Classical and Novel Lipid-Lowering Therapies for Diabetic Patients with Established Coronary Artery Disease or High Risk of Coronary Artery Disease—A Narrative Clinical Review
Abstract
:1. Introduction
2. Guidelines for Dyslipidemia Therapy in Patients with Type 2 Diabetes
- Very high CV risk: Individuals with T2DM with established ASCVD or severe damage of target organs, or an estimated 10-year CVD risk above 20% using SCORE2-Diabetes
- High CV risk: Individuals with T2DM without established ASCVD or severe damage of target organs, but an estimated 10-year CVD risk of 10–20% using SCORE2-Diabetes
- Moderate CV risk: Individuals with T2DM without established ASCVD or severe damage of target organs, but an estimated 10-year CVD risk of 5–10% using SCORE2-Diabetes
- Low CV risk: Individuals with T2DM without established ASCVD or severe damage of target organs, but an estimated 10-year CVD risk below 5% using SCORE2-Diabetes
3. Classical Lipid-Lowering Medications
3.1. Statins
3.1.1. Statins and Cardiovascular Outcomes
3.1.2. Aggressive vs. Conventional Statin Therapy
3.1.3. Adverse Effects of Statins
3.2. Ezetimibe
3.2.1. Effects of Ezetimibe on Lipid Profile
3.2.2. Effects of Ezetimibe on Cardiovascular Outcomes
3.2.3. Ezetimibe Side Effects
3.3. PCSK9 Inhibitors
3.3.1. Effects of PCSK9 Inhibitors on Lipid Profile
3.3.2. Effects of PCSK9 Inhibitors on Cardiovascular Outcomes
3.3.3. Side Effects of PCSK9 Inhibitors
3.4. Fibrates
3.4.1. Effects of Fibrates on Lipid Profile
3.4.2. Effects of Fibrates on Cardiovascular Outcomes
3.4.3. Side Effects of Fibrates
3.5. Omega-3 Fatty Acids
3.5.1. Effects of Omega-3 Fatty Acids on Lipid Profile
3.5.2. Effects of Omega-3 Fatty Acids on Cardiovascular Outcomes
3.5.3. Omega-3 Fatty Acid Side Effects
4. Novel Lipid-Lowering Medications
4.1. Bempedoic Acid
4.1.1. Effects of Bempedoic Acid on Lipid Profile
4.1.2. Effects of Bempedoic Acid on Cardiovascular Outcomes
4.1.3. Side Effects of Bempedoic Acid
4.2. Inclisiran
4.2.1. Effects of Inclisiran on Lipid Profile
4.2.2. Effects of Inclisiran on Cardiovascular Outcomes
4.2.3. Side Effects of Inclisiran
4.3. Ethyl Icosapentaenoic Acid
5. Antilipidemic Effects of Anti-Diabetic and Anti-Hypertensive Medications
6. Future Prospectives
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Drugs | Mechanisms | Lipid Changes and Clinical Outcomes | Side Effects |
---|---|---|---|
Statins | Inhibition of HMG-CoA reductase, ↓↓↓ endogenous production of LDL-C, ↑ clearance of atherogenic lipoproteins | ↓↓↓ LDL-C, ↓↓ sdLDL, ↔ HDL-C, ↓ TG ↓↓ CV morbidity and mortality in diabetic patients, especially those with already-existing CAD Dose-dependent manner of LDL-C reduction Greater clinical effect by high-intensity statins | Fatigue, myalgias, nervous system symptoms Less frequent: significant elevations in CPK/rhabdomyolysis |
Ezetimibe | Suppression of NPCL1 protein | ↓↓ LDL-C, ↓ TG, ↓ sdLDL, ↑ HDL-C ↓↓ MACE ↔ mortality after ACS | - |
PCSK9 inhibitors | Binding of PCSK9 facilitates LDL receptor degradation in liver | ↓↓↓ LDL-C, ↑ HDL-C, ↓ TG, ↓ non-HDL-C, ↓ Lp(a) ↓↓ CV morbidity | Limited adverse effects |
Fibrates | Activation of PPAR-α | ↓↓ TG, ↓ total cholesterol, ↑ HDL-C ↓↓ or ↔ CV events | Myopathy, rhabdomyolysis ↑ CPK, renal impairment, VTE (pemafribate) |
Omega-3 | ↓↓ hepatic lipogenesis, ↑ β-oxidation of fatty acids, ↓ enzymes mediating TG synthesis, ↑ lipoprotein lipase | ↓↓ TGs ↓ or ↔ CV morbidity and mortality | Atrial fibrillation |
Drug | Mechanisms | Lipid Profile Changes and Clinical Outcomes | Adverse Effects |
---|---|---|---|
Bempedoic acid Dose: 180 mg O.D. | Inhibition of ATP citrate lyase action, located upstream of the HMGCR | ↓↓ LDL-C ↓↓ risk of fatal or nonfatal MI ↓ or ↔ risk of coronary revascularization ↓↓ 10-year cardiovascular risk | Mild adverse effects: gout, hyperuricemia, cholelithiasis, ↑ aminotransferase, kidney impairment, ± headaches, myalgias |
Inclisiran Dose: 284 mg SC injection, repeat in 3 mo and then every 6 mo | ↓↓↓ expression of PCSK9 gene High specificity to hepatocytes | ↓↓↓ LDL-C ↑ HDL-C, ↓ Lp(a), ApoB ↔ risk of fatal or nonfatal MI ↓↓ risk of MACE | No serious adverse effects, similar to placebo group |
Ethyl eicosapentaenoic acid Dose: 2 g B.D. | ↓↓ hepatic lipogenesis ↑↑ β-oxidation of fatty acids ↓↓ TG synthesis ↑↑ expression of lipoprotein lipase | ↓↓ risk of composite endpoint: CV death, nonfatal MI, nonfatal stroke, coronary revascularization or unstable angina ↔ risk of major coronary event ↓↓ risk of nonfatal MI, CAD | Mild adverse effects: atrial fibrillation, peripheral edema, constipation |
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Velidakis, N.; Stachteas, P.; Gkougkoudi, E.; Papadopoulos, C.; Kadoglou, N.P.E. Classical and Novel Lipid-Lowering Therapies for Diabetic Patients with Established Coronary Artery Disease or High Risk of Coronary Artery Disease—A Narrative Clinical Review. Pharmaceuticals 2024, 17, 568. https://doi.org/10.3390/ph17050568
Velidakis N, Stachteas P, Gkougkoudi E, Papadopoulos C, Kadoglou NPE. Classical and Novel Lipid-Lowering Therapies for Diabetic Patients with Established Coronary Artery Disease or High Risk of Coronary Artery Disease—A Narrative Clinical Review. Pharmaceuticals. 2024; 17(5):568. https://doi.org/10.3390/ph17050568
Chicago/Turabian StyleVelidakis, Nikolaos, Panagiotis Stachteas, Evangelia Gkougkoudi, Christodoulos Papadopoulos, and Nikolaos P. E. Kadoglou. 2024. "Classical and Novel Lipid-Lowering Therapies for Diabetic Patients with Established Coronary Artery Disease or High Risk of Coronary Artery Disease—A Narrative Clinical Review" Pharmaceuticals 17, no. 5: 568. https://doi.org/10.3390/ph17050568