Current Evidence and Future Perspectives on Pharmacological Treatment of Calcific Aortic Valve Stenosis
Abstract
:1. Introduction
2. Methods
3. Pathophysiology of CAVS
4. Purpose
5. Lipid-Lowering Interventions
5.1. Statins
5.1.1. Current Evidence
5.1.2. Future Perspectives
5.2. Lp(a)-Lowering Therapies
5.2.1. Current Evidence
5.2.2. Future Perspectives
5.3. PCSK9 Inhibitors
5.3.1. Current Evidence
5.3.2. Future Perspectives
6. RAAS Blockade
6.1. ACE Inhibitors/ARBs
6.1.1. Current Evidence
6.1.2. Future Perspectives
6.2. Mineralocorticoid Receptor Antagonists
6.2.1. Current Evidence
6.2.2. Future Perspectives
7. Modulators of Nitric Oxide Pathway
7.1. Current Evidence
7.2. Future Perspectives
8. Anti-Calcific Agents
8.1. Inhibitors of Bone Resorption
8.1.1. Current Evidence
8.1.2. Future Perspectives
8.2. Vitamin K
8.2.1. Current Evidence
8.2.2. Future Perspectives
9. Emerging Targets
9.1. Nox2
9.2. ENPP1 and P2Y2
9.3. DPP-4
9.4. Cadherin-11
9.5. PPARγ
10. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Trial Name | NCT | Treatment | Phase | Population | Enrolment (No. of Patients) | Primary Outcome |
---|---|---|---|---|---|---|
EAVaLL | NCT02109614 | Extended-release niacin vs. placebo | I | Aortic sclerosis or mild CAVS | 238 | Calcium score progression measured by cardiac CT at 2 years |
NCT03051360 | PCSK9 inhibitor vs. placebo | II | Mild to moderate CAVS | 140 | Calcium score progression measured by cardiac CT and by NaF PET at 2 years | |
NCT02481258 | Ataciguat vs. placebo | II | Moderate CAVS | 35 | Changes in AV calcium levels at 6 months | |
SALTIRE II | NCT02132026 | Alendronate/denosumab vs. placebo | II | Peak aortic jet velocity >2.5 m/s and grade 2–4 calcification of the AV on echocardiography | 150 | Change in AV calcium score at 6 months and 2 years |
AVADEC | NCT03243890 | Menaquinone-7 vs. placebo | - | AV calcification score above 300, but without clinical CAVS | 389 | Change in AV calcification at 2 years |
BASIK2 | NCT02917525 | Vitamin K2 vs. placebo | II | Bicuspid AV and mild to moderate CAVS on prior echocardiography | 44 | Change in AV calcium metabolism measured by NaF PET at 6 months |
Target | Treatment | Effects | Model | Ref. |
---|---|---|---|---|
Nox2 | Celastrol | Nox2 inhibition mitigates the severity of aortic valve fibrosis, calcification, and stenosis | rabbit | [190] |
ENPP1 | ARL67156 | The inhibition of ENPP1 prevents the development of CAVS | rat | [191] |
P2Y2 | 2-thioUTP | P2Y2 agonist promotes the regression of CAVS | mouse | [192] |
DPP-4 | Sitagliptin | DPP-4 inhibition prevents CAVS development | rabbit | [193] |
Cadherin-11 | SYN0012 | Cad-11-blocking antibody prevents Notch1-mediated CAVS | mouse | [194] |
PPARγ | Pioglitazone | PPARγ agonist attenuates the progression of aortic valve calcification | rabbit | [195] |
PPARγ agonist attenuates lipid deposition, calcification, and apoptosis in aortic valves | mouse | [196] |
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Donato, M.; Ferri, N.; Lupo, M.G.; Faggin, E.; Rattazzi, M. Current Evidence and Future Perspectives on Pharmacological Treatment of Calcific Aortic Valve Stenosis. Int. J. Mol. Sci. 2020, 21, 8263. https://doi.org/10.3390/ijms21218263
Donato M, Ferri N, Lupo MG, Faggin E, Rattazzi M. Current Evidence and Future Perspectives on Pharmacological Treatment of Calcific Aortic Valve Stenosis. International Journal of Molecular Sciences. 2020; 21(21):8263. https://doi.org/10.3390/ijms21218263
Chicago/Turabian StyleDonato, Maristella, Nicola Ferri, Maria Giovanna Lupo, Elisabetta Faggin, and Marcello Rattazzi. 2020. "Current Evidence and Future Perspectives on Pharmacological Treatment of Calcific Aortic Valve Stenosis" International Journal of Molecular Sciences 21, no. 21: 8263. https://doi.org/10.3390/ijms21218263
APA StyleDonato, M., Ferri, N., Lupo, M. G., Faggin, E., & Rattazzi, M. (2020). Current Evidence and Future Perspectives on Pharmacological Treatment of Calcific Aortic Valve Stenosis. International Journal of Molecular Sciences, 21(21), 8263. https://doi.org/10.3390/ijms21218263