NT-proBNP Response to Sacubitril/Valsartan in Hospitalized Heart Failure Patients With Reduced Ejection Fraction: TRANSITION Study

Pascual-Figal, D.; Wachter, R.; Senni, M.; Bao, W.; Noe, A.; Schwende, H.; Butylin, D.; Prescott, M.F.; Gniot, J.; Mozheiko, M.; Lelonek, M.; Dominguez, A.R.; Horacek, T.; Garcia del Rio, E.; Kobalava, Z.; Mueller, C.E.; Cavusoglu, Y.; Straburzynska-Migaj, E.; Slanina, M.; vom Dahl, J.; Ryding, A.; Moriarty, A.; Robles, M.B.; Villota, J.N.; Quintana, A.G.; Nitschke, T.; Garcia Pinilla, J.M.; Bonet, L.A.; Chaaban, S.; Filali zaatari, S.; Spinar, J.; Musial, W.; Abdelbaki, K.; Belohlavek, J.; Fehske, W.; Bott, M.C.; Hoegalmen, G.; Leiro, M.C.; Ozcan, I.T.; Mullens, W.; Kryza, R.; Al-Ani, R.; Loboz-Grudzien, K.; Ermoshkina, L.; Hojerova, S.; Fernandez, A.A.; Spinarova, L.; Lapp, H.; Bulut, E.; Almeida, F.; Vishnevsky, A.; Belicova, M.; Pascual, D.; Witte, K.; Wong, K.; Droogne, W.; Delforge, M.; Peterka, M.; Olbrich, H.-.; Carugo, S.; Nessler, J.; Mcgill, T.H.; Huegl, B.; Akin, I.; Moreira, I.; Baglikov, A.; Thambyrajah, J.; Hayes, C.; Barrionuevo, M.R.; Yigit, Z.; Kaya, H.; Klimsa, Z.; Radvan, M.; Kadel, C.; Landmesser, U.; Di Tano, G.; Lisik, M.B.; Fonseca, C.; Oliveira, L.; Marques, I.; Santos, L.M.; Lenner, E.; Letavay, P.; Bueno, M.G.; Mota, P.; Wong, A.; Bailey, K.; Foley, P.; Hasbani, E.; Virani, S.; Massih, T.A.; Al-Saif, S.; Taborsky, M.; Kaislerova, M.; Motovska, Z.; Cohen, A.A.; Logeart, D.; Endemann, D.; Ferreira, D.; Brito, D.; Kycina, P.; Bollano, E.; Basilio, E.G.; Rubio, L.F.; Aguado, M.G.; Schiavi, L.B.; Zivano, D.F.; Lonn, E.; El Sayed, A.; Pouleur, A.-.; Heyse, A.; Schee, A.; Polasek, R.; Houra, M.; Tribouilloy, C.; Seronde, M.F.; Galinier, M.; Noutsias, M.; Schwimmbeck, P.; Voigt, I.; Westermann, D.; Pulignano, G.; Vegsundvaag, J.; Da Silva Antunes, J.A.; Monteiro, P.; Stevlik, J.; Goncalvesova, E.; Hulkoova, B.; Castro Fernandez, A.J.; Davies, C.; Squire, I.; Meyer, P.; Sheppard, R.; Sahin, T.; Sochor, K.; De Geeter, G.; Schmeisser, A.; Weil, J.; Soares, A.O.; Vasilevna, O.B.; Oshurkov, A.; Sunderland, S.J.; Glover, J.; Exequiel, T.; Decoulx, E.; Meyer, S.; Muenzel, T.; Frioes, F.; Arbolishvili, G.; Tokarcikova, A.; Karlstrom, P.; Trullas Vila, J.C.; Perez, G.P.; Sankaranarayanan, R.; Nageh, T.; Alasia, D.C.; Refaat, M.; Demirkan, B.; Al-Buraiki, J.; Karabsheh, S.

doi:10.1016/j.jchf.2020.05.012

Objectives: This study examined the effects of sacubitril/valsartan on N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels and determined patient characteristics associated with favorable NT-proBNP reduction response. Background: NT-proBNP levels reflect cardiac wall stress and predict event risk in patients with acute decompensated heart failure (ADHF). Methods: Post-hoc analysis of the TRANSITION (Comparison of Pre- and Post-discharge Initiation of Sacubitril/Valsartan Therapy in HFrEF Patients After an Acute Decompensation Event) study, including stabilized ADHF patients with reduced ejection fraction, randomized to open-label sacubitril/valsartan initiation in-hospital (pre-discharge) versus post-discharge. NT-proBNP was measured at randomization (baseline), discharge, and 4 and 10 weeks post-randomization. A favorable NT-proBNP response was defined as reduction to ≤1,000 pg/ml or >30% from baseline. Results: In patients receiving sacubitril/valsartan in-hospital, NT-proBNP was reduced by 28% at discharge, with 46% of patients obtaining favorable NT-proBNP reduction response compared with a 4% reduction and 18% favorable response rate in patients initiated post-discharge (p < 0.001). NT-proBNP was reduced similarly in patients initiating sacubitril/valsartan pre- and post-discharge (reduction at 4 weeks: 25%/22%; 10 weeks: 38%/34%) with comparable favorable response rates (46%/42% and 51%/48% at 4 and 10 weeks, respectively). NT-proBNP favorable response at 4 weeks was associated with lower risk of first heart failure (HF) rehospitalization or cardiovascular death through 26 weeks (hazard ratio: 0.57; 95% confidence interval [CI]: 0.38 to 0.86; p = 0.007). Predictors of a favorable response at 4 weeks were starting dose ≥49/51 mg twice daily, higher baseline NT-proBNP, lower baseline serum creatinine, de novo HF, no atrial fibrillation, angiotensin-converting enzyme inhibitor–naive or angiotensin receptor blocker–naive, and no prior myocardial infarction. Conclusions: In-hospital initiation of sacubitril/valsartan produced rapid reductions in NT-proBNP, statistically significant at discharge. A favorable NT-proBNP response over time was associated with a better prognosis and predicted by higher starting dose and predisposing clinical profile. (Comparison of Pre- and Post-discharge Initiation of LCZ696 Therapy in HFrEF Patients After an Acute Decompensation Event [TRANSITION]; NCT02661217)

NT-proBNP Response to Sacubitril/Valsartan in Hospitalized Heart Failure Patients With Reduced Ejection Fraction: TRANSITION Study / D. Pascual-Figal, R. Wachter, M. Senni, W. Bao, A. Noe, H. Schwende, D. Butylin, M.F. Prescott, J. Gniot, M. Mozheiko, M. Lelonek, A.R. Dominguez, T. Horacek, E. Garcia del Rio, Z. Kobalava, C.E. Mueller, Y. Cavusoglu, E. Straburzynska-Migaj, M. Slanina, J. vom Dahl, A. Ryding, A. Moriarty, M.B. Robles, J.N. Villota, A.G. Quintana, T. Nitschke, J.M. Garcia Pinilla, L.A. Bonet, S. Chaaban, S. Filali zaatari, J. Spinar, W. Musial, K. Abdelbaki, J. Belohlavek, W. Fehske, M.C. Bott, G. Hoegalmen, M.C. Leiro, I.T. Ozcan, W. Mullens, R. Kryza, R. Al-Ani, K. Loboz-Grudzien, L. Ermoshkina, S. Hojerova, A.A. Fernandez, L. Spinarova, H. Lapp, E. Bulut, F. Almeida, A. Vishnevsky, M. Belicova, D. Pascual, K. Witte, K. Wong, W. Droogne, M. Delforge, M. Peterka, H.-. Olbrich, S. Carugo, J. Nessler, T.H. McGill, B. Huegl, I. Akin, I. Moreira, A. Baglikov, J. Thambyrajah, C. Hayes, M.R. Barrionuevo, Z. Yigit, H. Kaya, Z. Klimsa, M. Radvan, C. Kadel, U. Landmesser, G. Di Tano, M.B. Lisik, C. Fonseca, L. Oliveira, I. Marques, L.M. Santos, E. Lenner, P. Letavay, M.G. Bueno, P. Mota, A. Wong, K. Bailey, P. Foley, E. Hasbani, S. Virani, T.A. Massih, S. Al-Saif, M. Taborsky, M. Kaislerova, Z. Motovska, A.A. Cohen, D. Logeart, D. Endemann, D. Ferreira, D. Brito, P. Kycina, E. Bollano, E.G. Basilio, L.F. Rubio, M.G. Aguado, L.B. Schiavi, D.F. Zivano, E. Lonn, A. El Sayed, A.-. Pouleur, A. Heyse, A. Schee, R. Polasek, M. Houra, C. Tribouilloy, M.F. Seronde, M. Galinier, M. Noutsias, P. Schwimmbeck, I. Voigt, D. Westermann, G. Pulignano, J. Vegsundvaag, J.A. Da Silva Antunes, P. Monteiro, J. Stevlik, E. Goncalvesova, B. Hulkoova, A.J. Castro Fernandez, C. Davies, I. Squire, P. Meyer, R. Sheppard, T. Sahin, K. Sochor, G. De Geeter, A. Schmeisser, J. Weil, A.O. Soares, O.B. Vasilevna, A. Oshurkov, S.J. Sunderland, J. Glover, T. Exequiel, E. Decoulx, S. Meyer, T. Muenzel, F. Frioes, G. Arbolishvili, A. Tokarcikova, P. Karlstrom, J.C. Trullas Vila, G.P. Perez, R. Sankaranarayanan, T. Nageh, D.C. Alasia, M. Refaat, B. Demirkan, J. Al-Buraiki, S. Karabsheh. - In: JACC. HEART FAILURE. - ISSN 2213-1779. - 8:10(2020 Oct), pp. 822-833. [10.1016/j.jchf.2020.05.012]

NT-proBNP Response to Sacubitril/Valsartan in Hospitalized Heart Failure Patients With Reduced Ejection Fraction: TRANSITION Study

Pascual-Figal D.;Wachter R.;Senni M.;W. Bao;Noe A.;Schwende H.;Butylin D.;Prescott M. F.;Gniot J.;Mozheiko M.;Lelonek M.;Dominguez A. R.;Horacek T.;Garcia del Rio E.;Kobalava Z.;Mueller C. E.;Cavusoglu Y.;Straburzynska-Migaj E.;Slanina M.;vom Dahl J.;Ryding A.;Moriarty A.;Robles M. B.;Villota J. N.;Quintana A. G.;Nitschke T.;Garcia Pinilla J. M.;Bonet L. A.;Chaaban S.;Filali zaatari S.;Spinar J.;Musial W.;Abdelbaki K.;Belohlavek J.;Fehske W.;Bott M. C.;Hoegalmen G.;Leiro M. C.;Ozcan I. T.;Mullens W.;Kryza R.;Al-Ani R.;Loboz-Grudzien K.;Ermoshkina L.;Hojerova S.;Fernandez A. A.;Spinarova L.;Lapp H.;Bulut E.;Almeida F.;Vishnevsky A.;Belicova M.;Pascual D.;Witte K.;Wong K.;Droogne W.;Delforge M.;Peterka M.;Olbrich H. -G.;S. Carugo;Nessler J.;McGill T. H.;Huegl B.;Akin I.;Moreira I.;Baglikov A.;Thambyrajah J.;Hayes C.;Barrionuevo M. R.;Yigit Z.;Kaya H.;Klimsa Z.;Radvan M.;Kadel C.;Landmesser U.;Di Tano G.;Lisik M. B.;Fonseca C.;Oliveira L.;Marques I.;Santos L. M.;Lenner E.;Letavay P.;Bueno M. G.;Mota P.;Wong A.;Bailey K.;Foley P.;Hasbani E.;Virani S.;Massih T. A.;Al-Saif S.;Taborsky M.;Kaislerova M.;Motovska Z.;Cohen A. A.;Logeart D.;Endemann D.;Ferreira D.;Brito D.;Kycina P.;Bollano E.;Basilio E. G.;Rubio L. F.;Aguado M. G.;Schiavi L. B.;Zivano D. F.;Lonn E.;El Sayed A.;Pouleur A. -C.;Heyse A.;Schee A.;Polasek R.;Houra M.;Tribouilloy C.;Seronde M. F.;Galinier M.;Noutsias M.;Schwimmbeck P.;Voigt I.;Westermann D.;Pulignano G.;Vegsundvaag J.;Da Silva Antunes J. A.;Monteiro P.;Stevlik J.;Goncalvesova E.;Hulkoova B.;Castro Fernandez A. J.;Davies C.;Squire I.;Meyer P.;Sheppard R.;Sahin T.;Sochor K.;De Geeter G.;Schmeisser A.;Weil J.;Soares A. O.;Vasilevna O. B.;Oshurkov A.;Sunderland S. J.;Glover J.;Exequiel T.;Decoulx E.;Meyer S.;Muenzel T.;Frioes F.;Arbolishvili G.;Tokarcikova A.;Karlstrom P.;Trullas Vila J. C.;Perez G. P.;Sankaranarayanan R.;Nageh T.;Alasia D. C.;Refaat M.;Demirkan B.;Al-Buraiki J.;Karabsheh S.

2020

Abstract

Objectives: This study examined the effects of sacubitril/valsartan on N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels and determined patient characteristics associated with favorable NT-proBNP reduction response. Background: NT-proBNP levels reflect cardiac wall stress and predict event risk in patients with acute decompensated heart failure (ADHF). Methods: Post-hoc analysis of the TRANSITION (Comparison of Pre- and Post-discharge Initiation of Sacubitril/Valsartan Therapy in HFrEF Patients After an Acute Decompensation Event) study, including stabilized ADHF patients with reduced ejection fraction, randomized to open-label sacubitril/valsartan initiation in-hospital (pre-discharge) versus post-discharge. NT-proBNP was measured at randomization (baseline), discharge, and 4 and 10 weeks post-randomization. A favorable NT-proBNP response was defined as reduction to ≤1,000 pg/ml or >30% from baseline. Results: In patients receiving sacubitril/valsartan in-hospital, NT-proBNP was reduced by 28% at discharge, with 46% of patients obtaining favorable NT-proBNP reduction response compared with a 4% reduction and 18% favorable response rate in patients initiated post-discharge (p < 0.001). NT-proBNP was reduced similarly in patients initiating sacubitril/valsartan pre- and post-discharge (reduction at 4 weeks: 25%/22%; 10 weeks: 38%/34%) with comparable favorable response rates (46%/42% and 51%/48% at 4 and 10 weeks, respectively). NT-proBNP favorable response at 4 weeks was associated with lower risk of first heart failure (HF) rehospitalization or cardiovascular death through 26 weeks (hazard ratio: 0.57; 95% confidence interval [CI]: 0.38 to 0.86; p = 0.007). Predictors of a favorable response at 4 weeks were starting dose ≥49/51 mg twice daily, higher baseline NT-proBNP, lower baseline serum creatinine, de novo HF, no atrial fibrillation, angiotensin-converting enzyme inhibitor–naive or angiotensin receptor blocker–naive, and no prior myocardial infarction. Conclusions: In-hospital initiation of sacubitril/valsartan produced rapid reductions in NT-proBNP, statistically significant at discharge. A favorable NT-proBNP response over time was associated with a better prognosis and predicted by higher starting dose and predisposing clinical profile. (Comparison of Pre- and Post-discharge Initiation of LCZ696 Therapy in HFrEF Patients After an Acute Decompensation Event [TRANSITION]; NCT02661217)

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Scheda completa (DC)

	Parole chiave
	
			acute decompensated heart failure; heart failure with reduced ejection fraction; N-terminal pro–B-type natriuretic peptide; sacubitril/valsartan; TRANSITION study
		
	Settori scientifico-disciplinari dell'articolo
	
			Settore MED/11 - Malattie dell'Apparato Cardiovascolare
		
	Data di pubblicazione
	
			ott-2020
		
	Rivista in ANCE
	
			JACC. HEART FAILURE
		
	DOI
	
			https://dx.doi.org/10.1016/j.jchf.2020.05.012
		
	Tipologia
	
			Article (author)
		
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			01 - Articolo su periodico

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