Newer and Emerging LDL-C Lowering Agents and Implications for ASCVD Residual Risk
Abstract
:1. Introduction
2. Statins
3. Ezetimibe
4. Bempedoic Acid
5. Proprotein Convertase Subtilisin-Kexin Type 9 (PCSK9) Inhibition
6. Angiopoietin-Related Protein 3 (ANGPTL3)
7. Cholesteryl Ester Transfer Protein (CETP) Inhibitors
8. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Drug | Target | LDL-C Impact | Clinical Use or Status |
---|---|---|---|
Statins [7,8] | (HMG)-CoA reductase | ~50% | DM Severe hypercholesterolemia ASCVD PCE ≥ 7.5% |
Ezetimibe [7] | NPC1L1 | ~20% | Add-on to statin therapy for: ASCVD and LDL-C ≥ 70 mg/dL Severe hypercholesterolemia and LDL-C ≥ 100 mg/dL |
Bempedoic acid [9,10,11] | ATP-citrate lyase | ~20–25% | Add-on therapy (FDA 2/2020): ASCVD Heterozygous familial hypercholesterolemia |
Alirocumab and Evolocumab [7] | Plasma PCSK9 | ~60% | Add-on to statin and ezetimibe therapy (FDA 7/2015): ASCVD and LDL-C ≥ 70 mg/dL Severe hypercholesterolemia and LDL-C ≥ 100 mg/dL |
Inclisiran [12,13] | PCSK9 mRNA | ~50% | Add-on therapy (FDA 12/2021): ASCVD Heterozygous familial hypercholesterolemia |
MK-0616 [14,15,16] | Plasma PCSK9 | ~65% | Phase 2 upcoming |
AZD8233 [17] | PCSK9 mRNA | ~45–50% | Non-human primate data |
VERVE-101 [18] | PCSK9 | ~60% | Non-human primate data |
Evinacumab [19,20] | ANGPTL3 | ~50% | Add-on therapy (FDA 2/2021): Homozygous familial hypercholesterolemia |
ANGPTL3-LRX [21] | ANGPTL3 mRNA | ~50% | Development Terminated |
ARO-ANG3 [22,23,24,25] | ANGPTL3 mRNA | ~50% | Phase 2, actively recruiting |
Evacetrapib [26] | CETP | ~40% | Development Terminated |
Anacetrapib [27] | CETP | ~40% | Development Terminated |
Obicetrapib [28,29] | CETP | ~45% | Phase 3, actively recruiting |
Drug | Advantages | Disadvantages |
---|---|---|
Statins [7,8] | Excellent LDL-C lowering Strong evidence reducing ASCVD risk Six of the seven statins are generic | Low adherence |
Ezetimibe [7] | Well tolerated Moderate evidence in secondary prevention | Modest LDL-C lowering |
Bempedoic acid [9,10,11] | Well tolerated in those with statin associated side effects | Modest LDL-C lowering |
Alirocumab and Evolocumab [7] | Excellent LDL-C lowering Well tolerated Strong evidence reducing ASCVD risk | Cost Injection |
Inclisiran [12,13] | Excellent LDL-C lowering Durability (only 3 injections first year) | No ASCVD outcome data |
Evinacumab [19,20] | Excellent LDL-C lowering (Use in homozygous familial hypercholesterolemia) | Cost Injection |
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Rikhi, R.; Shapiro, M.D. Newer and Emerging LDL-C Lowering Agents and Implications for ASCVD Residual Risk. J. Clin. Med. 2022, 11, 4611. https://doi.org/10.3390/jcm11154611
Rikhi R, Shapiro MD. Newer and Emerging LDL-C Lowering Agents and Implications for ASCVD Residual Risk. Journal of Clinical Medicine. 2022; 11(15):4611. https://doi.org/10.3390/jcm11154611
Chicago/Turabian StyleRikhi, Rishi, and Michael D. Shapiro. 2022. "Newer and Emerging LDL-C Lowering Agents and Implications for ASCVD Residual Risk" Journal of Clinical Medicine 11, no. 15: 4611. https://doi.org/10.3390/jcm11154611