Unravelling the interplay between hyperkalaemia, renin–angiotensin–aldosterone inhibitor use and clinical outcomes. Data from 9222 chronic heart failure patients of the ESC-HFA-EORP Heart Failure Long-Term Registry

Patrick Rossignol, Mitja Lainscak, Maria G. Crespo-Leiro, Cécile Laroche, Massimo F. Piepoli, Gerasimos S. Filippatos, Giuseppe M.C. Rosano, Gianluigi Savarese, Stefan D. Anker, Petar M. Seferovic, Frank Ruschitzka, Andrew J.S. Coats, Alexandre Mebazaa, Theresa McDonagh, Ana Sahuquillo, Maria Penco, Aldo P. Maggioni, Lars H. Lund, G. B. Christopher Peter Gale, R. S. Branko BeleslinP. L. Andrzej Budaj, R. O. Ovidiu Chioncel, D. E. Nikolaos Dagres, F. R. Nicolas Danchin, S. E. David Erlinge, G. B. Jonathan Emberson, I. L. Michael Glikson, G. B. Alastair Gray, T. R. Meral Kayikcioglu, I. T. Aldo Maggioni, H. U. Klaudia Vivien Nagy, R. U. Aleksandr Nedoshivin, I. T. Anna-Sonia Petronio, N. L. Jolien Roos-Hesselink, S. E. Lars Wallentin, D. E. Uwe Zeymer, A. Mebazaa, A. Coats, R. Ferrari, A. Goda, M. Diez, A. Fernandez, F. Fruhwald, E. Fazlibegovic, P. Gatzov, A. Kurlianskaya, R. Hullin, T. Christodoulides, J. Hradec, O. Wendelboe Nielsen, R. Nedjar, T. Uuetoa, M. Hassanein, J. F.Delgado Jimenez, V. P. Harjola, D. Logeart, V. Chumburidze, D. Tousoulis, D. Milicic, Béla Merkely, E. O'Donoghue, O. Amir, A. Shotan, D. Shafie, M. Metra, A. Matsumori, E. Mirrakhimov, A. Kavoliuniene, A. Erglis, E. Vataman, M. Otljanska, E. Srbinovska Kostovska, D. Cassar DeMarco, J. Drozdz, C. Fonseca, O. Chioncel, M. Dekleva, E. Shkolnik, U. Dahlstrom, M. Lainscak, E. Goncalvesova, A. Temizhan, V. Estrago, G. Bajraktari, J. Auer, K. Ablasser, F. Fruhwald, T. Dolze, K. Brandner, S. Gstrein, G. Poelzl, D. Moertl, S. Reiter, A. Podczeck-Schweighofer, A. Muslibegovic, M. Vasilj, E. Fazlibegovic, M. Cesko, D. Zelenika, B. Palic, D. Pravdic, D. Cuk, K. Vitlianova, T. Katova, T. Velikov, T. Kurteva, P. Gatzov, D. Kamenova, M. Antova, V. Sirakova, J. Krejci, M. Mikolaskova, J. Spinar, J. Krupicka, F. Malek, M. Hegarova, M. Lazarova, Z. Monhart, M. Hassanein, M. Sobhy, F. El Messiry, A. H. El Shazly, Y. Elrakshy, A. Youssef, A. A. Moneim, M. Noamany, A. Reda, T. K.Abdel Dayem, N. Farag, S. Ibrahim Halawa, M. Abdel Hamid, K. Said, A. Saleh, H. Ebeid, R. Hanna, R. Aziz, O. Louis, M. A. Enen, B. S. Ibrahim, G. Nasr, A. Elbahry, H. Sobhy, M. Ashmawy, M. Gouda, W. Aboleineen, Y. Bernard, P. Luporsi, N. Meneveau, M. Pillot, M. Morel, M. F. Seronde, F. Schiele, F. Briand, F. Delahaye, T. Damy, J. C. Eicher, P. de Groote, M. Fertin, N. Lamblin, R. Isnard, C. Lefol, S. Thevenin, A. Hagege, G. Jondeau, D. Logeart, V. Le Marcis, J. F. Ly, D. Coisne, B. Lequeux, V. Le Moal, S. Mascle, P. Lotton, N. Behar, E. Donal, C. Thebault, C. Ridard, A. Reynaud, A. Basquin, F. Bauer, R. Codjia, M. Galinier, P. Tourikis, M. Stavroula, D. Tousoulis, C. Stefanadis, C. Chrysohoou, I. Kotrogiannis, V. Matzaraki, T. Dimitroula, A. Karavidas, G. Tsitsinakis, C. Kapelios, J. Nanas, H. Kampouri, E. Nana, E. Kaldara, A. Eugenidou, P. Vardas, I. Saloustros, A. Patrianakos, T. Tsaknakis, S. Evangelou, N. Nikoloulis, H. Tziourganou, A. Tsaroucha, A. Papadopoulou, A. Douras, L. Polgar, A. Kosztin, N. Nyolczas, A. Csaba Nagy, R. Halmosi, J. Elber, I. Alony, A. Shotan, A. Vazan Fuhrmann, O. Amir, S. Romano, S. Marcon, M. Penco, M. Di Mauro, E. Lemme, V. Carubelli, R. Rovetta, M. Bulgari, F. Quinzani, C. Lombardi, S. Bosi, G. Schiavina, A. Squeri, A. Barbieri, G. Di Tano, S. Pirelli, A. Fucili, T. Passero, S. Musio, M. Di Biase, M. Correale, G. Salvemini, S. Brognoli, E. Zanelli, A. Giordano, P. Agostoni, G. Italiano, E. Salvioni, S. Copelli, M. G. Modena, L. Reggianini, C. Valenti, A. Olaru, S. Bandino, M. Deidda, G. Mercuro, C. Cadeddu Dessalvi, P. N. Marino, M. V. Di Ruocco, C. Sartori, C. Piccinino, G. Parrinello, G. Licata, D. Torres, S. Giambanco, S. Busalacchi, S. Arrotti, S. Novo, R. M. Inciardi, P. Pieri, P. R. Chirco, M. Ausilia Galifi, G. Teresi, D. Buccheri, A. Minacapelli, M. Veniani, A. Frisinghelli, S. G. Priori, S. Cattaneo, C. Opasich, A. Gualco, M. Pagliaro, M. Mancone, F. Fedele, A. Cinque, M. Vellini, I. Scarfo, F. Romeo, F. Ferraiuolo, D. Sergi, M. Anselmi, F. Melandri, E. Leci, E. Iori, V. Bovolo, S. Pidello, S. Frea, S. Bergerone, M. Botta, F. G. Canavosio, F. Gaita, M. Merlo, M. Cinquetti, G. Sinagra, F. Ramani, E. Fabris, D. Stolfo, J. Artico, D. Miani, C. Fresco, C. Daneluzzi, A. Proclemer, M. Cicoira, L. Zanolla, G. Marchese, F. Torelli, C. Vassanelli, N. Voronina, V. Tamakauskas, V. Smalinskas, R. Karaliute, I. Petraskiene, E. Kazakauskaite, E. Rumbinaite, A. Kavoliuniene, V. Vysniauskas, R. Brazyte-Ramanauskiene, D. Petraskiene, S. Stankala, P. Switala, Z. Juszczyk, W. Sinkiewicz, W. Gilewski, J. Pietrzak, T. Orzel, P. Kasztelowicz, P. Kardaszewicz, M. Lazorko-Piega, J. Gabryel, K. Mosakowska, J. Bellwon, A. Rynkiewicz, G. Raczak, E. Lewicka, A. Dabrowska-Kugacka, R. Bartkowiak, B. Sosnowska-Pasiarska, B. Wozakowska-Kaplon, A. Krzeminski, M. Zabojszcz, E. Mirek-Bryniarska, A. Grzegorzko, K. Bury, J. Nessler, J. Zalewski, A. Furman, M. Broncel, A. Poliwczak, A. Bala, P. Zycinski, M. Rudzinska, L. Jankowski, J. D. Kasprzak, L. Michalak, K. Wojtczak Soska, J. Drozdz, I. Huziuk, A. Retwinski, P. Flis, J. Weglarz, A. Bodys, S. Grajek, M. Kaluzna-Oleksy, E. Straburzynska-Migaj, R. Dankowski, K. Szymanowska, J. Grabia, A. Szyszka, A. Nowicka, M. Samcik, L. Wolniewicz, K. Baczynska, K. Komorowska, I. Poprawa, E. Komorowska, D. Sajnaga, A. Zolbach, A. Dudzik-Plocica, A. F. Abdulkarim, A. Lauko-Rachocka, L. Kaminski, A. Kostka, A. Cichy, P. Ruszkowski, M. Splawski, G. Fitas, A. Szymczyk, A. Serwicka, A. Fiega, D. Zysko, W. Krysiak, S. Szabowski, E. Skorek, P. Pruszczyk, P. Bienias, M. Ciurzynski, M. Welnicki, A. Mamcarz, A. Folga, T. Zielinski, T. Rywik, P. Leszek, M. Sobieszczanska-Malek, M. Piotrowska, K. Kozar-Kaminska, K. Komuda, J. Wisniewska, A. Tarnowska, P. Balsam, M. Marchel, G. Opolski, A. Kaplon-Cieslicka, R. J. Gil, O. Mozenska, K. Byczkowska, K. Gil, A. Pawlak, A. Michalek, P. Krzesinski, K. Piotrowicz, B. Uzieblo-Zyczkowska, A. Stanczyk, A. Skrobowski, P. Ponikowski, E. Jankowska, P. Rozentryt, L. Polonski, E. Gadula-Gacek, E. Nowalany-Kozielska, A. Kuczaj, Z. Kalarus, M. Szulik, K. Przybylska, J. Klys, G. Prokop-Lewicka, A. Kleinrok, C. Tavares Aguiar, A. Ventosa, S. Pereira, R. Faria, J. Chin, I. De Jesus, R. Santos, P. Silva, N. Moreno, C. Queirós, C. Lourenço, A. Pereira, A. Castro, A. Andrade, T. Oliveira Guimaraes, S. Martins, R. Placido, G. Lima, D. Brito, A. R. Francisco, R. Cardiga, M. Proenca, I. Araujo, F. Marques, B. Moura, S. Leite, M. Campelo, J. Silva-Cardoso, J. Rodrigues, I. Rangel, E. Martins, A. Sofia Correia, M. Peres, L. Marta, G. Ferreira da Silva, D. Severino, D. Durao, S. Leao, P. Magalhaes, I. Moreira, A. Filipa Cordeiro, C. Ferreira, C. Araujo, A. Ferreira, A. Baptista, M. Radoi, G. Bicescu, D. Vinereanu, C. J. Sinescu, C. Macarie, R. Popescu, I. Daha, G. A. Dan, C. Stanescu, A. Dan, E. Craiu, E. Nechita, V. Aursulesei, R. Christodorescu, P. Otasevic, P. M. Seferovic, D. Simeunovic, A. D. Ristic, V. Celic, M. Pavlovic-Kleut, J. Suzic Lazic, B. Stojcevski, B. Pencic, A. Stevanovic, A. Andric, Dragan Simić, Milika Ašanin, V. Iric-Cupic, M. Jovic, G. Davidovic, S. Milanov, V. Mitic, V. Atanaskovic, S. Antic, M. Pavlovic, D. Stanojevic, V. Stoickov, S. Ilic, M. Deljanin Ilic, D. Petrovic, S. Stojsic, S. Kecojevic, S. Dodic, N. Cemerlic Adic, M. Cankovic, J. Stojiljkovic, B. Mihajlovic, A. Radin, S. Radovanovic, M. Krotin, A. Klabnik, E. Goncalvesova, M. Pernicky, J. Murin, F. Kovar, J. Kmec, H. Semjanova, M. Strasek, M. Savnik Iskra, T. Ravnikar, N. Cernic Suligoj, J. Komel, Z. Fras, B. Jug, T. Glavic, R. Losic, M. Bombek, I. Krajnc, B. Krunic, S. Horvat, D. Kovac, D. Rajtman, V. Cencic, M. Letonja, R. Winkler, M. Valentincic, C. Melihen-Bartolic, A. Bartolic, M. Pusnik Vrckovnik, M. Kladnik, C. Slemenik Pusnik, A. Marolt, J. Klen, B. Drnovsek, B. Leskovar, M. J.Fernandez Anguita, J. C.Gallego Page, F. M.Salmeron Martinez, J. Andres, A. Bayes-Genis, S. Mirabet, A. Mendez, L. Garcia-Cosio, E. Roig, V. Leon, J. Gonzalez-Costello, G. Muntane, A. Garay, V. Alcade-Martinez, S. Lopez Fernandez, R. Rivera-Lopez, M. Puga-Martinez, M. Fernandez-Alvarez, J. L. Serrano-Martinez, Z. Grille-Cancela, R. Marzoa-Rivas, P. Blanco-Canosa, M. J. Paniagua-Martin, E. Barge-Caballero, I. Laynez Cerdena, I. Famara Hernandez Baldomero, A. Lara Padron, S. Ofelia Rosillo, R. Dalmau Gonzalez-Gallarza, O. Salvador Montanes, A. M.Iniesta Manjavacas, A. Castro Conde, A. Araujo, T. Soria, P. Garcia-Pavia, M. Gomez-Bueno, M. Cobo-Marcos, L. Alonso-Pulpon, J. Segovia Cubero, I. Sayago, A. Gonzalez-Segovia, A. Briceno, P. Escribano Subias, M. Vicente Hernandez, M. J.Ruiz Cano, M. A.Gomez Sanchez, J. F.Delgado Jimenez, E. Barrios Garrido-Lestache, J. M.Garcia Pinilla, B. Garcia de la Villa, A. Sahuquillo, R. Bravo Marques, F. Torres Calvo, M. T. Perez-Martinez, M. R. Gracia-Rodenas, I. P. Garrido-Bravo, F. Pastor-Perez, D. A. Pascual-Figal, B. Diaz Molina, J. Orus, F. Epelde Gonzalo, V. Bertomeu, R. Valero, R. Martinez-Abellan, J. Quiles, J. A. Rodrigez-Ortega, I. Mateo, A. ElAmrani, C. Fernandez-Vivancos, D. Bierge Valero, L. Almenar-Bonet, I. J. Sanchez-Lazaro, E. Marques-Sule, L. Facila-Rubio, J. Perez-Silvestre, P. Garcia-Gonzalez, F. Ridocci-Soriano, D. Garcia-Escriva, A. Pellicer-Cabo, L. de la Fuente Galan, J. Lopez Diaz, A. Recio Platero, J. C. Arias, T. Blasco-Peiro, M. Sanz Julve, E. Sanchez-Insa, C. Aured-Guallar, A. Portoles-Ocampo, M. Melin, E. Hägglund, A. Stenberg, I. M. Lindahl, B. Asserlund, L. Olsson, U. Dahlström, M. Afzelius, P. Karlström, L. Tengvall, B. Olsson, S. Kalayci, A. Temizhan, Y. Cavusoglu, E. Gencer, M. B. Yilmaz, H. Gunes

Research output: Contribution to journalArticlepeer-review

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Abstract

Aims: We assessed the interplay between hyperkalaemia (HK) and renin–angiotensin–aldosterone system inhibitor (RAASi) use, dose and discontinuation, and their association with all-cause or cardiovascular death in patients with chronic heart failure (HF). We hypothesized that HK-associated increased death may be related to RAASi withdrawal. Methods and results: The ESC-HFA-EORP Heart Failure Long-Term Registry was used. Among 9222 outpatients (HF with reduced ejection fraction: 60.6%, HF with mid-range ejection fraction: 22.9%, HF with preserved ejection fraction: 16.5%) from 31 countries, 16.6% had HK (≥5.0 mmol/L) at baseline. Angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) was used in 88.3%, a mineralocorticoid receptor antagonist (MRA) in 58.7%, or a combination in 53.2%; of these, at ≥50% of target dose in ACEi: 61.8%; ARB: 64.7%; and MRA: 90.3%. At a median follow-up of 12.2 months, there were 789 deaths (8.6%). Both hypokalaemia and HK were independently. associated with higher mortality, and ACEi/ARB prescription at baseline with lower mortality. MRA prescription was not retained in the model. In multivariable analyses, HK at baseline was independently associated with MRA non-prescription at baseline and subsequent discontinuation. When considering subsequent discontinuation of RAASi (instead of baseline use), HK was no longer found associated with all-cause deaths. Importantly, all RAASi (ACEi, ARB, or MRA) discontinuations were strongly associated with mortality. Conclusions: In HF, hyper- and hypokalaemia were associated with mortality. However, when adjusting for RAASi discontinuation, HK was no longer associated with mortality, suggesting that HK may be a risk marker for RAASi discontinuation rather than a risk factor for worse outcomes.

Original languageEnglish
Pages (from-to)1378-1389
Number of pages12
JournalEuropean Journal of Heart Failure
Volume22
Issue number8
DOIs
Publication statusPublished - 1 Aug 2020

Keywords

  • Heart failure
  • Hyperkalaemia
  • Hypokalaemia
  • Mineralocorticoid receptor antagonists
  • Prognosis
  • Renin–angiotensin–aldosterone system inhibitors

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