease ASCVD events and mortality. Conclusive evidence is still lacking as to whether the treatment with PCSK9 inhibitors against background statin therapy actually additionally reduces ASCVD risk due to the lowering of Lp(a) or simply due to lowering LDL-C to levels much lower than high-intensity statin treatment as monotherapy. Ongoing trials will probably provide an answer to these questions.
PCSK9 inhibitionRNA therapeuticsstatins
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.