Comparative effectiveness of sacubitril/valsartan versus valsartan in patients with newly diagnosed hypertensive acute heart failure

doi:10.5246/jcps.2025.05.035

Abstract

Abstract:

In the present study, we aimed to investigate the clinical potential of sacubitril/valsartan compared with valsartan in patients with newly diagnosed hypertensive acute heart failure (H-AHF). A total of 63 patients were retrospectively enrolled from our hospital, with 32 patients assigned to the sacubitril/valsartan group and 31 patients to the valsartan group. Clinical characteristics, laboratory examinations, and echocardiographic data at baseline, during hospitalization, and follow-up were collected to assess. The results demonstrated that patients treated with sacubitril/valsartan achieved better control of systolic and diastolic blood pressures than those treated with valsartan. Sacubitril/valsartan also resulted in more significant reductions in N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hs-TnI), and creatinine, as well as an increase in estimated glomerular filtration rate (eGFR). Moreover, sacubitril/valsartan significantly improved left ventricular ejection fraction (LVEF), the E/e' ratio [the ratio between the early diastolic filling velocity (E-wave) and early diastolic mitral annular velocity (E')], and reduced left atrial dimension (LAD) and left ventricular mass index (LVMI). Additionally, sacubitril/valsartan might offer potential benefits in managing cardiac arrhythmias such as atrial fibrillation, ventricular or supraventricular premature beats, and left bundle branch block (LBBB). No fatal or nonfatal adverse effects were observed in the sacubitril/valsartan group, although one patient in the valsartan group experienced angioedema. In conclusion, after short-term administration, sacubitril/valsartan proved to be more effective than valsartan in lowering blood pressure, improving cardiac function and remodeling, and enhancing biomarker profiles. Furthermore, it had favorable effects on renal function and cardiac arrhythmias in newly diagnosed H-AHF patients.

Key words: Sacubitril/valsartan, Hypertension, Acute, Heart failure, Cardiac

Supporting:

Chengxia Gong, Hui Wang, Xiaoyun Shi, Wenwen Wang, Huiping Gong. Comparative effectiveness of sacubitril/valsartan versus valsartan in patients with newly diagnosed hypertensive acute heart failure[J]. Journal of Chinese Pharmaceutical Sciences, 2025, 34(5): 458-469.

Figures/Tables 5

Table 1. Baseline and clinical characteristics of study population.

Table 2. Inter-group comparison of changes in laboratory examination at week 1 and week 2.

Table 3. Inter-group comparison of echocardiographic analyses at week 2 and follow-up.

Table 4. Inter-group comparison of arrhythmic events at baseline and week 2.

References 43

[1]	Fuchs, F.D.; Whelton, P.K. High blood pressure and cardiovascular disease. Hypertension. 2020, 75, 285–292.
[2]	Wang, Z.W.; Chen, Z.; Zhang, L.F.; Wang, X.; Hao, G.; Zhang, Z.G.; Shao, L.; Tian, Y.; Dong, Y.; Zheng, C.Y.; Wang, J.L.; Zhu, M.L.; Weintraub, W.S.; Gao, R.L.; China Hypertension Survey Investigators. Status of hypertension in China: results from the China hypertension survey, 2012–2015. Circulation. 2018, 137, 2344–2356.
[3]	Pfeffer, M.A. Heart failure and hypertension: importance of prevention. Med. Clin. North Am. 2017, 101, 19–28.
[4]	Zhao, Y.; Oldenburg, B.; Zhao, S.Q.; Haregu, T.N.; Zhang, L.W. Temporal trends and geographic disparity in hypertension care in China. J. Epidemiol. 2020, 30, 354–361.
[5]	Messerli, F.H.; Rimoldi, S.F.; Bangalore, S. The transition from hypertension to heart failure contemporary update. JACC Heart Fail. 2017, 5, 543–551.
[6]	Viau, D.M.; Sala-Mercado, J.A.; Spranger, M.D.; O’Leary, D.S.; Levy, P.D. The pathophysiology of hypertensive acute heart failure. Heart. 2015, 101, 1861–1867.
[7]	Liu, J.X.; Uppal, S.; Patel, V. Management of acute hypertensive heart failure. Heart Fail. Clin. 2019, 15, 565–574.
[8]	Ponikowski, P.; Voors, A.A.; Anker, S.D.; Bueno, H.; Cleland, J.G.F.; Coats, A.J.S.; Falk, V.; González-Juanatey, J.R.; Harjola, V.P.; Jankowska, E.A.; Jessup, M.; Linde, C.; Nihoyannopoulos, P.; Parissis, J.T.; Pieske, B.; Riley, J.P.; Rosano, G.M.C.; Ruilope, L.M.; Ruschitzka, F.; Rutten, F.H.; van der Meer, P. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Rev. Esp. Cardiol. (Engl. Ed.) 2016, 69, 1167.
[9]	Peacock, F.; Amin, A.; Granger, C.B.; Pollack, C.V.; Levy, P.; Nowak, R.; Kleinschmidt, K.; Varon, J.; Wyman, A.; Gore, J.M. Hypertensive heart failure: patient characteristics, treatment, and outcomes. Am. J. Emerg. Med. 2011, 29, 855–862.
[10]	McMurray, J.J.V. Neprilysin inhibition to treat heart failure: a tale of science, serendipity, and second chances. Eur. J. Heart Fail. 2015, 17, 242–247.
[11]	Velazquez, E.J.; Morrow, D.A.; DeVore, A.D.; Duffy, C.I.; Ambrosy, A.P.; McCague, K.; Rocha, R.; Braunwald, E.; PIONEER-HF Investigators. Angiotensin-neprilysin inhibition in acute decompensated heart failure. N. Engl. J. Med. 2019, 380, 539–548.
[12]	Solomon, S.D.; McMurray, J.J.V.; Anand, I.S.; Ge, J.B.; Lam, C.S.P.; Maggioni, A.P.; Martinez, F.; Packer, M.; Pfeffer, M.A.; Pieske, B.; Redfield, M.M.; Rouleau, J.L.; van Veldhuisen, D.J.; Zannad, F.; Zile, M.R.; Desai, A.S.; Claggett, B.; Jhund, P.S.; Boytsov, S.A.; Comin-Colet, J.; Cleland, J.; Düngen, H.D.; Goncalvesova, E.; Katova, T.; Kerr Saraiva, J.F.; Lelonek, M.; Merkely, B.; Senni, M.; Shah, S.J.; Zhou, J.M.; Rizkala, A.R.; Gong, J.J.; Shi, V.C.; Lefkowitz, M.P.; PARAGON-HF Investigators. Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction. N. Engl. J. Med. 2019, 381, 1609–1620.
[13]	Huo, Y.; Li, W.M.; Webb, R.; Zhao, L.; Wang, Q.; Guo, W.N. Efficacy and safety of sacubitril/valsartan compared with olmesartan in Asian patients with essential hypertension: a randomized, double-blind, 8-week study. J. Clin. Hypertens. 2019, 21, 67–76.
[14]	Wang, T.D.; Tan, R.S.; Lee, H.Y.; Ihm, S.H.; Rhee, M.Y.; Tomlinson, B.; Pal, P.; Yang, F.; Hirschhorn, E.; Prescott, M.F.; Hinder, M.; Langenickel, T.H. Effects of sacubitril/valsartan (LCZ696) on natriuresis, diuresis, blood pressures, and NT-proBNP in salt-sensitive hypertension. Hypertension. 2017, 69, 32–41.
[15]	Li, Q.Q.; Li, L.N.; Wang, F.H.; Zhang, W.; Guo, Y.P.; Wang, F.Z.; Liu, Y.X.; Jia, J.Y.; Lin, S. Effect and safety of LCZ696 in the treatment of hypertension: a meta-analysis of 9 RCT studies. Medicine. 2019, 98, e16093.
[16]	Wachter, R.; Senni, M.; Belohlavek, J.; Straburzynska-Migaj, E.; Witte, K.K.; Kobalava, Z.; Fonseca, C.; Goncalvesova, E.; Cavusoglu, Y.; Fernandez, A.; Chaaban, S.; Bøhmer, E.; Pouleur, A.C.; Mueller, C.; Tribouilloy, C.; Lonn, E.; Buraiki, J.A.L.; Gniot, J.; Mozheiko, M.; Lelonek, M.; Noè, A.; Schwende, H.; Bao, W.B.; Butylin, D.; Pascual-Figal, D.; TRANSITION Investigators. Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study. Eur. J. Heart Fail. 2019, 21, 998–1007.
[17]	Carballo, D.; Stirnemann, J.; Garin, N.; Marti, C.; Serratrice, J.; Carballo, S. Eligibility for sacubitril-valsartan in patients with acute decompensated heart failure. ESC Heart Fail. 2020, 7, 1282–1290.
[18]	Oparil, S.; Acelajado, M.C.; Bakris, G.L.; Berlowitz, D.R.; Cífková, R.; Dominiczak, A.F.; Grassi, G.; Jordan, J.; Poulter, N.R.; Rodgers, A.; Whelton, P.K. Hypertension. Nat. Rev. Dis. Primers. 2018, 4, 18014.
[19]	Sarzani, R.; Spannella, F.; Giulietti, F.; Balietti, P.; Cocci, G.; Bordicchia, M. Cardiac natriuretic peptides, hypertension and cardiovascular risk. High Blood Press. Cardiovasc. Prev. 2017, 24, 115–126.
[20]	Andersen, M.B.; Simonsen, U.; Wehland, M.; Pietsch, J.; Grimm, D. LCZ696 (valsartan/sacubitril): a possible new treatment for hypertension and heart failure. Basic Clin. Pharmacol. Toxicol. 2016, 118, 14–22.
[21]	Ruilope, L.M.; Dukat, A.; Böhm, M.; Lacourcière, Y.; Gong, J.J.; Lefkowitz, M.P. Blood-pressure reduction with LCZ696, a novel dual-acting inhibitor of the angiotensin II receptor and neprilysin: a randomised, double-blind, placebo-controlled, active comparator study. Lancet. 2010, 375, 1255–1266.
[22]	Malik, A.H.; Aronow, W.S. Efficacy of sacubitril/valsartan in hypertension. Am. J. Ther. 2022, 29, e322–e333.
[23]	Gheorghiade, M.; De Luca, L.; Fonarow, G.C.; Filippatos, G.; Metra, M.; Francis, G.S. Pathophysiologic targets in the early phase of acute heart failure syndromes. Am. J. Cardiol. 2005, 96, 11–17.
[24]	Książczyk, M.; Lelonek, M. Angiotensin receptor/neprilysin inhibitor-a breakthrough in chronic heart failure therapy: summary of subanalysis on PARADIGM-HF trial findings. Heart Fail. Rev. 2020, 25, 393–402.
[25]	Mohyeldin, M.; Tavares, L.B.; Boorenie, M.; Abureesh, D.; Ejaz, S.; Durrani, L.; Khan, S. Efficacy of sacubitril/valsartan in the setting of acute heart failure: a systematic review. Cureus. 2021, 13, e18740.
[26]	González, A.; Ravassa, S.; López, B.; Moreno, M.U.; Beaumont, J.; San José, G.; Querejeta, R.; Bayés-Genís, A.; Díez, J. Myocardial remodeling in hypertension. Hypertension. 2018, 72, 549–558.
[27]	Senni, M.; Wachter, R.; Witte, K.K.; Straburzynska-Migaj, E.; Belohlavek, J.; Fonseca, C.; Mueller, C.; Lonn, E.; Chakrabarti, A.; Bao, W.B.; Noe, A.; Schwende, H.; Butylin, D.; Pascual-Figal, D.; Investigators, T. Initiation of sacubitril/valsartan shortly after hospitalisation for acutely decompensated heart failure in patients with newly diagnosed (de novo) heart failure: a subgroup analysis of the TRANSITION study. Eur. J. Heart Fail. 2020, 22, 303–312.
[28]	Zile, M.R.; Claggett, B.L.; Prescott, M.F.; McMurray, J.J.V.; Packer, M.; Rouleau, J.L.; Swedberg, K.; Desai, A.S.; Gong, J.J.; Shi, V.C.; Solomon, S.D. Prognostic implications of changes in N-terminal pro-B-type natriuretic peptide in patients with heart failure. J. Am. Coll. Cardiol. 2016, 68, 2425–2436.
[29]	Damman, K.; Gori, M.; Claggett, B.; Jhund, P.S.; Senni, M.; Lefkowitz, M.P.; Prescott, M.F.; Shi, V.C.; Rouleau, J.L.; Swedberg, K.; Zile, M.R.; Packer, M.; Desai, A.S.; Solomon, S.D.; McMurray, J.J.V. Renal effects and associated outcomes during angiotensin-neprilysin inhibition in heart failure. JACC Heart Fail. 2018, 6, 489–498.
[30]	Mc Causland, F.R.; Lefkowitz, M.P.; Claggett, B.; Anavekar, N.S.; Senni, M.; Gori, M.; Jhund, P.S.; McGrath, M.M.; Packer, M.; Shi, V.; Van Veldhuisen, D.J.; Zannad, F.; Comin-Colet, J.; Pfeffer, M.A.; McMurray, J.J.V.; Solomon, S.D. Angiotensin-neprilysin inhibition and renal outcomes in heart failure with preserved ejection fraction. Circulation. 2020, 142, 1236–1245.
[31]	Ito, S.; Satoh, M.; Tamaki, Y.; Gotou, H.; Charney, A.; Okino, N.; Akahori, M.; Zhang, J. Safety and efficacy of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Japanese patients with hypertension and renal dysfunction. Hypertens. Res. 2015, 38, 269–275.
[32]	Higuchi, S.; Kabeya, Y.; Matsushita, K.; Yamasaki, S.; Ohnishi, H.; Yoshino, H. Urinary cast is a useful predictor of acute kidney injury in acute heart failure. Sci. Rep. 2019, 9, 4352.
[33]	Levine, Y.C.; Rosenberg, M.A.; Mittleman, M.; Samuel, M.; Methachittiphan, N.; Link, M.; Josephson, M.E.; Buxton, A.E. B-type natriuretic peptide is a major predictor of ventricular tachyarrhythmias. Heart Rhythm. 2014, 11, 1109–1116.
[34]	Alvarez, C.K.; Cronin, E.; Baker, W.L.; Kluger, J. Heart failure as a substrate and trigger for ventricular tachycardia. J. Interv. Card. Electrophysiol. 2019, 56, 229–247.
[35]	de Diego, C.; González-Torres, L.; Núñez, J.M.; Centurión Inda, R.; Martin-Langerwerf, D.A.; Sangio, A.D.; Chochowski, P.; Casasnovas, P.; Blazquéz, J.C.; Almendral, J. Effects of angiotensin-neprilysin inhibition compared to angiotensin inhibition on ventricular arrhythmias in reduced ejection fraction patients under continuous remote monitoring of implantable defibrillator devices. Heart Rhythm. 2018, 15, 395–402.
[36]	Martens, P.; Nuyens, D.; Rivero-Ayerza, M.; Van Herendael, H.; Vercammen, J.; Ceyssens, W.; Luwel, E.; Dupont, M.; Mullens, W. Sacubitril/valsartan reduces ventricular arrhythmias in parallel with left ventricular reverse remodeling in heart failure with reduced ejection fraction. Clin. Res. Cardiol. 2019, 108, 1074–1082.
[37]	Valentim Gonçalves, A.; Pereira-da-Silva, T.; Galrinho, A.; Rio, P.; Moura Branco, L.; Soares, R.; Feliciano, J.; Ilhão Moreira, R.; Cruz Ferreira, R. Antiarrhythmic effect of sacubitril-valsartan: cause or consequence of clinical improvement? J. Clin. Med. 2019, 8, 869.
[38]	Mohammad, Z.; Ahmad, J.; Sultan, A.; Penagaluri, A.; Morin, D.; Dominic, P. Effect of sacubitril-valsartan on the incidence of atrial fibrillation: a meta-analysis. J. Cardiovasc. Electrophysiol. 2023, 34, 1037–1042.
[39]	Mujadzic, H.; Prousi, G.S.; Napier, R.; Siddique, S.; Zaman, N. The impact of angiotensin receptor-neprilysin inhibitors on arrhythmias in patients with heart failure: a systematic review and meta-analysis. J. Innov. Card. Rhythm Manag. 2022, 13, 5164–5175.
[40]	Iwasaki, Y.K.; Nishida, K.; Kato, T.; Nattel, S. Atrial fibrillation pathophysiology: implications for management. Circulation. 2011, 124, 2264–2274.
[41]	Karaliute, R.; Jureviciute, J.; Jurgaityte, J.; Stanaitiene, G.; Mizariene, V.; Kazakevicius, T.; Urboniene, D.; Kavoliuniene, A. Relationship of natriuretic peptides with left atrial structure and function within 1 month after electrical cardioversion in patients with persistent atrial fibrillation. Biomed Res. Int. 2019, 2019, 7636195.
[42]	Li, L.Y.F.; Lou, Q.; Liu, G.Z.; Lv, J.C.; Yun, F.X.; Li, T.K.; Yang, W.; Zhao, H.Y.; Zhang, L.; Bai, N.; Zhan, C.C.; Yu, J.; Zang, Y.X.; Li, W.M. Sacubitril/valsartan attenuates atrial electrical and structural remodelling in a rabbit model of atrial fibrillation. Eur. J. Pharmacol. 2020, 881, 173120.
[43]	Wang, Z.; Taylor, L.K.; Denney, W.D.; Hansen, D.E. Initiation of ventricular extrasystoles by myocardial stretch in chronically dilated and failing canine left ventricle. Circulation. 1994, 90, 2022–2031.