Future Directions to Establish Lipoprotein(a) as a Treatment for Atherosclerotic Cardiovascular Disease

Abstract

In both epidemiologic and genetic studies, increased levels of Lp(a) have been associated with increased risk for cardiovascular diseases as well as aortic stenosis. However, until recently, it has been difficult to lower levels of Lp(a). Diet and lifestyle have little effect on plasma levels of Lp(a) which are mainly genetically determined. Emerging therapeutic agents which have recently become available, or which are undergoing clinical trials, can significantly lower Lp(a) levels. Studies with these agents will hopefully be able to provide more direct information whether reductions in Lp(a) will reduce CVD events independently of reduction in LDL-cholesterol levels.

The New Molecular Entity Evolocumab, One Kind of PCSK9 Inhibitor, Reduce Plasma Small Size LDL-Cholesterol Levels by Using a New Standardized Method of Measuring LDL Size

“…Recently, it has been reported that evolocumab treatment decreases Lp(a) levels. In vivo and in vitro data in this analysis support the hypothesis that the additional upregulation of LDLR activity by PCSK9 mAb also increases the clearance of Lp(a) [37]. by the JAS, risk factors besides hyperlipidemia are also carefully considered, and emphasis is placed on understanding the multiple risks resulting from the accumulation of such risks.…”

Prognostic value of lipoprotein (a) level in patients with coronary artery disease: a meta-analysis

“…Both life-style improvement and available lipid-lowering drugs seem to poorly affect blood levels of lipoprotein (a) [32, 33]. Mild reduction achievable with PCKS9 inhibitors or niacin seems not to be related to reduce cardiovascular events [34].…”

Toward an international consensus—Integrating lipoprotein apheresis and new lipid-lowering drugs

“…Niacin, PCSK9 inhibitors, the CETP inhibitor anacetrapib (investigational), and mipomersen (not approved in Europe) have the potential to lower Lp(a) by approximately 25% to 30%, but the CVD benefit is unknown. 18,75 The effect of PCSK9 inhibitors in Lp(a) levels is dependent on baseline Lp(a) levels, whereby high baseline Lp(a) (.125 nmol/L) is associated with diminished percentage reductions and greater absolute reductions compared with lower baseline levels (#125 nmol/L). 76 Certainly, for these drugs, reduction of Lp(a) levels is generally insufficient.…”