Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial
Maggioni, Aldo P. ; Greene, Stephen J. ; Fonarow, Gregg C. ; Böhm, Michael ; Zannad, Faiez ; Solomon, Scott D. ; Lewis, Eldrin F. ; Baschiera, Fabio ; Hua, Tsushung A. ; Gimpelewicz, Claudio R. ; Lesogor, Anastasia ; Gheorghiade, Mihai ; Ramos, Silvina ; Luna, Alejandra ; Miriuka, Santiago ; Diez, Mirta ; Perna, Eduardo ; Luquez, Hugo ; Pinna, Jorge Garcia ; Castagnino, Jorge ; Alvarenga, Pablo ; Ibañez, Julio ; Blumberg, Eduardo Salmon ; Dizeo, Claudio ; Guerrero, Rodolfo Ahuad ; Schygiel, Pablo ; Milesi, Rodolfo ; Sosa, Carlos ; Hominal, Miguel ; Marquez, Lilia Lobo ; Poy, Carlos ; Hasbani, Eduardo ; Vico, Marisa ; Fernandez, Alberto ; Vita, Nestor ; Vanhaecke, Johan ; De Keulenaer, Gilles ; Striekwold, Harry ; Vervoort, Geert ; Vrolix, Mathias ; Henry, Philippe ; Dendale, Paul ; Smolders, Walter ; Marechal, Patrick ; Vandekerckhove, Hans ; Oliveira, Mucio ; Neuenschwande, Fernando ; Reis, Gilmar ; Saraiva, Jose ; Bodanese, Luiz ; Canesin, Manoel ; Greco, Oswaldo ; Bassan, Roberto ; Marino, Roberto Luis ; Giannetti, Nadia ; Moe, Gordon ; Sussex, Bruce ; Sheppard, Richard ; Huynh, Thao ; Stewart, Robert ; Haddad, Haissam ; Echeverria, Luis ; Quintero, Adalberto ; Torres, Adriana ; Jaramillo, Mónica ; Lopez, Mónica ; Mendoza, Fernan ; Florez, Noel ; Cotes, Carlos ; Garcia, Magali ; Belohlavek, Jan ; Hradec, Jaromir ; Peterka, Martin ; Gregor, Pavel ; Monhart, Zdenek ; Jansky, Petr ; Kettner, Jiri ; Reichert, Petr ; Spinar, Jindrich ; Brabec, Tomas ; Hutyra, Martin ; Solar, Miroslav ; Pietilä, Mikko ; Nyman, Kai ; Pajari, Risto ; Cohen, Ariel ; Galinier, Michel ; Gosse, Philippe ; Livarek, Bernard ; Neuder, Yannick ; Jourdain, Patrick ; Picard, François ; Isnard, Richard ; Hoppe, Uta ; Kaeaeb, Stefan ; Rosocha, Stefan ; Prondzinsky, Roland ; Felix, Stephan ; Duengen, Hans-Dirk ; Figulla, Hans-Reiner ; Fischer, Sven ; Behrens, Steffen ; Stawowy, Philipp ; Kruells-Muench, Juergen ; Knebel, Fabian ; Nienaber, Christoph ; Werner, Dierk ; Aron, Wilma ; Remppis, Bjoern ; Hambrecht, Rainer ; Kisters, Klaus ; Werner, Nikos ; Hoffmann, Stefan ; Rossol, Siegbert ; Geiss, Ernst ; Graf, Kristof ; Hamann, Frank ; von Scheidt, Wolfgang ; Schwinger, Robert ; Tebbe, Ulrich ; Costard-Jaeckle, Angelika ; Lueders, Stephan ; Heitzer, Thomas ; Leutermann-Oei, Marie-Louise ; Braun-Dullaeus, Ruediger ; Roehnisch, Jens-Uwe ; Muth, Gerhard ; Goette, Andreas ; Rotter, Achim ; Ebelt, Henning ; Olbrich, Hans-Georg ; Mitrovic, Veselin ; Hengstenberg, Christian ; Schellong, Sebastian ; Zamolyi, Karoly ; Vertes, Andras ; Matoltsy, Andras ; Palinkas, Attila ; Herczeg, Bela ; Apro, Dezso ; Lupkovics, Geza ; Tomcsanyi, Janos ; Toth, Kalman ; Mathur, Atul ; Banker, Darshan ; Bharani, Anil ; Arneja, Jaspal ; Khan, Aziz ; Gadkari, Milind ; Hiremath, Jagdish ; Patki, Nitin ; Kumbla, Makund ; Santosh, M.J. ; Ravikishore, A.G. ; Abhaichand, Rajpal ; Maniyal, Vijayakukmar ; Nanjappa, Manjunath ; Reddy, P. Naveen ; Chockalingam, Kulasekaran ; Premchand, Rajendra ; Mahajan, Vijay ; Lewis, Basil ; Wexler, Dov ; Shochat, Michael ; Keren, Andre ; Omary, Muhamad ; Katz, Amos ; Marmor, Alon ; Lembo, Giuseppe ; Di Somma, Salvatore ; Boccanelli, Alessandro ; Barbiero, Mario ; Pajes, Giuseppe ; De Servi, Stefano ; Greco, Dott Cosimo ; De Santis, Fernando ; Floresta, Agata ; Visconti, Luigi Oltrona ; Piovaccari, Giancarlo ; Cavallini, Claudio ; Di Biase, Matteo ; Masini, Dott Franco ; Vassanelli, Corrado ; Viecca, Maurizio ; Cangemi, Dott Francesco ; Pirelli, Salvatore ; Borghi, Claudio ; Volpe, Massimo ; Branzi, Angelo ; Percoco, Dott Giovanni ; Severi, Silvia ; Santini, Alberto ; De Lorenzi, Ettore ; Metra, Marco ; Zacà, Valerio ; Mortara, Andrea ; Tranquilino, Francisco P. ; Babilonia, Noe A. ; Ferrolino, Arthur M. ; Manlutac, Benjamin ; Dluzniewski, Miroslaw ; Dzielinska, Zofia ; Nowalany-Kozie, Ewa ; Mazurek, Walentyna ; Wierzchowiecki, Jerzy ; Wysokinski, Andrzej ; Szachniewicz, Joanna ; Romanowski, Witold ; Krauze-Wielicka, Magdalena ; Jankowski, Piotr ; Berkowski, Piotr ; Szelemej, Roman ; Kleinrok, Andrzej ; Kornacewicz-Jac, Zdzislawa ; Vintila, Marius ; Vladoianu, Mircea ; Militaru, Constantin ; Dan, Gheorghe ; Dorobantu, Maria ; Dragulescu, Stefan ; Kostenko, Victor ; Vishnevsky, Alexandr ; Goloschekin, Boris ; Tyrenko, Vadim ; Gordienko, Alexander ; Kislyak, Oxana ; Martsevich, Sergey ; Kuchmin, Alexey ; Karpov, Yurii ; Fomin, Igor ; Shvarts, Yury ; Orlikova, Olga ; Ershova, Olga ; Berkovich, Olga ; Sitnikova, Maria ; Pakhomova, Inna ; Boldueva, Svetlana ; Tyurina, Tatiana ; Simanenkov, Vladimir ; Boyarkin, Mikhail ; Novikova, Nina ; Tereschenko, Sergey ; Zadionchenko, Vladimir ; Shogenov, Zaur ; Gordeev, Ivan ; Moiseev, Valentin ; Wong, Raymond ; Ong, Hean Yee ; Le Tan, Ju ; Goncalvesova, Eva ; Kovar, Frantisek ; Skalina, Ivan ; Kasperova, Viera ; Hojerova, Silvia ; Szentivanyi, Miroslav ; Stancak, Branislav ; Babcak, Marian ; Kycina, Peter ; Poliacik, Pavol ; Toth, Peter ; Sirotiakova, Jana ; de Sa, Esteban Lopez ; Bueno, Manuel Gomez ; Selles, Manuel Martinez ; Cabrera, Jose Angel ; Freire, Ramon Bover ; Gonzalez Juanatey, Jose Ramon ; Comin, Josep ; Soriano, FranciscoRidocci ; Lopez, Alejandro ; Vicho, Raul ; Lama, Manuel Geraldia ; Schaufelberger, Maria ; Brunotte, Richard ; Ullman, Bengt ; Hagerman, Inger ; Cizinsky, Stella ; Cherng, Wen-Jin ; Yu, Wen-Chung ; Kuo, Chi-Tai ; Chang, Kuan-Cheng ; Lai, Wen-Ter ; Kuo, Jen-Yuan ; Ural, Dilek ; Badak, Ozer ; Akin, Mustafa ; Yigit, Zerrin ; Yokusoglu, Mehmet ; Yilmaz, Mehmet ; Abaci, Adnan ; Ebinc, Haksun ; Perlman, Richard ; Parish, David ; Bergin, James ; Burnham, Kenneth ; Brown, Christopher ; Lundbye, Justin ; Williams, Celeste ; Eisen, Howard ; Juneman, Elizabeth ; Joseph, Susan ; Peberdy, Mary Ann ; Peura, Jennifer ; Gupta, Vishal ; Habet, Kalim ; French, William ; Mody, Freny ; Graham, Susan ; Hazelrigg, Monica ; Chung, Eugene ; Dunlap, Stephanie ; Nikolaidis, Lazaros ; Najjar, Samer ; Katz, Richard ; Murali, Srinivas ; Izzo, Joseph L. ; Callister, Tracy ; Phillips, Roland ; Lippolis, Nicholas ; Winterton, John ; Meymandi, Sheba ; Heilman, Karl ; Oren, Ron ; Zolty, Ronald ; Brottman, Michael ; Gunawardena, D.R. ; Adams, Kirkwood ; Barnard, Denise ; Klapholz, Marc ; Fulmer, James ; Ramos, Silvina ; Luna, Alejandra ; Miriuka, Santiago ; Diez, Mirta ; Perna, Eduardo ; Luquez, Hugo ; Pinna, Jorge Garcia ; Castagnino, Jorge ; Alvarenga, Pablo ; Ibañez, Julio ; Blumberg, Eduardo Salmon ; Dizeo, Claudio ; Guerrero, Rodolfo Ahuad ; Schygiel, Pablo ; Milesi, Rodolfo ; Sosa, Carlos ; Hominal, Miguel ; Marquez, Lilia Lobo ; Poy, Carlos ; Hasbani, Eduardo ; Vico, Marisa ; Fernandez, Alberto ; Vita, Nestor ; Vanhaecke, Johan ; De Keulenaer, Gilles ; Striekwold, Harry ; Vervoort, Geert ; Vrolix, Mathias ; Henry, Philippe ; Dendale, Paul ; Smolders, Walter ; Marechal, Patrick ; Vandekerckhove, Hans ; Oliveira, Mucio ; Neuenschwande, Fernando ; Reis, Gilmar ; Saraiva, Jose ; Bodanese, Luiz ; Canesin, Manoel ; Greco, Oswaldo ; Bassan, Roberto ; Marino, Roberto Luis ; Giannetti, Nadia ; Moe, Gordon ; Sussex, Bruce ; Sheppard, Richard ; Huynh, Thao ; Stewart, Robert ; Haddad, Haissam ; Echeverria, Luis ; Quintero, Adalberto ; Torres, Adriana ; Jaramillo, Mónica ; Lopez, Mónica ; Mendoza, Fernan ; Florez, Noel ; Cotes, Carlos ; Garcia, Magali ; Belohlavek, Jan ; Hradec, Jaromir ; Peterka, Martin ; Gregor, Pavel ; Monhart, Zdenek ; Jansky, Petr ; Kettner, Jiri ; Reichert, Petr ; Spinar, Jindrich ; Brabec, Tomas ; Hutyra, Martin ; Solar, Miroslav ; Pietilä, Mikko ; Nyman, Kai ; Pajari, Risto ; Cohen, Ariel ; Galinier, Michel ; Gosse, Philippe ; Livarek, Bernard ; Neuder, Yannick ; Jourdain, Patrick ; Picard, François ; Isnard, Richard ; Hoppe, Uta ; Kaeaeb, Stefan ; Rosocha, Stefan ; Prondzinsky, Roland ; Felix, Stephan ; Duengen, Hans-Dirk ; Figulla, Hans-Reiner ; Fischer, Sven ; Behrens, Steffen ; Stawowy, Philipp ; Kruells-Muench, Juergen ; Knebel, Fabian ; Nienaber, Christoph ; Werner, Dierk ; Aron, Wilma ; Remppis, Bjoern ; Hambrecht, Rainer ; Kisters, Klaus ; Werner, Nikos ; Hoffmann, Stefan ; Rossol, Siegbert ; Geiss, Ernst ; Graf, Kristof ; Hamann, Frank ; von Scheidt, Wolfgang ; Schwinger, Robert ; Tebbe, Ulrich ; Costard-Jaeckle, Angelika ; Lueders, Stephan ; Heitzer, Thomas ; Leutermann-Oei, Marie-Louise ; Braun-Dullaeus, Ruediger ; Roehnisch, Jens-Uwe ; Muth, Gerhard ; Goette, Andreas ; Rotter, Achim ; Ebelt, Henning ; Olbrich, Hans-Georg ; Mitrovic, Veselin ; Hengstenberg, Christian ; Schellong, Sebastian ; Zamolyi, Karoly ; Vertes, Andras ; Matoltsy, Andras ; Palinkas, Attila ; Herczeg, Bela ; Apro, Dezso ; Lupkovics, Geza ; Tomcsanyi, Janos ; Toth, Kalman ; Mathur, Atul ; Banker, Darshan ; Bharani, Anil ; Arneja, Jaspal ; Khan, Aziz ; Gadkari, Milind ; Hiremath, Jagdish ; Patki, Nitin ; Kumbla, Makund ; Santosh, M.J. ; Ravikishore, A.G. ; Abhaichand, Rajpal ; Maniyal, Vijayakukmar ; Nanjappa, Manjunath ; Reddy, P. Naveen ; Chockalingam, Kulasekaran ; Premchand, Rajendra ; Mahajan, Vijay ; Lewis, Basil ; Wexler, Dov ; Shochat, Michael ; Keren, Andre ; Omary, Muhamad ; Katz, Amos ; Marmor, Alon ; Lembo, Giuseppe ; Di Somma, Salvatore ; Boccanelli, Alessandro ; Barbiero, Mario ; Pajes, Giuseppe ; De Servi, Stefano ; Greco, Dott Cosimo ; De Santis, Fernando ; Floresta, Agata ; Visconti, Luigi Oltrona ; Piovaccari, Giancarlo ; Cavallini, Claudio ; Di Biase, Matteo ; Masini, Dott Franco ; Vassanelli, Corrado ; Viecca, Maurizio ; Cangemi, Dott Francesco ; Pirelli, Salvatore ; Borghi, Claudio ; Volpe, Massimo ; Branzi, Angelo ; Percoco, Dott Giovanni ; Severi, Silvia ; Santini, Alberto ; De Lorenzi, Ettore ; Metra, Marco ; Zacà, Valerio ; Mortara, Andrea ; Tranquilino, Francisco P. ; Babilonia, Noe A. ; Ferrolino, Arthur M. ; Manlutac, Benjamin ; Dluzniewski, Miroslaw ; Dzielinska, Zofia ; Nowalany-Kozie, Ewa ; Mazurek, Walentyna ; Wierzchowiecki, Jerzy ; Wysokinski, Andrzej ; Szachniewicz, Joanna ; Romanowski, Witold ; Krauze-Wielicka, Magdalena ; Jankowski, Piotr ; Berkowski, Piotr ; Szelemej, Roman ; Kleinrok, Andrzej ; Kornacewicz-Jac, Zdzislawa ; Vintila, Marius ; Vladoianu, Mircea ; Militaru, Constantin ; Dan, Gheorghe ; Dorobantu, Maria ; Dragulescu, Stefan ; Kostenko, Victor ; Vishnevsky, Alexandr ; Goloschekin, Boris ; Tyrenko, Vadim ; Gordienko, Alexander ; Kislyak, Oxana ; Martsevich, Sergey ; Kuchmin, Alexey ; Karpov, Yurii ; Fomin, Igor ; Shvarts, Yury ; Orlikova, Olga ; Ershova, Olga ; Berkovich, Olga ; Sitnikova, Maria ; Pakhomova, Inna ; Boldueva, Svetlana ; Tyurina, Tatiana ; Simanenkov, Vladimir ; Boyarkin, Mikhail ; Novikova, Nina ; Tereschenko, Sergey ; Zadionchenko, Vladimir ; Shogenov, Zaur ; Gordeev, Ivan ; Moiseev, Valentin ; Wong, Raymond ; Ong, Hean Yee ; Le Tan, Ju ; Goncalvesova, Eva ; Kovar, Frantisek ; Skalina, Ivan ; Kasperova, Viera ; Hojerova, Silvia ; Szentivanyi, Miroslav ; Stancak, Branislav ; Babcak, Marian ; Kycina, Peter ; Poliacik, Pavol ; Toth, Peter ; Sirotiakova, Jana ; de Sa, Esteban Lopez ; Bueno, Manuel Gomez ; Selles, Manuel Martinez ; Cabrera, Jose Angel ; Freire, Ramon Bover ; Gonzalez Juanatey, Jose Ramon ; Comin, Josep ; Soriano, FranciscoRidocci ; Lopez, Alejandro ; Vicho, Raul ; Lama, Manuel Geraldia ; Schaufelberger, Maria ; Brunotte, Richard ; Ullman, Bengt ; Hagerman, Inger ; Cizinsky, Stella ; Cherng, Wen-Jin ; Yu, Wen-Chung ; Kuo, Chi-Tai ; Chang, Kuan-Cheng ; Lai, Wen-Ter ; Kuo, Jen-Yuan ; Ural, Dilek ; Badak, Ozer ; Akin, Mustafa ; Yigit, Zerrin ; Yokusoglu, Mehmet ; Yilmaz, Mehmet ; Abaci, Adnan ; Ebinc, Haksun ; Perlman, Richard ; Parish, David ; Bergin, James ; Burnham, Kenneth ; Brown, Christopher ; Lundbye, Justin ; Williams, Celeste ; Eisen, Howard ; Juneman, Elizabeth ; Joseph, Susan ; Peberdy, Mary Ann ; Peura, Jennifer ; Gupta, Vishal ; Habet, Kalim ; French, William ; Mody, Freny ; Graham, Susan ; Hazelrigg, Monica ; Chung, Eugene ; Dunlap, Stephanie ; Nikolaidis, Lazaros ; Najjar, Samer ; Katz, Richard ; Murali, Srinivas ; Izzo, Joseph L. ; Callister, Tracy ; Phillips, Roland ; Lippolis, Nicholas ; Winterton, John ; Meymandi, Sheba ; Heilman, Karl ; Oren, Ron ; Zolty, Ronald ; Brottman, Michael ; Gunawardena, D.R. ; Adams, Kirkwood ; Barnard, Denise ; Klapholz, Marc ; Fulmer, James
In: European Heart Journal, 2013, vol. 34, no. 40, p. 3117-3127
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- Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without DM