Effect of Angiotensin Receptor-Neprilysin Inhibitor versus Valsartan on Cardiac Status in Patients with Chronic Heart Failure with Reduced Ejection Fraction: A Randomized Clinical Trial in Rangpur Medical College Hospital, Bangladesh
Background: Heart failure with reduced ejection fraction has a significant association with considerable morbidity and mortality, but there is still inadequacy in appropriate treatment to prevent this condition. We observed the effect of angiotensin receptor neprilysin inhibitor (ARNi) with such disorder compared to valsartan. Methods: In this single-blind trial, the patients were enrolled with chronic HF aged on or above 40 years, symptomatic NYHA class II - IV, an elevated NT-proBNP above 400 pg/ml level and a reduced LVEF of 40% or less. The patients were randomly assigned 1:1 to the treatment arms either ARNi (50 mg titrated to 100 mg twice a day) or valsartan (40 mg titrated to 80 mg twice a day) and followed for a median of 88 days. The primary outcome was mode of cardiovascular death and re-hospitalization for heart failure. Changes in the level of NT-proBNP and rate of ejection fraction were also measured. Results: Cardiovascular deaths occurred 4 (8%) in the ARNi treatment arm, while 11 (22%) in the valsartan treatment arm with significant hazard ratio in the ARNi group [Hazard Ratio = 0.37; 95% CI: 0.34, 0.64; p = 0.042] during a median of 88 days of follow up period and 2 (4%) of the patients from the ARNi treatment arm were hospitalized due to HF, while in the valsartan treatment arm, 10 (20%) patients were hospitalized due to HF followed by receiving treatment respectively with hazard ratio in the ARNi group [Hazard Ratio = 0.80; 95% CI: 0.57, 0.92; p < 0.037]. Furthermore, a significant effect was found to have in LVEF and NT-proBNP at 95% level of significance (p < 0.05). These effects resulted from somewhat increased in LVEF (30.4% ± 6.7% to 38.8% ± 8.1%) and intensely decreased in NT-proBNP (3066.5 ± 1882.1 pg/ml to 808.2 ± 592.5 pg/ml) in the ARNi group, as compared to valsartan group in LVEF (30.6% ± 6.0% to 35% ± 7.9%) and in NT-proBNP (3488.2 ± 2912.2 pg/ml to 1886.4 ± 1017.8 pg/ml). Conclusion: Chronic treatment with the angiotensin receptor neprilysin inhibitor (ARNi) strongly decreases the NT-proBNP as well as morbidity and mortality and increases LVEF in patients with heart failure compared to valsartan.
References
[1]
Ho, K.K.L., Pinsky, J.L., Kannel, W.B. and Levy, D. (1993) The Epidemiology of Heart Failure: The Framingham Study. Journal of the American College of Cardiology, 22, 6A-13A. https://doi.org/10.1016/0735-1097(93)90455-A
[2]
Go, A.S., et al. (2013) Heart Disease and Stroke Statistics 2013 Update: A Report from the American Heart Association. Circulation, 127, e6-e245. http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=emed11&NEWS=N&AN=2013022804
[3]
Savarese, G. and Lund, L.H. (2017) Global Public Health Burden of Heart Failure. Cardiac Failure Review, 3, 7-11. https://doi.org/10.15420/cfr.2016:25:2
[4]
Fonarow, G.C., et al. (2007) Characteristics, Treatments, and Outcomes of Patients with Preserved Systolic Function Hospitalized for Heart Failure: A Report from the OPTIMIZE-HF Registry. Journal of the American College of Cardiology, 50, 768-777.
[5]
Bhatia, R.S., Tu, J.V., Lee, D.S., Austin, P.C., Fang, J., Haouzi, A., et al. (2006) Outcome of Heart Failure with Preserved Ejection Fraction in a Population-Based Study. The New England Journal of Medicine, 355, 260-269. https://doi.org/10.1056/NEJMoa051530
[6]
Owan, T.E., Hodge, D.O., Herges, R.M., Jacobsen, S.J., Roger, V.L. and Redfield, M.M. (2006) Trends in Prevalence and Outcome of Heart Failure with Preserved Ejection Fraction. The New England Journal of Medicine, 355, 251-259. https://doi.org/10.1056/NEJMoa052256
[7]
Aronow, W.S., Ahn, C. and Kronzon, I. (1997) Effect of Propranolol versus No Propranolol on Total Mortality plus Nonfatal Myocardial Infarction in Older Patients with Prior Myocardial Infarction, Congestive Heart Failure, and Left Ventricular Ejection Fraction ≤ 40% Treated with Diuretics plus Angiot. American Journal of Cardiology, 80, 207-209. https://doi.org/10.1016/S0002-9149(97)00320-2
[8]
Setaro, J.F., Zaret, B.L., Schulman, D.S., Black, H.R. and Soufer, R. (1990) Usefulness of Verapamil for Congestive Heart Failure Associated with Abnormal Left Ventricular Diastolic Filling and Normal Left Ventricular Systolic Performance. American Journal of Cardiology, 66, 981-986. https://doi.org/10.1016/0002-9149(90)90937-V
[9]
Cleland, J.G.F., Tendera, M., Adamus, J., Freemantle, N., Polonski, L. and Taylor, J. (2006) The Perindopril in Elderly People with Chronic Heart Failure (PEP-CHF) Study. European Heart Journal, 27, 2338-2345. http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=emed7&NEWS=N&AN=2006472683
[10]
Yusuf, S., Pfeffer, M.A., Swedberg, K., Granger, C.B., Held, P., McMurray, J.J.V., et al. (2003) Effects of Candesartan in Patients with Chronic Heart Failure and Preserved Left-Ventricular Ejection Fraction: The CHARM-Preserved Trial. The Lancet, 362, 777-781. https://doi.org/10.1016/S0140-6736(03)14285-7
[11]
Members, A.F., McMurray, J.J.V., Adamopoulos, S., Anker, S.D., Auricchio, A., Bohm, M., et al. (2012) ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in Collaboration with the Heart. European Heart Journal, 33, 1787-1847. http://eurheartj.oxfordjournals.org/cgi/doi/10.1093/eurheartj/ehs104
[12]
Gu, J., Noe, A., Chandra, P., Al-Fayoumi, S., Ligueros-Saylan, M., Sarangapani, R., et al. (2010) Pharmacokinetics and Pharmacodynamics of LCZ696, a Novel Dual-Acting Angiotensin Receptor-Neprilysin Inhibitor (ARNi). The Journal of Clinical Pharmacology, 50, 401-414. https://doi.org/10.1177/0091270009343932
[13]
Martinez-Rumayor, A., Richards, A.M., Burnett, J.C. and Januzzi, J.L. (2008) Biology of the Natriuretic Peptides. American Journal of Cardiology, 101, 3-8. https://doi.org/10.1016/j.amjcard.2007.11.012
[14]
Potter, L.R., Abbey-Hosch, S. and Dickey, D.M. (2006) Natriuretic Peptides, Their Receptors, and Cyclic Guanosine Monophosphate-Dependent Signaling Functions. Endocrine Reviews, 27, 47-72. https://doi.org/10.1210/er.2005-0014
[15]
Gardner, D.G., Chen, S., Glenn, D.J. and Grigsby, C.L. (2007) Molecular Biology of the Natriuretic Peptide System: Implications for Physiology and Hypertension. Hypertension, 49, 419-426. https://doi.org/10.1161/01.HYP.0000258532.07418.fa
[16]
Fryer, R.M., Segreti, J., Banfor, P.N., Widomski, D.L., Backes, B.J., Lin, C.W., et al. (2008) Effect of Bradykinin Metabolism Inhibitors on Evoked Hypotension in Rats: Rank Efficacy of Enzymes Associated with Bradykinin-Mediated Angioedema. British Journal of Pharmacology, 153, 947-955. https://doi.org/10.1038/sj.bjp.0707641
[17]
Kostis, J.B., Packer, M., Black, H.R., Schmieder, R., Henry, D. and Levy, E. (2004) Omapatrilat and Enalapril in Patients with Hypertension: The Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) Trial. American Journal of Hypertension, 17, 103-111. https://doi.org/10.1016/j.amjhyper.2003.09.014
[18]
Ruilope, L.M., Dukat, A., Böhm, M., Lacourcière, Y., Gong, J. and Lefkowitz, M.P. (2010) Blood-Pressure Reduction with LCZ696, a Novel Dual-Acting Inhibitor of the Angiotensin II Receptor and Neprilysin: A Randomised, Double-Blind, Place-bo-Controlled, Active Comparator Study. The Lancet, 375, 1255-1266. https://doi.org/10.1016/S0140-6736(09)61966-8
[19]
Nishimura, R.A., Otto, C.M., Bonow, R.O., Carabello, B.A., Erwin, J.P., Fleisher, L.A., et al. (2017) AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Journal of the American College of Cardiology, 70, 252-289. https://doi.org/10.1016/j.jacc.2017.03.011
[20]
Packer, M. (2001) Proposal for a New Clinical End Point to Evaluate the Efficacy of Drugs and Devices in the Treatment of Chronic Heart Failure. Journal of Cardiac Failure, 7, 176-182. https://doi.org/10.1054/jcaf.2001.25652
[21]
Swedberg, K. and Kjekshus, J. (1988) Effects of Enalapril on Mortality in Severe Congestive Heart Failure: Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). American Journal of Cardiology, 62, 60A-66A. https://doi.org/10.1016/S0002-9149(88)80087-0
[22]
Yusuf, S. (1991) Effect of Enalapril on Survival in Patients with Reduced Left Ventricular Ejection Fractions and Congestive Heart Failure. Annals of Internal Medicine, 115, 67.
[23]
Brown, E.J., Chew, P.H., MacLean, A., Gelperin, K., Ilgenfritz, J.P. and Blumenthal, M. (1995) Effects of Fosinopril on Exercise Tolerance and Clinical Deterioration in Patients with Chronic Congestive Heart Failure Not Taking Digitalis. American Journal of Cardiology, 75, 596-600. https://doi.org/10.1016/S0002-9149(99)80624-9
[24]
Rogers, J.K., et al. (2012) Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms: Analysis of Repeat Hospitalizations. Circulation, 126, 2317-2323. http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L52252730 https://doi.org/10.1161/CIRCULATIONAHA.112.110536
[25]
Aurigemma, G.P. and Gaasch, W.H. (2004) Clinical Practice. Diastolic Heart Failure. The New England Journal of Medicine, 351, 1097-1105. https://doi.org/10.1056/NEJMcp022709
[26]
McMurray, J.J., Adamopoulos, S., Anker, S.D., et al. (2012) ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in Collaboration with the Heart Failure Association (HFA) of the ESC. European Heart Journal, 33, 1787-1847.
[27]
Alehagen, U., Svensson, E. and Dahlström, U. (2007) Natriuretic Peptide Biomarkers as Information Indicators in Elderly Patients with Possible Heart Failure Followed over Six Years: A Head-to-Head Comparison of Four Cardiac Natriuretic Peptides. Journal of Cardiac Failure, 13, 452-461. https://doi.org/10.1016/j.cardfail.2007.03.002
[28]
Rademaker, M.T., Charles, C.J., Espiner, E.A., Nicholls, M.G., Richards, A.M. and Kosoglou, T. (1998) Combined Neutral Endopeptidase and Angiotensin-Converting Enzyme Inhibition in Heart Failure: Role of Natriuretic Peptides and Angiotensin II. Journal of Cardiovascular Pharmacology, 31, 116-125. https://doi.org/10.1097/00005344-199801000-00017
[29]
Packer, M., et al. (2002) Comparison of Omapatrilat and Enalapril in Patients with Chronic Heart Failure: The Omapatrilat versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE). Circulation, 106, 920-926. https://doi.org/10.1161/01.CIR.0000029801.86489.50 http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=emed5&NEWS=N&AN=2002303897
[30]
Damman, K., Gori, M., Claggett, B., Jhund, P.S., Senni, M., Lefkowitz, M.P., et al. (2018) Renal Effects and Associated Outcomes during Angiotensin-Neprilysin Inhibition in Heart Failure. JACC: Heart Failure, 6, 489-498. https://doi.org/10.1016/j.jchf.2018.02.004