A Short Review of New Drugs for Heart Failure: Omecamtiv Mecarbil and Vericiguat
Omecamtiv Mecarbil and Vericiguat
Abstract
Heart failure is associated with increased morbidity and mortality. Although developments of therapeutic agents have shown benefit and have improved the patients’ condition, there is only a slight decreased of mortality rate throughout the years. This condition becomes a reason to develop efficient drugs which can further improve the condition and reducing the mortality significantly. New therapeutic agents have been proposed and studied. Among them is cardiac myosin activator, such as omecamtiv mecarbil. This drug will increase the binding of myosin head to the actin and therefore form a stronger contraction. Omecamtiv mecarbil is beneficial due to its mechanism which not related to higher oxygen consumption and less adverse events. Another promising drug is vericiguat, a soluble guanylate cyclase (sGC) stimulator. This drug enhances the binding of nitric oxide to sGC and therefore increasing cyclic guanosine monophosphate (cGMP) production. cGMP important in regulating physiological processed in the cardiovascular system. In this review, we will discuss about the current evidence about these novel agents.
Keywords: heart failure, novel agent, omecamtiv mecarbil, vericiguat, management
Keywords:
heart failure, novel agent, omecamtiv mecarbil, vericiguat, managementDOI
https://doi.org/10.22270/jddt.v12i2-S.5432References
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6. Tariq S, Aronow WS. Use of Inotropic Agents in Treatment of Systolic Heart Failure. Int J Mol Sci. 2015; 16(12):29060-8. https://doi.org/10.3390/ijms161226147
7. Patel PH, Nguyen M, Rodriguez R, Surani S, Udeani G. Omecamtiv Mecarbil: A Novel Mechanistic and Therapeutic Approach to Chronic Heart Failure Management. Cureus. 2021; 13(1):e12419. https://doi.org/10.7759/cureus.12419
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9. Liu Y, White HD, Belknap B, Winkelmann DA, Forgacs E. Omecamtiv Mecarbil modulates the kinetic and motile properties of porcine β-cardiac myosin. Biochemistry. 2015; 54(10):1963-75. https://doi.org/10.1021/bi5015166
10. Spudich JA. Hypertrophic and dilated cardiomyopathy: four decades of basic research on muscle lead to potential therapeutic approaches to these devastating genetic diseases. Biophys J. 2014; 106(6):1236-49. https://doi.org/10.1016/j.bpj.2014.02.011
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16. Montfort WR, Wales JA, Weichsel A. Structure and Activation of Soluble Guanylyl Cyclase, the Nitric Oxide Sensor. Antioxid Redox Signal. 2017; 26(3):107-121. https://doi.org/10.1089/ars.2016.6693
17. Kuhn M. Molecular Physiology of Membrane Guanylyl Cyclase Receptors. Physiol Rev. 2016; 96(2):751-804. https://doi.org/10.1152/physrev.00022.2015
18. Lee DI, Zhu G, Sasaki T, Cho GS, Hamdani N, Holewinski R, et al. Phosphodiesterase 9A controls nitric-oxide-independent cGMP and hypertrophic heart disease. Nature. 2015; 519(7544):472-6. https://doi.org/10.1038/nature14332
19. Kokkonen K, Kass DA. Nanodomain Regulation of Cardiac Cyclic Nucleotide Signaling by Phosphodiesterases. Annu Rev Pharmacol Toxicol. 2017; 57:455-479. https://doi.org/10.1146/annurev-pharmtox-010716-104756
20. Marti CN, Gheorghiade M, Kalogeropoulos AP, Georgiopoulou VV, Quyyumi AA, Butler J. Endothelial dysfunction, arterial stiffness, and heart failure. J Am Coll Cardiol. 2012; 60(16):1455-69. https://doi.org/10.1016/j.jacc.2011.11.082
21. Burnett JC Jr. Vericiguat - Another Victory for Targeting Cyclic GMP in Heart Failure. N Engl J Med. May; 382(20):1952-1953. https://doi.org/10.1056/NEJMe2006855
22. Gheorghiade M, Marti CN, Sabbah HN, Roessig L, Greene SJ, Böhm M, et al. Soluble guanylate cyclase: a potential therapeutic target for heart failure. Heart Fail Rev. 2013; 18(2):123-34. https://doi.org/10.1007/s10741-012-9323-1
23. van Heerebeek L, Hamdani N, Falcão-Pires I, Leite-Moreira AF, Begieneman MP, Bronzwaer JG, van der Velden J, Stienen GJ, Laarman GJ, Somsen A, Verheugt FW, Niessen HW, Paulus WJ. Low myocardial protein kinase G activity in heart failure with preserved ejection fraction. Circulation. 2012; 126(7):830-9. https://doi.org/10.1161/CIRCULATIONAHA.111.076075
24. Kim GE, Kass DA. Cardiac Phosphodiesterases and Their Modulation for Treating Heart Disease. Handb Exp Pharmacol. 2017; 243:249-269. https://doi.org/10.1007/164_2016_82
25. Mattia A. Vericiguat in heart failure- who benefits the most?. Cardiovasc Med. 2021; 24:w10049. https://doi.org/10.4414/CVM.2021.w10049
26. Redfield MM, Chen HH, Borlaug BA, Semigran MJ, Lee KL, Lewis G, et al. Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial. JAMA. 2013; 309(12):1268-77. https://doi.org/10.1001/jama.2013.2024
27. Stasch JP, Pacher P, Evgenov OV. Soluble guanylate cyclase as an emerging therapeutic target in cardiopulmonary disease. Circulation. 2011; 123:2263-73. https://doi.org/10.1161/CIRCULATIONAHA.110.981738
28. Evgenov OV, Pacher P, Schmidt PM, Haskó G, Schmidt HH, Stasch JP. NO-independent stimulators and activators of soluble guanylate cyclase: discovery and therapeutic potential. Nat Rev Drug Discov. 2006; 5(9):755-68. https://doi.org/10.1038/nrd2038
29. Gheorghiade M, Greene SJ, Butler J, Filippatos G, Lam CS, Maggioni AP, et al. Effect of Vericiguat, a Soluble Guanylate Cyclase Stimulator, on Natriuretic Peptide Levels in Patients With Worsening Chronic Heart Failure and Reduced Ejection Fraction: The SOCRATES-REDUCED Randomized Trial. JAMA. 2015; 314(21):2251-62. https://doi.org/10.1001/jama.2015.15734
30. Armstrong PW, Pieske B, Anstrom KJ, Ezekowitz J, Hernandez AF, Butler Jet al. Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2020; 382(20):1883-1893. https://doi.org/10.1056/NEJMoa1915928
2. Berliner D, Bauersachs J. New drugs: big changes in conservative heart failure therapy?. Eur J Cardiothorac Surg. 2019; 55(Suppl 1):i3-i10. https://doi.org/10.1093/ejcts/ezy421
3. Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, et al. Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation. 2017; 135(10):e146-e603. https://doi.org/10.1161/CIR.0000000000000485
4. Straw S, McGinlay M, Witte KK. Four pillars of heart failure: contemporary pharmacological therapy for heart failure with reduced ejection fraction. Open Heart. 2021; 8(1):e001585. https://doi.org/10.1136/openhrt-2021-001585
5. Liu LC, Dorhout B, van der Meer P, Teerlink JR, Voors AA. Omecamtiv mecarbil: a new cardiac myosin activator for the treatment of heart failure. Expert Opin Investig Drugs. 2016; 25(1):117-27. https://doi.org/10.1517/13543784.2016.1123248
6. Tariq S, Aronow WS. Use of Inotropic Agents in Treatment of Systolic Heart Failure. Int J Mol Sci. 2015; 16(12):29060-8. https://doi.org/10.3390/ijms161226147
7. Patel PH, Nguyen M, Rodriguez R, Surani S, Udeani G. Omecamtiv Mecarbil: A Novel Mechanistic and Therapeutic Approach to Chronic Heart Failure Management. Cureus. 2021; 13(1):e12419. https://doi.org/10.7759/cureus.12419
8. Malik FI, Hartman JJ, Elias KA, Morgan BP, Rodriguez H, Brejc K, et al. Cardiac myosin activation: a potential therapeutic approach for systolic heart failure. Science. 2011; 331(6023):1439-43. https://doi.org/10.1126/science.1200113
9. Liu Y, White HD, Belknap B, Winkelmann DA, Forgacs E. Omecamtiv Mecarbil modulates the kinetic and motile properties of porcine β-cardiac myosin. Biochemistry. 2015; 54(10):1963-75. https://doi.org/10.1021/bi5015166
10. Spudich JA. Hypertrophic and dilated cardiomyopathy: four decades of basic research on muscle lead to potential therapeutic approaches to these devastating genetic diseases. Biophys J. 2014; 106(6):1236-49. https://doi.org/10.1016/j.bpj.2014.02.011
11. Teerlink JR, Clarke CP, Saikali KG, Lee JH, Chen MM, Escandon RD, et al. Dose-dependent augmentation of cardiac systolic function with the selective cardiac myosin activator, omecamtiv mecarbil: a first-in-man study. Lancet. 2011; 378(9792):667-75. https://doi.org/10.1016/S0140-6736(11)61219-1
12. Greenberg BH, Chou W, Saikali KG, Escandón R, Lee JH, Chen MM, et al. Safety and tolerability of omecamtiv mecarbil during exercise in patients with ischemic cardiomyopathy and angina. JACC Heart Fail. 2015; 3(1):22-29. https://doi.org/10.1016/j.jchf.2014.07.009
13. Teerlink JR, Felker GM, McMurray JJV, Ponikowski P, Metra M, Filippatos GS, et al. Acute Treatment With Omecamtiv Mecarbil to Increase Contractility in Acute Heart Failure: The ATOMIC-AHF Study. J Am Coll Cardiol. 2016; 67(12):1444-1455. https://doi.org/10.1016/j.jacc.2016.01.031
14. Teerlink JR, Felker GM, McMurray JJ, Solomon SD, Adams KF, Cleland JG, et al. Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure (COSMIC-HF): a phase 2, pharmacokinetic, randomised, placebo-controlled trial. Lancet. 2016; 388(10062):2895-2903. https://doi.org/10.1016/S0140-6736(16)32049-9
15. Teerlink JR, Diaz R, Felker GM, McMurray JJV, Metra M, Solomon SD, et al. Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure. N Engl J Med. 2021; 384(2):105-116. https://doi.org/10.1056/NEJMoa2025797
16. Montfort WR, Wales JA, Weichsel A. Structure and Activation of Soluble Guanylyl Cyclase, the Nitric Oxide Sensor. Antioxid Redox Signal. 2017; 26(3):107-121. https://doi.org/10.1089/ars.2016.6693
17. Kuhn M. Molecular Physiology of Membrane Guanylyl Cyclase Receptors. Physiol Rev. 2016; 96(2):751-804. https://doi.org/10.1152/physrev.00022.2015
18. Lee DI, Zhu G, Sasaki T, Cho GS, Hamdani N, Holewinski R, et al. Phosphodiesterase 9A controls nitric-oxide-independent cGMP and hypertrophic heart disease. Nature. 2015; 519(7544):472-6. https://doi.org/10.1038/nature14332
19. Kokkonen K, Kass DA. Nanodomain Regulation of Cardiac Cyclic Nucleotide Signaling by Phosphodiesterases. Annu Rev Pharmacol Toxicol. 2017; 57:455-479. https://doi.org/10.1146/annurev-pharmtox-010716-104756
20. Marti CN, Gheorghiade M, Kalogeropoulos AP, Georgiopoulou VV, Quyyumi AA, Butler J. Endothelial dysfunction, arterial stiffness, and heart failure. J Am Coll Cardiol. 2012; 60(16):1455-69. https://doi.org/10.1016/j.jacc.2011.11.082
21. Burnett JC Jr. Vericiguat - Another Victory for Targeting Cyclic GMP in Heart Failure. N Engl J Med. May; 382(20):1952-1953. https://doi.org/10.1056/NEJMe2006855
22. Gheorghiade M, Marti CN, Sabbah HN, Roessig L, Greene SJ, Böhm M, et al. Soluble guanylate cyclase: a potential therapeutic target for heart failure. Heart Fail Rev. 2013; 18(2):123-34. https://doi.org/10.1007/s10741-012-9323-1
23. van Heerebeek L, Hamdani N, Falcão-Pires I, Leite-Moreira AF, Begieneman MP, Bronzwaer JG, van der Velden J, Stienen GJ, Laarman GJ, Somsen A, Verheugt FW, Niessen HW, Paulus WJ. Low myocardial protein kinase G activity in heart failure with preserved ejection fraction. Circulation. 2012; 126(7):830-9. https://doi.org/10.1161/CIRCULATIONAHA.111.076075
24. Kim GE, Kass DA. Cardiac Phosphodiesterases and Their Modulation for Treating Heart Disease. Handb Exp Pharmacol. 2017; 243:249-269. https://doi.org/10.1007/164_2016_82
25. Mattia A. Vericiguat in heart failure- who benefits the most?. Cardiovasc Med. 2021; 24:w10049. https://doi.org/10.4414/CVM.2021.w10049
26. Redfield MM, Chen HH, Borlaug BA, Semigran MJ, Lee KL, Lewis G, et al. Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial. JAMA. 2013; 309(12):1268-77. https://doi.org/10.1001/jama.2013.2024
27. Stasch JP, Pacher P, Evgenov OV. Soluble guanylate cyclase as an emerging therapeutic target in cardiopulmonary disease. Circulation. 2011; 123:2263-73. https://doi.org/10.1161/CIRCULATIONAHA.110.981738
28. Evgenov OV, Pacher P, Schmidt PM, Haskó G, Schmidt HH, Stasch JP. NO-independent stimulators and activators of soluble guanylate cyclase: discovery and therapeutic potential. Nat Rev Drug Discov. 2006; 5(9):755-68. https://doi.org/10.1038/nrd2038
29. Gheorghiade M, Greene SJ, Butler J, Filippatos G, Lam CS, Maggioni AP, et al. Effect of Vericiguat, a Soluble Guanylate Cyclase Stimulator, on Natriuretic Peptide Levels in Patients With Worsening Chronic Heart Failure and Reduced Ejection Fraction: The SOCRATES-REDUCED Randomized Trial. JAMA. 2015; 314(21):2251-62. https://doi.org/10.1001/jama.2015.15734
30. Armstrong PW, Pieske B, Anstrom KJ, Ezekowitz J, Hernandez AF, Butler Jet al. Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2020; 382(20):1883-1893. https://doi.org/10.1056/NEJMoa1915928
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2022-04-15
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Laksono S, Pratama AP, Halomoan R, Andra CA. A Short Review of New Drugs for Heart Failure: Omecamtiv Mecarbil and Vericiguat: Omecamtiv Mecarbil and Vericiguat. J. Drug Delivery Ther. [Internet]. 2022 Apr. 15 [cited 2026 Jan. 21];12(2-S):206-9. Available from: https://jddtonline.info/index.php/jddt/article/view/5432
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How to Cite
1.
Laksono S, Pratama AP, Halomoan R, Andra CA. A Short Review of New Drugs for Heart Failure: Omecamtiv Mecarbil and Vericiguat: Omecamtiv Mecarbil and Vericiguat. J. Drug Delivery Ther. [Internet]. 2022 Apr. 15 [cited 2026 Jan. 21];12(2-S):206-9. Available from: https://jddtonline.info/index.php/jddt/article/view/5432
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