The Current Evolutions in the Pharmacotherapeutic Management of Heart Failure
Abstract
The heart failure remains as global pandemic, more than 23 million people are suffering from heart failure worldwide. The morbidity, mortality and economic burden are increasing rapidly day by day. In order to overcome this situation novel therapies to be developed to treat the heart failure. Many novel therapies accomplished all phases of clinical trials and ruling the pharmaceutical market such as sacubitril valsartan with a positive outcome on heart failure. Some new promising potent compounds such as vericiguat, omecamtiv mecarbil proved themselves by reducing HF complications. In addition, researchers are working very keenly in order to develop to new drug therapies for heart failure. In recent days, many new clinical instances have reported in development of drugs mainly to manage HF patients with mid-range and preserved left ventricular ejection fraction. This article targets to review the Current evolutions in the pharmacological plan of heart failure and focuses on the emerging potential therapeutic agents.
Keywords:
Global pandemic, Novel therapies, Heart failure, Left ventricular ejection fraction, Sacubitril valsartan
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References
1. Dassanayaka S., Jones S.P. Recent Developments in Heart Failure. Circ. Res. 2015;117:e58–e63.
2. Savarese G, Lund LH. Global Public Health Burden of Heart Failure. Card Fail Rev. 2017 Apr;3(1):7-11.
3. Nussbaumerová B, Rosolová H. Diagnosis of heart failure: the new classification of heart failure. Vnitr Lek. 2018 Fall;64(9):847-851.
4. Ziaeian B, Fonarow GC. Epidemiology and aetiology of heart failure. Nat Rev Cardiol. 2016 Jun;13(6):368-78.
5. Armstrong PW, Pieske B, Anstrom KJ, Ezekowitz J, Hernandez AF, Butler J, Lam CSP, Ponikowski P, Voors AA, Jia G, McNulty SE, Patel MJ, Roessig L, Koglin J, O'Connor CM., VICTORIA Study Group. Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2020 May 14;382(20):1883-1893.
6. Iacoviello M, Palazzuoli A, Gronda E. Recent advances in pharmacological treatment of heart failure. Eur J Clin Invest. 2021 Nov;51(11):e13624.
7. Ruehs H, Klein D, Frei M, Grevel J, Austin R, Becker C, Roessig L, Pieske B, Garmann D, Meyer M. Population Pharmacokinetics and Pharmacodynamics of Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction. Clin Pharmacokinet. 2021 Nov;60(11):1407-1421.
8. Sandner P, Vakalopoulos A, Hahn MG, Stasch JP, Follmann M. Soluble guanylate cyclase stimulators and their potential use: a patent review. Expert Opin Ther Pat. 2021 Mar;31(3):203-222.
9. Boettcher M, Gerisch M, Lobmeyer M, Besche N, Thomas D, Gerrits M, Lemmen J, Mueck W, Radtke M, Becker C. Metabolism and Pharmacokinetic Drug-Drug Interaction Profile of Vericiguat, A Soluble Guanylate Cyclase Stimulator: Results From Preclinical and Phase I Healthy Volunteer Studies. Clin Pharmacokinet. 2020 Nov;59(11):1407-1418.
10. Alsumali A, Lautsch D, Liu R, Patel D, Nanji S, Djatche LM. Budget Impact Analysis of Vericiguat for the Treatment of Chronic Heart Failure with Reduced Ejection Fraction Following a Worsening Event. Adv Ther. 2021 May;38(5):2631-2643.
11. Ezekowitz JA, O'Connor CM, Troughton RW, Alemayehu WG, Westerhout CM, Voors AA, Butler J, Lam CSP, Ponikowski P, Emdin M, Patel MJ, Pieske B, Roessig L, Hernandez AF, Armstrong PW. N-Terminal Pro-B-Type Natriuretic Peptide and Clinical Outcomes: Vericiguat Heart Failure With Reduced Ejection Fraction Study. JACC Heart Fail. 2020 Nov;8(11):931-939.
12. Tsai EJ, Kass DA. Cyclic GMP signaling in cardiovascular pathophysiology and therapeutics. Pharmacol Ther. 2009 Jun;122(3):216-38.
13. Armstrong PW, Lam CSP, Anstrom KJ, Ezekowitz J, Hernandez AF, O'Connor CM, Pieske B, Ponikowski P, Shah SJ, Solomon SD, Voors AA, She L, Vlajnic V, Carvalho F, Bamber L, Blaustein RO, Roessig L, Butler J., VITALITY-HFpEF Study Group. Effect of Vericiguat vs Placebo on Quality of Life in Patients With Heart Failure and Preserved Ejection Fraction: The VITALITY-HFpEF Randomized Clinical Trial. JAMA. 2020 Oct 20;324(15):1512-1521.
14. Burnett JC. Vericiguat - Another Victory for Targeting Cyclic GMP in Heart Failure. N Engl J Med. 2020 May 14;382(20):1952-1953.
15. Boettcher M, Thomas D, Mueck W, Loewen S, Arens E, Yoshikawa K, Becker C. Safety, pharmacodynamic, and pharmacokinetic characterization of vericiguat: results from six phase I studies in healthy subjects. Eur J Clin Pharmacol. 2021 Apr;77(4):527-537.
16. Murphy SP, Ibrahim NE, Januzzi JL. Heart Failure With Reduced Ejection Fraction: A Review. JAMA. 2020 Aug 04;324(5):488-504.
17. Pieske B, Anstrom KJ, et al. Vericiguat in patients with heart failure and reduced ejection fraction. N Engl J Med.2020;382:1883-1893.
18. How do different indicators of cardiac pump function impact upon the long-term prognosis of patients with chronic heart failure? Williams SG, Jackson M, Cooke GA, et al. Am Heart J. 2005;150:1–6.
19. Cardiac myosin activators for heart failure therapy: focus on omecamtiv mecarbil. Kaplinsky E, Mallarkey G. Drugs Context. 2018;7:212518.
20. Cardiac myosin activation: a potential therapeutic approach for systolic heart failure. Malik FI, Hartman JJ, Elias KA, et al. Science. 2011;331:1439–1443.
21. The molecular basis of the steep force-calcium relation in heart muscle. Sun Y-B, Irving M. J Mol Cell Cardiol. 2010;48:859–865.
22. Hypertrophic and dilated cardiomyopathy: four decades of basic research on muscle lead to potential therapeutic approaches to these devastating genetic diseases. Spudich JA. Biophys J. 2014;106:1236–1249.
23. Improvement of cardiac function by a cardiac myosin activator in conscious dogs with systolic heart failure. Shen Y-T, Malik FI, Zhao X, et al. Circulation: Heart Failure. 2010;3:522–527.
24. Teerlink JR, Diaz R, Felker GM, et al. Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure. N Engl J Med.2021;384:105-116.
25. Psotka MA, Gottlieb SS, Francis GS, et al. Cardiac calcitropes, myotropes, and mitotropes: JACC review topic of the week. J Am Coll Cardiol. 2019;73:2345-2353.
26. Malik FI, Hartman JJ, Elias KA, et al. Cardiac myosin activation: a potential therapeutic approach for systolic heart failure. Science.2011;331:1439-1443.
27. Santer R, Calado J. Familial renal glucosuria and SGLT2: from a Mendelian trait to a therapeutic target. Clin J Am Soc Nephrol. (2010) 5:133–41.
28. Gallo LA, Wright EM, Vallon V. Probing SGLT2 as a therapeutic target for diabetes: basic physiology and consequences. Diabetes Vasc Dis Res. (2015) 12:78–89.
29. Chen J, Williams S, Ho S, Loraine H, Hagan D, Whaley JM, et al. . Quantitative PCR tissue expression profiling of the human SGLT2 gene and related family members. Diabetes Ther. (2010) 1:57–92.
30. Wright EM, Hirayama BA, Loo DF. Active sugar transport in health and disease. J Intern Med. (2007) 261:32–43.
31. Bakris GL, Fonseca VA, Sharma K, Wright EM. Renal sodium-glucose transport: role in diabetes mellitus and potential clinical implications. Kidney Int. (2009) 75:1272–7.
32. Bonnet F, Scheen AJ. Effects of SGLT2 inhibitors on systemic and tissue low-grade inflammation: the potential contribution to diabetes complications and cardiovascular disease. Diabetes Metab. (2018) 44:457–64.
33. Yaribeygi H, Butler AE, Atkin SL, Katsiki N, Sahebkar A. Sodium–glucose cotransporter 2 inhibitors and inflammation in chronic kidney disease: possible molecular pathways. J Cell Physiol. (2018) 234:223–30.
34. Panchapakesan U, Pegg K, Gross S, Komala MG, Mudaliar H, Forbes J, et al. . Effects of SGLT2 inhibition in human kidney proximal tubular cells-renoprotection in diabetic nephropathy? PLoS ONE. (2013) 8:2–9.
35. Lee N, Heo YJ, Choi SE, Jeon JY, Han SJ, Kim DJ, et al. . Anti-inflammatory effects of empagliflozin and gemigliptin on LPS-stimulated macrophage via the IKK/NF- κ B, MKK7/JNK, and JAK2/STAT1 signalling pathways. J Immunol Res. (2021) 2021:9944880.
36. Takagi S, Li J, Takagaki Y, Kitada M, Nitta K, Takasu T, et al. . Ipragliflozin improves mitochondrial abnormalities in renal tubules induced by a high-fat diet. J Diabetes Investig. (2018) 9:1025–32.
37. Lee TM, Chang NC, Lin SZ. Dapagliflozin, a selective SGLT2 Inhibitor, attenuated cardiac fibrosis by regulating the macrophage polarization via STAT3 signaling in infarcted rat hearts. Free Radic Biol Med. (2017) 104:298–310.
38. Pirklbauer M, Sallaberger S, Staudinger P, Corazza U, Leierer J, Mayer G, et al. . Empagliflozin inhibits il-1β-mediated inflammatory response in human proximal tubular cells. Int J Mol Sci. (2021) 22:1–12.
39. Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383:1413-1424.
40. Anker SD, Butler J, Filippatos G, et al. Effect of empagliflozin on cardiovascular and renal outcomes in patients with heart failure by baseline diabetes status: results from the EMPEROR-reduced trial. Circulation. 2021;143:337-349.
41. Zannad F, Ferreira JP, Pocock SJ, et al. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. Lancet.2020;396:819-829.
42. Struthers AD, MacDonald TM: Review of aldosterone- and angiotensinII-induced target organ damage and prevention. Cardiovasc Res. 2004; 61(4):663–70.
43. Pitt B, Zannad F, Remme WJ, et al.: The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999; 341(10): 709–17
44. .Pitt B, Remme W, Zannad F, et al.: Eplerenone, a selective aldosteroneblocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003; 348(14): 1309–21.
45. Zannad F, Gattis Stough W, Rossignol P, et al.: Mineralocorticoid receptor antagonists for heart failure with reduced ejection fraction: integrating evidence into clinical practice. Eur Heart J. 2012; 33(22): 2782–95.
46. Butler J, Ezekowitz JA, Collins SP, et al.: Update on aldosterone antagonists use in heart failure with reduced left ventricular ejection fraction. Heart Failure Society of America Guidelines Committee. J Card Fail. 2012; 18(4): 265–81.
47. Zannad F, McMurray JJ, Krum H, et al.: Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011; 364(1): 11–21.
48. Yusuf S, Pfeffer MA, Swedberg K, et al.: Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet. 2003; 362(9386): 777–81.
49. Cleland JG, Tendera M, Adamus J, et al.: The perindopril in elderly people with chronic heart failure (PEP-CHF) study. Eur Heart J. 2006; 27(19): 2338–45.
50. Massie BM, Carson PE, McMurray JJ, et al.: Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med. 2008; 359(23): 2456–67.
51. Flather MD, Shibata MC, Coats AJ, et al.: Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J. 2005; 26(3): 215–25.
52. Ahmed A, Rich MW, Fleg JL, et al.: Effects of digoxin on morbidity and mortality in diastolic heart failure: the ancillary digitalis investigation group trial. Circulation. 2006; 114(5): 397–403.
53. Desai AS, Lewis EF, Li R, et al.: Rationale and design of the treatment of preserved cardiac function heart failure with an aldosterone antagonist trial: a randomized, controlled study of spironolactone in patients with symptomatic heart failure and preserved ejection fraction. Am Heart J. 2011; 162(6):966–972.e10.
54. Pitt B, Pfeffer MA, Assmann SF, et al.: Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014; 370(15): 1383–92.
55. Pfeffer MA, Claggett B, Assmann SF, et al.: Regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. Circulation. 2015; 131(1): 34–42.
56. Metra M, Torp-Pedersen C, Swedberg K, et al.: Influence of heart rate, blood pressure, and beta-blocker dose on outcome and the differences in outcome between carvedilol and metoprolol tartrate in patients with chronic heart failure: results from the COMET trial. Eur Heart J. 2005; 26(21): 2259–68.
57. Butler J, Arbogast PG, BeLue R, et al.: Outpatient adherence to beta-blockertherapy after acute myocardial infarction. J Am Coll Cardiol. 2002; 40(9):1589–95.
58. de Groote P, Isnard R, Assyag P, et al.: Is the gap between guidelines andclinical practice in heart failure treatment being filled? Insights from theIMPACT RECO survey. Eur J Heart Fail. 2007; 9(12): 1205–11.
59. Komajda M, Follath F, Swedberg K, et al.: The EuroHeart Failure Surveyprogramme--a survey on the quality of care among patients with heart failurein Europe. Part 2: treatment. Eur Heart J. 2003; 24(5): 464–74.
60. Borer JS, Fox K, Jaillon P, et al.: Antianginal and antiischemic effectsof ivabradine, an Ifinhibitor, in stable angina: a randomized, double-blind,multicentered, placebo-controlled trial. Circulation. 2003; 107(6): 817–23.
61. Manz M, Reuter M, Lauck G, et al.: A single intravenous dose of ivabradine,a novel If inhibitor, lowers heart rate but does not depress left ventricularfunction in patients with left ventricular dysfunction. Cardiology. 2003; 100(3):149–55.
62. Thollon C, Cambarrat C, Vian J, et al.: Electrophysiological effects of S 16257,a novel sino-atrial node modulator, on rabbit and guinea-pig cardiacpreparations: comparison with UL-FS 49. Br J Pharmacol. 1994; 112(1): 37–42.
63. Bois P, Bescond J, Renaudon B, et al.: Mode of action of bradycardic agent,S 16257, on ionic currents of rabbit sinoatrial node cells. Br J Pharmacol. 1996;118(4): 10517.
64. Simon L, Ghaleh B, Puybasset L, et al.: Coronary and hemodynamic effects of S16257, a new bradycardic agent, in resting and exercising conscious dogs. J Pharmacol Exp Ther. 1995; 275(2): 659–66.
65. Bel A, Perrault LP, Faris B, et al.: Inhibition of the pacemaker current: a bradycardic therapy for off-pump coronary operations. Ann Thorac Surg. 1998; 66(1): 148–52.
2. Savarese G, Lund LH. Global Public Health Burden of Heart Failure. Card Fail Rev. 2017 Apr;3(1):7-11.
3. Nussbaumerová B, Rosolová H. Diagnosis of heart failure: the new classification of heart failure. Vnitr Lek. 2018 Fall;64(9):847-851.
4. Ziaeian B, Fonarow GC. Epidemiology and aetiology of heart failure. Nat Rev Cardiol. 2016 Jun;13(6):368-78.
5. Armstrong PW, Pieske B, Anstrom KJ, Ezekowitz J, Hernandez AF, Butler J, Lam CSP, Ponikowski P, Voors AA, Jia G, McNulty SE, Patel MJ, Roessig L, Koglin J, O'Connor CM., VICTORIA Study Group. Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2020 May 14;382(20):1883-1893.
6. Iacoviello M, Palazzuoli A, Gronda E. Recent advances in pharmacological treatment of heart failure. Eur J Clin Invest. 2021 Nov;51(11):e13624.
7. Ruehs H, Klein D, Frei M, Grevel J, Austin R, Becker C, Roessig L, Pieske B, Garmann D, Meyer M. Population Pharmacokinetics and Pharmacodynamics of Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction. Clin Pharmacokinet. 2021 Nov;60(11):1407-1421.
8. Sandner P, Vakalopoulos A, Hahn MG, Stasch JP, Follmann M. Soluble guanylate cyclase stimulators and their potential use: a patent review. Expert Opin Ther Pat. 2021 Mar;31(3):203-222.
9. Boettcher M, Gerisch M, Lobmeyer M, Besche N, Thomas D, Gerrits M, Lemmen J, Mueck W, Radtke M, Becker C. Metabolism and Pharmacokinetic Drug-Drug Interaction Profile of Vericiguat, A Soluble Guanylate Cyclase Stimulator: Results From Preclinical and Phase I Healthy Volunteer Studies. Clin Pharmacokinet. 2020 Nov;59(11):1407-1418.
10. Alsumali A, Lautsch D, Liu R, Patel D, Nanji S, Djatche LM. Budget Impact Analysis of Vericiguat for the Treatment of Chronic Heart Failure with Reduced Ejection Fraction Following a Worsening Event. Adv Ther. 2021 May;38(5):2631-2643.
11. Ezekowitz JA, O'Connor CM, Troughton RW, Alemayehu WG, Westerhout CM, Voors AA, Butler J, Lam CSP, Ponikowski P, Emdin M, Patel MJ, Pieske B, Roessig L, Hernandez AF, Armstrong PW. N-Terminal Pro-B-Type Natriuretic Peptide and Clinical Outcomes: Vericiguat Heart Failure With Reduced Ejection Fraction Study. JACC Heart Fail. 2020 Nov;8(11):931-939.
12. Tsai EJ, Kass DA. Cyclic GMP signaling in cardiovascular pathophysiology and therapeutics. Pharmacol Ther. 2009 Jun;122(3):216-38.
13. Armstrong PW, Lam CSP, Anstrom KJ, Ezekowitz J, Hernandez AF, O'Connor CM, Pieske B, Ponikowski P, Shah SJ, Solomon SD, Voors AA, She L, Vlajnic V, Carvalho F, Bamber L, Blaustein RO, Roessig L, Butler J., VITALITY-HFpEF Study Group. Effect of Vericiguat vs Placebo on Quality of Life in Patients With Heart Failure and Preserved Ejection Fraction: The VITALITY-HFpEF Randomized Clinical Trial. JAMA. 2020 Oct 20;324(15):1512-1521.
14. Burnett JC. Vericiguat - Another Victory for Targeting Cyclic GMP in Heart Failure. N Engl J Med. 2020 May 14;382(20):1952-1953.
15. Boettcher M, Thomas D, Mueck W, Loewen S, Arens E, Yoshikawa K, Becker C. Safety, pharmacodynamic, and pharmacokinetic characterization of vericiguat: results from six phase I studies in healthy subjects. Eur J Clin Pharmacol. 2021 Apr;77(4):527-537.
16. Murphy SP, Ibrahim NE, Januzzi JL. Heart Failure With Reduced Ejection Fraction: A Review. JAMA. 2020 Aug 04;324(5):488-504.
17. Pieske B, Anstrom KJ, et al. Vericiguat in patients with heart failure and reduced ejection fraction. N Engl J Med.2020;382:1883-1893.
18. How do different indicators of cardiac pump function impact upon the long-term prognosis of patients with chronic heart failure? Williams SG, Jackson M, Cooke GA, et al. Am Heart J. 2005;150:1–6.
19. Cardiac myosin activators for heart failure therapy: focus on omecamtiv mecarbil. Kaplinsky E, Mallarkey G. Drugs Context. 2018;7:212518.
20. Cardiac myosin activation: a potential therapeutic approach for systolic heart failure. Malik FI, Hartman JJ, Elias KA, et al. Science. 2011;331:1439–1443.
21. The molecular basis of the steep force-calcium relation in heart muscle. Sun Y-B, Irving M. J Mol Cell Cardiol. 2010;48:859–865.
22. Hypertrophic and dilated cardiomyopathy: four decades of basic research on muscle lead to potential therapeutic approaches to these devastating genetic diseases. Spudich JA. Biophys J. 2014;106:1236–1249.
23. Improvement of cardiac function by a cardiac myosin activator in conscious dogs with systolic heart failure. Shen Y-T, Malik FI, Zhao X, et al. Circulation: Heart Failure. 2010;3:522–527.
24. Teerlink JR, Diaz R, Felker GM, et al. Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure. N Engl J Med.2021;384:105-116.
25. Psotka MA, Gottlieb SS, Francis GS, et al. Cardiac calcitropes, myotropes, and mitotropes: JACC review topic of the week. J Am Coll Cardiol. 2019;73:2345-2353.
26. Malik FI, Hartman JJ, Elias KA, et al. Cardiac myosin activation: a potential therapeutic approach for systolic heart failure. Science.2011;331:1439-1443.
27. Santer R, Calado J. Familial renal glucosuria and SGLT2: from a Mendelian trait to a therapeutic target. Clin J Am Soc Nephrol. (2010) 5:133–41.
28. Gallo LA, Wright EM, Vallon V. Probing SGLT2 as a therapeutic target for diabetes: basic physiology and consequences. Diabetes Vasc Dis Res. (2015) 12:78–89.
29. Chen J, Williams S, Ho S, Loraine H, Hagan D, Whaley JM, et al. . Quantitative PCR tissue expression profiling of the human SGLT2 gene and related family members. Diabetes Ther. (2010) 1:57–92.
30. Wright EM, Hirayama BA, Loo DF. Active sugar transport in health and disease. J Intern Med. (2007) 261:32–43.
31. Bakris GL, Fonseca VA, Sharma K, Wright EM. Renal sodium-glucose transport: role in diabetes mellitus and potential clinical implications. Kidney Int. (2009) 75:1272–7.
32. Bonnet F, Scheen AJ. Effects of SGLT2 inhibitors on systemic and tissue low-grade inflammation: the potential contribution to diabetes complications and cardiovascular disease. Diabetes Metab. (2018) 44:457–64.
33. Yaribeygi H, Butler AE, Atkin SL, Katsiki N, Sahebkar A. Sodium–glucose cotransporter 2 inhibitors and inflammation in chronic kidney disease: possible molecular pathways. J Cell Physiol. (2018) 234:223–30.
34. Panchapakesan U, Pegg K, Gross S, Komala MG, Mudaliar H, Forbes J, et al. . Effects of SGLT2 inhibition in human kidney proximal tubular cells-renoprotection in diabetic nephropathy? PLoS ONE. (2013) 8:2–9.
35. Lee N, Heo YJ, Choi SE, Jeon JY, Han SJ, Kim DJ, et al. . Anti-inflammatory effects of empagliflozin and gemigliptin on LPS-stimulated macrophage via the IKK/NF- κ B, MKK7/JNK, and JAK2/STAT1 signalling pathways. J Immunol Res. (2021) 2021:9944880.
36. Takagi S, Li J, Takagaki Y, Kitada M, Nitta K, Takasu T, et al. . Ipragliflozin improves mitochondrial abnormalities in renal tubules induced by a high-fat diet. J Diabetes Investig. (2018) 9:1025–32.
37. Lee TM, Chang NC, Lin SZ. Dapagliflozin, a selective SGLT2 Inhibitor, attenuated cardiac fibrosis by regulating the macrophage polarization via STAT3 signaling in infarcted rat hearts. Free Radic Biol Med. (2017) 104:298–310.
38. Pirklbauer M, Sallaberger S, Staudinger P, Corazza U, Leierer J, Mayer G, et al. . Empagliflozin inhibits il-1β-mediated inflammatory response in human proximal tubular cells. Int J Mol Sci. (2021) 22:1–12.
39. Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383:1413-1424.
40. Anker SD, Butler J, Filippatos G, et al. Effect of empagliflozin on cardiovascular and renal outcomes in patients with heart failure by baseline diabetes status: results from the EMPEROR-reduced trial. Circulation. 2021;143:337-349.
41. Zannad F, Ferreira JP, Pocock SJ, et al. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. Lancet.2020;396:819-829.
42. Struthers AD, MacDonald TM: Review of aldosterone- and angiotensinII-induced target organ damage and prevention. Cardiovasc Res. 2004; 61(4):663–70.
43. Pitt B, Zannad F, Remme WJ, et al.: The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999; 341(10): 709–17
44. .Pitt B, Remme W, Zannad F, et al.: Eplerenone, a selective aldosteroneblocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003; 348(14): 1309–21.
45. Zannad F, Gattis Stough W, Rossignol P, et al.: Mineralocorticoid receptor antagonists for heart failure with reduced ejection fraction: integrating evidence into clinical practice. Eur Heart J. 2012; 33(22): 2782–95.
46. Butler J, Ezekowitz JA, Collins SP, et al.: Update on aldosterone antagonists use in heart failure with reduced left ventricular ejection fraction. Heart Failure Society of America Guidelines Committee. J Card Fail. 2012; 18(4): 265–81.
47. Zannad F, McMurray JJ, Krum H, et al.: Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011; 364(1): 11–21.
48. Yusuf S, Pfeffer MA, Swedberg K, et al.: Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet. 2003; 362(9386): 777–81.
49. Cleland JG, Tendera M, Adamus J, et al.: The perindopril in elderly people with chronic heart failure (PEP-CHF) study. Eur Heart J. 2006; 27(19): 2338–45.
50. Massie BM, Carson PE, McMurray JJ, et al.: Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med. 2008; 359(23): 2456–67.
51. Flather MD, Shibata MC, Coats AJ, et al.: Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J. 2005; 26(3): 215–25.
52. Ahmed A, Rich MW, Fleg JL, et al.: Effects of digoxin on morbidity and mortality in diastolic heart failure: the ancillary digitalis investigation group trial. Circulation. 2006; 114(5): 397–403.
53. Desai AS, Lewis EF, Li R, et al.: Rationale and design of the treatment of preserved cardiac function heart failure with an aldosterone antagonist trial: a randomized, controlled study of spironolactone in patients with symptomatic heart failure and preserved ejection fraction. Am Heart J. 2011; 162(6):966–972.e10.
54. Pitt B, Pfeffer MA, Assmann SF, et al.: Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014; 370(15): 1383–92.
55. Pfeffer MA, Claggett B, Assmann SF, et al.: Regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. Circulation. 2015; 131(1): 34–42.
56. Metra M, Torp-Pedersen C, Swedberg K, et al.: Influence of heart rate, blood pressure, and beta-blocker dose on outcome and the differences in outcome between carvedilol and metoprolol tartrate in patients with chronic heart failure: results from the COMET trial. Eur Heart J. 2005; 26(21): 2259–68.
57. Butler J, Arbogast PG, BeLue R, et al.: Outpatient adherence to beta-blockertherapy after acute myocardial infarction. J Am Coll Cardiol. 2002; 40(9):1589–95.
58. de Groote P, Isnard R, Assyag P, et al.: Is the gap between guidelines andclinical practice in heart failure treatment being filled? Insights from theIMPACT RECO survey. Eur J Heart Fail. 2007; 9(12): 1205–11.
59. Komajda M, Follath F, Swedberg K, et al.: The EuroHeart Failure Surveyprogramme--a survey on the quality of care among patients with heart failurein Europe. Part 2: treatment. Eur Heart J. 2003; 24(5): 464–74.
60. Borer JS, Fox K, Jaillon P, et al.: Antianginal and antiischemic effectsof ivabradine, an Ifinhibitor, in stable angina: a randomized, double-blind,multicentered, placebo-controlled trial. Circulation. 2003; 107(6): 817–23.
61. Manz M, Reuter M, Lauck G, et al.: A single intravenous dose of ivabradine,a novel If inhibitor, lowers heart rate but does not depress left ventricularfunction in patients with left ventricular dysfunction. Cardiology. 2003; 100(3):149–55.
62. Thollon C, Cambarrat C, Vian J, et al.: Electrophysiological effects of S 16257,a novel sino-atrial node modulator, on rabbit and guinea-pig cardiacpreparations: comparison with UL-FS 49. Br J Pharmacol. 1994; 112(1): 37–42.
63. Bois P, Bescond J, Renaudon B, et al.: Mode of action of bradycardic agent,S 16257, on ionic currents of rabbit sinoatrial node cells. Br J Pharmacol. 1996;118(4): 10517.
64. Simon L, Ghaleh B, Puybasset L, et al.: Coronary and hemodynamic effects of S16257, a new bradycardic agent, in resting and exercising conscious dogs. J Pharmacol Exp Ther. 1995; 275(2): 659–66.
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16-04-2022
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D J, B D, V AD, A DP. The Current Evolutions in the Pharmacotherapeutic Management of Heart Failure. World Journal of Current Med and Pharm Research [Internet]. 2022Apr.16 [cited 2025Apr.26];4(2):23-8. Available from: https://wjcmpr.com/index.php/journal/article/view/211
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