Can Lp(a) Lowering Against Background Statin Therapy Really Reduce Cardiovascular Risk?
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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.
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.
KeywordsLp(a) Statins PCSK9 inhibitors Familial hypercholesterolemia Mipomersen Lomitapide AKCEA-APO(a)-LRx
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Conflict of Interest
Dr. Reiner reports lecture honoraria from Akcea and Sanofi, outside the submitted work.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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