Abstract
Background: Heart failure is a clinical condition with high mortality and morbidity that occurs when the heart is unable to pump enough blood to meet the metabolic demands of the body. The pharmacological management of heart failure has been revolutionized over the past decade with novel treatments.
Objective: The aim of the review is to highlight the recent pharmacological advances in the management of heart failure.
Results: Sodium-glucose cotransporter-2 inhibitor (SGLT2i), iron carboxymaltose, finerenone, omecamtiv mecarbil, and vericiguat have been shown to reduce hospitalization for heart failure. However, only SGLT2i, vericiguat, and omecamtiv mecarbil have been shown to reduce cardiovascular death. Finerenone has been shown to reduce cardiovascular events and renal adverse outcomes in patients with diabetes and kidney disease. Currently, only SGLT2i has been studied in patients beyond the heart failure with reduced ejection fraction population.
Conclusion: The current quadruple therapy in the treatment of heart failure has demonstrated a reduction in the hospitalization of patients and a decrease in mortality associated with the condition. Individualized heart failure therapy research have shown some benefit in select heart failure patients. Further research on novel therapies will help improve heart failure patient outcomes.
Graphical Abstract
[1]
McDonald M, Virani S, Chan M, et al. CCS/CHFS heart failure guidelines update: Defining a new pharmacologic standard of care for heart failure with reduced ejection fraction. Can J Cardiol 2021; 37(4): 531-46.
[http://dx.doi.org/10.1016/j.cjca.2021.01.017] [PMID: 33827756]
[http://dx.doi.org/10.1016/j.cjca.2021.01.017] [PMID: 33827756]
[2]
Lopaschuk GD, Verma S. Mechanisms of cardiovascular benefits of sodium glucose co-transporter 2 (SGLT2) inhibitors. JACC Basic Transl Sci 2020; 5(6): 632-44.
[http://dx.doi.org/10.1016/j.jacbts.2020.02.004] [PMID: 32613148]
[http://dx.doi.org/10.1016/j.jacbts.2020.02.004] [PMID: 32613148]
[3]
McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med 2019; 381(21): 1995-2008.
[http://dx.doi.org/10.1056/NEJMoa1911303] [PMID: 31535829]
[http://dx.doi.org/10.1056/NEJMoa1911303] [PMID: 31535829]
[4]
Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med 2020; 383(15): 1413-24.
[http://dx.doi.org/10.1056/NEJMoa2022190] [PMID: 32865377]
[http://dx.doi.org/10.1056/NEJMoa2022190] [PMID: 32865377]
[5]
Bhatt DL, Szarek M, Steg PG, et al. Sotagliflozin in patients with diabetes and recent worsening heart failure. N Engl J Med 2021; 384(2): 117-28.
[http://dx.doi.org/10.1056/NEJMoa2030183] [PMID: 33200892]
[http://dx.doi.org/10.1056/NEJMoa2030183] [PMID: 33200892]
[6]
Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med 2021; 385(16): 1451-61.
[http://dx.doi.org/10.1056/NEJMoa2107038] [PMID: 34449189]
[http://dx.doi.org/10.1056/NEJMoa2107038] [PMID: 34449189]
[7]
Voors AA, Angermann CE, Teerlink JR, et al. The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nat Med 2022; 28(3): 568-74.
[http://dx.doi.org/10.1038/s41591-021-01659-1] [PMID: 35228754]
[http://dx.doi.org/10.1038/s41591-021-01659-1] [PMID: 35228754]
[8]
Solomon SD, McMurray JJV, Claggett B, et al. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med 2022; 387(12): 1089-98.
[http://dx.doi.org/10.1056/NEJMoa2206286] [PMID: 36027570]
[http://dx.doi.org/10.1056/NEJMoa2206286] [PMID: 36027570]
[9]
Jhund PS, Kondo T, Butt JH, et al. Dapagliflozin across the range of ejection fraction in patients with heart failure: a patient-level, pooled meta-analysis of DAPA-HF and DELIVER. Nat Med 2022; 28(9): 1956-64.
[http://dx.doi.org/10.1038/s41591-022-01971-4] [PMID: 36030328]
[http://dx.doi.org/10.1038/s41591-022-01971-4] [PMID: 36030328]
[10]
Anand IS, Gupta P. Anemia and iron deficiency in heart failure. Circulation 2018; 138(1): 80-98.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.118.030099] [PMID: 29967232]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.118.030099] [PMID: 29967232]
[11]
Anker SD, Comin Colet J, Filippatos G, et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 2009; 361(25): 2436-48.
[http://dx.doi.org/10.1056/NEJMoa0908355] [PMID: 19920054]
[http://dx.doi.org/10.1056/NEJMoa0908355] [PMID: 19920054]
[12]
Ponikowski P, van Veldhuisen DJ, Comin-Colet J, et al. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency. Eur Heart J 2015; 36(11): 657-68.
[http://dx.doi.org/10.1093/eurheartj/ehu385] [PMID: 25176939]
[http://dx.doi.org/10.1093/eurheartj/ehu385] [PMID: 25176939]
[13]
Ponikowski P, Kirwan BA, Anker SD, et al. Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: A multicentre, double-blind, randomised, controlled trial. Lancet 2020; 396(10266): 1895-904.
[http://dx.doi.org/10.1016/S0140-6736(20)32339-4] [PMID: 33197395]
[http://dx.doi.org/10.1016/S0140-6736(20)32339-4] [PMID: 33197395]
[14]
Kalra PR, Cleland JGF, Petrie MC, et al. Intravenous ferric derisomaltose in patients with heart failure and iron deficiency in the UK (IRONMAN): An investigator-initiated, prospective, randomised, open-label, blinded-endpoint trial. Lancet 2022; 400(10369): 2199-209.
[http://dx.doi.org/10.1016/S0140-6736(22)02083-9] [PMID: 36347265]
[http://dx.doi.org/10.1016/S0140-6736(22)02083-9] [PMID: 36347265]
[15]
Mentz RJ, Ambrosy AP, Ezekowitz JA, et al. Randomized placebo-controlled trial of ferric carboxymaltose in heart failure with iron deficiency: Rationale and design. Circ Heart Fail 2021; 14(5): e008100.
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.008100] [PMID: 34003690]
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.008100] [PMID: 34003690]
[16]
Schaefer B, Tobiasch M, Wagner S, et al. Hypophosphatemia after intravenous iron therapy: Comprehensive review of clinical findings and recommendations for management. Bone 2022; 154: 116202.
[http://dx.doi.org/10.1016/j.bone.2021.116202] [PMID: 34534708]
[http://dx.doi.org/10.1016/j.bone.2021.116202] [PMID: 34534708]
[17]
Bakris GL, Agarwal R, Anker SD, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med 2020; 383(23): 2219-29.
[http://dx.doi.org/10.1056/NEJMoa2025845] [PMID: 33264825]
[http://dx.doi.org/10.1056/NEJMoa2025845] [PMID: 33264825]
[18]
Lv R, Xu L, Che L, Liu S, Wang Y, Dong B. Cardiovascular-renal protective effect and molecular mechanism of finerenone in type 2 diabetic mellitus. Front Endocrinol 2023; 14: 1125693.
[http://dx.doi.org/10.3389/fendo.2023.1125693] [PMID: 36860374]
[http://dx.doi.org/10.3389/fendo.2023.1125693] [PMID: 36860374]
[19]
Filippatos G, Anker SD, Agarwal R, et al. Finerenone reduces risk of incident heart failure in patients with chronic kidney disease and type 2 diabetes: Analyses from the FIGARO-DKD trial. Circulation 2022; 145(6): 437-47.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.121.057983] [PMID: 34775784]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.121.057983] [PMID: 34775784]
[20]
Study to Evaluate the Efficacy (Effect on Disease) and Safety of Finerenone on Morbidity. NCT04435626, 2023.
[21]
Additional studies with finerenone across a wide range of heart failure patients initiated, August 24, 2023. Available from: https://www.bayer.com/media/en-us/additional studies-with-finerenone-across-a-wide-range-of-heart-failurepatients-initiated/
[22]
Agarwal R, Joseph A, Anker SD, et al. Hyperkalemia risk with finerenone: Results from the FIDELIO-DKD Trial. J Am Soc Nephrol 2022; 33(1): 225-37.
[http://dx.doi.org/10.1681/ASN.2021070942] [PMID: 34732509]
[http://dx.doi.org/10.1681/ASN.2021070942] [PMID: 34732509]
[23]
Psotka MA, Gottlieb SS, Francis GS, et al. Cardiac calcitropes, myotropes, and mitotropes. J Am Coll Cardiol 2019; 73(18): 2345-53.
[http://dx.doi.org/10.1016/j.jacc.2019.02.051] [PMID: 31072579]
[http://dx.doi.org/10.1016/j.jacc.2019.02.051] [PMID: 31072579]
[24]
Teerlink JR, Felker GM, McMurray JJV, 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): 2895-903.
[http://dx.doi.org/10.1016/S0140-6736(16)32049-9] [PMID: 27914656]
[http://dx.doi.org/10.1016/S0140-6736(16)32049-9] [PMID: 27914656]
[25]
Teerlink JR, Diaz R, Felker GM, et al. Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure. N Engl J Med 2021; 384(2): 105-16.
[http://dx.doi.org/10.1056/NEJMoa2025797] [PMID: 33185990]
[http://dx.doi.org/10.1056/NEJMoa2025797] [PMID: 33185990]
[26]
Alqatati F, Elbahnasawy M, Bugazia S, et al. Safety and efficacy of omecamtiv mecarbil for heart failure: A systematic review and meta-analysis. Indian Heart J 2022; 74(3): 155-62.
[http://dx.doi.org/10.1016/j.ihj.2022.03.005] [PMID: 35301008]
[http://dx.doi.org/10.1016/j.ihj.2022.03.005] [PMID: 35301008]
[27]
Emdin M, Aimo A, Castiglione V, et al. Targeting cyclic guanosine monophosphate to treat heart failure. J Am Coll Cardiol 2020; 76(15): 1795-807.
[http://dx.doi.org/10.1016/j.jacc.2020.08.031] [PMID: 33032741]
[http://dx.doi.org/10.1016/j.jacc.2020.08.031] [PMID: 33032741]
[28]
Gheorghiade M, Greene SJ, Butler J, 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. JAMA 2015; 314(21): 2251-62.
[http://dx.doi.org/10.1001/jama.2015.15734] [PMID: 26547357]
[http://dx.doi.org/10.1001/jama.2015.15734] [PMID: 26547357]
[29]
Pieske B, Maggioni AP, Lam CSP, et al. Vericiguat in patients with worsening chronic heart failure and preserved ejection fraction: results of the Soluble guanylate Cyclase stimulator in heart failure patients with preserved ef (socrates-preserved) study. Eur Heart J 2017; 38(15): 1119-27.
[http://dx.doi.org/10.1093/eurheartj/ehw593] [PMID: 28369340]
[http://dx.doi.org/10.1093/eurheartj/ehw593] [PMID: 28369340]
[30]
Armstrong PW, Lam CSP, Anstrom KJ, et al. Effect of vericiguat vs. placebo on quality of life in patients with heart failure and preserved ejection fraction. JAMA 2020; 324(15): 1512-21.
[http://dx.doi.org/10.1001/jama.2020.15922] [PMID: 33079152]
[http://dx.doi.org/10.1001/jama.2020.15922] [PMID: 33079152]
[31]
Armstrong PW, Pieske B, Anstrom KJ, et al. Vericiguat in patients with heart failure and reduced ejection fraction. N Engl J Med 2020; 382(20): 1883-93.
[http://dx.doi.org/10.1056/NEJMoa1915928] [PMID: 32222134]
[http://dx.doi.org/10.1056/NEJMoa1915928] [PMID: 32222134]
[32]
Ma J, Guo S, Jiang H, Li B. Efficacy and safety of vericiguat in heart failure: A meta-analysis. J Int Med Res 2023; 51(3)
[http://dx.doi.org/10.1177/03000605231159333] [PMID: 36896460]
[http://dx.doi.org/10.1177/03000605231159333] [PMID: 36896460]
[33]
Iacoviello M, Palazzuoli A, Gronda E. Recent advances in pharmacological treatment of heart failure. Eur J Clin Invest 2021; 51(11): e13624.
[http://dx.doi.org/10.1111/eci.13624] [PMID: 34043809]
[http://dx.doi.org/10.1111/eci.13624] [PMID: 34043809]
[34]
McDonagh TA, Metra M, Adamo M, et al. Corrigendum to: 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 2021; 42(48): 4901.
[http://dx.doi.org/10.1093/eurheartj/ehab670] [PMID: 34649282]
[http://dx.doi.org/10.1093/eurheartj/ehab670] [PMID: 34649282]
