Key result
Novel lipid-lowering therapies potently reduce atherogenic lipoproteins, cutting Lp(a) by up to ~92%.
Why the study?
Existing LDL cholesterol-lowering drugs have little impact on lipoprotein(a) or plasma triglycerides, two other risk factors for ASCVD, leaving many patients at high risk.
Do emerging lipid-lowering therapies targeting lipoprotein(a), apolipoprotein C-III, angiopoietin-like protein 3, and omega-3 fatty acids reduce residual atherosclerotic cardiovascular disease risk in patients with dyslipidemia?
Do emerging lipid-lowering therapies targeting lipoprotein(a), apolipoprotein C-III, angiopoietin-like protein 3, and omega-3 fatty acids reduce residual atherosclerotic cardiovascular disease risk in patients with dyslipidemia?
This review highlights that while antisense oligonucleotides and monoclonal antibodies against Lp(a), apoC-III, and ANGPTL3 achieve profound lipid reductions in early-phase trials and icosapent ethyl reduces cardiovascular events, definitive outcome trials and cost management are needed before novel biologics transform residual ASCVD risk management.
Answers are grounded in this paper and cite their sources.
May address residual ASCVD risk; leaves open confirmation of CV benefit in outcome trials.
The recent introduction of inhibitors of proprotein convertase subtilisin/kexin 9 to lower low-density lipoprotein (LDL) cholesterol on top of statins or as monotherapy is rapidly changing the landscape of treatment of atherosclerotic cardiovascular disease (ASCVD). However, existing lipid-lowering drugs have little impact on lipoprotein(a) (Lp(a)) or plasma triglycerides, two other risk factors for ASCVD. This review summarizes the evidence and the rationale to target Lp(a) and triglycerides and provides an overview of currently tested strategies to lower Lp(a), apolipoprotein C-III and angiopoietin-like protein 3. In addition, it summarizes new findings on the use of omega-3 fatty acids (OM3FA) to fight ASCVD. With the exception of OM3FA supplementation, the promise of the experimental drugs discussed here depends on the long-term safety and efficacy of monoclonal antibodies and/or antisense oligonucleotides Clinical outcome trials will ultimately prove whether these new therapeutic modalities will reduce ASCVD risk.
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Zwol et al. (2019) conducted a review in Atherosclerotic cardiovascular disease (ASCVD) and dyslipidemia (elevated lipoprotein(a) and hypertriglyceridemia). Emerging lipid-lowering therapies targeting Lp(a), apoC-III, ANGPTL3 (monoclonal antibodies and antisense oligonucleotides), and omega-3 fatty acids vs. Standard lipid-lowering therapy (statins) or placebo was evaluated. Antisense oligonucleotides and monoclonal antibodies targeting apo(a), apoC-III, and ANGPTL3 potently reduce Lp(a) up to 92% and triglycerides up to 71%, while icosapent ethyl reduces CV mortality by 25%.
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