Lipoprotein(a) the Insurgent: A New Insight into the Structure, Function, Metabolism, Pathogenicity, and Medications Affecting Lipoprotein(a) Molecule

Table 3

Summary of approved and investigational therapeutic drugs to lower LDL & Lp(a).

Mechanism	Approved and investigational therapeutic drugs to lower LDL & Lp(a)
	Agent	Status	Is it specific for Lp(a)?	LDL∆%	Lp(a)∆%	Comment	Ref
Reduce production of new LDL/Lp(a)	Statins	Approved	No	19–49↓	0 –20↑	The effect of statins on Lp(a) is controversial. However, statins lower LDL-C and risk of CVD events	[17, 203, 205]
	Niacin	Approved	No	Up to 45↓	30–40↓	Does not reduce CV risk. However, EAS recommends the use of niacin to achieve an Lp(a) concentration less than 500 mg/L	[206, 207]
	IONIS-APO(a)-LRx (AKCEA-APO(a)-LRx)	Investigational	Yes	–	39–92↓	Most promising agent, which is an ASO that specifically targets apo(a) mRNA	[17, 208, 209]
	AMG 890	Investigational	Yes	–	90%↓	siRNA directed to apo(a) mRNA to block mRNA translation. This lowering was shown in primates	[210]
	Mipomersen	Approved	No	21–40↓	20–33↓	ApoB ASO, which decreases LDL synthesis. For patients with HoFH	[17, 183, 211, 212]
	Lomitapide	Approved	No	19–51↓	15–17↓	Decreases VLDL production via MTTP inhibition. Approved for patients with HoFH	[212, 213]
	CETP inhibitors	Stopped	No	14–26↓	36–39↓	Increases levels of HDL-C and reduces levels of LDL-C	[205, 214–216]
	Aspirin	Approved	No	–	10–80↓	Aspirin reduces apo(a) by suppression of apo(a) gene transcription	[207, 217]
Increase LDLR expression for LDL/ Lp(a) uptake	Evolocumab	Approved	No	39–75↓	30↓	PCSK9 inhibition leads to the recycling of LDLR back to hepatocyte surface for LDL/Lp(a) molecule uptake	[218–221]
	Alirocumab	Approved	No	29–73 ↓	30↓	Same as above agent	[218, 219, 222]
	Inclisiran	Investigational	No	Up to 60↓	25.6↓	siRNA directed to PCSK9 mRNA, leading to significant and constant blocking of the production of PCSK9 protein	[223, 224]
Physical elimination of Lp(a) molecules	Apheresis	Approved	No	80↓	68–75↓	Remove all apo-B100-containing particles in a single session. Most effective—expensive with limited access to facilities	[183, 225]
	Lp(a)-apheresis	Information not available	Yes	–	70–80↓	Remove Lp(a) only in a single session by immunoadsorption	[226, 227]