NT-proBNP Response to Sacubitril/Valsartan in Hospitalized Heart Failure Patients With Reduced Ejection Fraction
Authors: Domingo Pascual-Figal, Rolf Wachter, Michele Senni, Weibin Bao, Adele Noè, Heike Schwende, Dmytro Butylin, Margaret F. Prescott, Jacek Gniot, Maria Mozheiko, Malgorzata Lelonek, Antonio Reyes Dominguez, Thomas Horacek, Enrique Garcia del Rio, Zhanna Kobalava, Christian Eugen Mueller, Yuksel Cavusoglu, Ewa Straburzynska-Migaj, Miroslav Slanina, Juergen vom Dahl, Michele Senni, Alisdair Ryding, Andrew Moriarty, Manuel Beltran Robles, Julio Nunez Villota, Antonio Garcia Quintana, Thorsten Nitschke, Jose Manuel Garcia Pinilla, Luis Almenar Bonet, Said Chaaban, Samia Filali zaatari, Jindrich Spinar, Wlodzimierz Musial, Khaled Abdelbaki, Jan Belohlavek, Wolfgang Fehske, Michael Carlos Bott, Geir Hoegalmen, Marisa Crespo Leiro, Ismail Turkay Ozcan, Wilfried Mullens, Radim Kryza, Riadh Al-Ani, Krystyna Loboz-Grudzien, Lyudmila Ermoshkina, Silvia Hojerova, Alberto Alfredo Fernandez, Lenka Spinarova, Harald Lapp, Efraim Bulut, Filipa Almeida, Alexander Vishnevsky, Margita Belicova, Domingo Pascual, Klaus Witte, Kenneth Wong, Walter Droogne, Marc Delforge, Martin Peterka, Hans-Georg Olbrich, Stefano Carugo, Jadwiga Nessler, Thao Huynh McGill, Burkhard Huegl, Ibrahim Akin, Ilidio Moreira, Andrey Baglikov, Jeetendra Thambyrajah, Chris Hayes, Marcelo Raul Barrionuevo, Zerrin Yigit, Hakki Kaya, Zdenek Klimsa, Martin Radvan, Christoph Kadel, Ulf Landmesser, Giuseppe Di Tano, Malgorzata Buksinska Lisik, Candida Fonseca, Luis Oliveira, Irene Marques, Luis Miguel Santos, Egon Lenner, Peter Letavay, Manuel Gomez Bueno, Paula Mota, Aaron Wong, Kristian Bailey, Paul Foley, Eduardo Hasbani, Sean Virani, Tony Abdel Massih, Shukri Al-Saif, Milos Taborsky, Marta Kaislerova, Zuzana Motovska, Aron Ariel Cohen, Damien Logeart, Dierk Endemann, Daniel Ferreira, Dulce Brito, Peter Kycina, Entela Bollano, Enrique Galve Basilio, Lorenzo Facila Rubio, Marcos Garcia Aguado, Lilia Beatriz Schiavi, Daniel Francisco Zivano, Eva Lonn, Ali El Sayed, Anne-Catherine Pouleur, Alex Heyse, Alexandr Schee, Rostislav Polasek, Marek Houra, Christophe Tribouilloy, Marie France Seronde, Michel Galinier, Michel Noutsias, Peter Schwimmbeck, Ingo Voigt, Dirk Westermann, Giovanni Pulignano, Johnny Vegsundvaag, Jose Alexandre Da Silva Antunes, Pedro Monteiro, Jan Stevlik, Eva Goncalvesova, Beata Hulkoova, Antonio Juan Castro Fernandez, Ceri Davies, Iain Squire, Philippe Meyer, Richard Sheppard, Tayfun Sahin, Karel Sochor, Guillaume De Geeter, Rolf Wachter, Alexander Schmeisser, Joachim Weil, Ana Oliveira Soares, Olga Bulashova Vasilevna, Andrey Oshurkov, Shahid Junejo Sunderland, Jason Glover, Tomas Exequiel, Eric Decoulx, Sven Meyer, Thomas Muenzel, Fernando Frioes, Georgy Arbolishvili, Anna Tokarcikova, Patric Karlstrom, Joan Carles Trullas Vila, Gonzalo Pena Perez, Rajiv Sankaranarayanan, Thuraia Nageh, Diego Cristian Alasia, Marwan Refaat, Burcu Demirkan, Jehad Al-Buraiki, Shadi Karabsheh
Journal: JACC Heart Failure (2020)

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. NT-proBNP levels reflect cardiac wall stress and predict event risk in patients with acute decompensated heart failure (ADHF). 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. 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. 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)