@article{3104135,
    title = "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",
    author = "Rossignol, P. and Lainscak, M. and Crespo-Leiro, M.G. and Laroche, C. and Piepoli, M.F. and Filippatos, G. and Rosano, G.M.C. and Savarese, G. and Anker, S.D. and Seferovic, P.M. and Ruschitzka, F. and Coats, A.J.S. and Mebazaa, A. and McDonagh, T. and Sahuquillo, A. and Penco, M. and Maggioni, A.P. and Lund, L.H. and Christopher Peter Gale, G.B. and Branko Beleslin, R.S. and Andrzej Budaj, P.L. and Ovidiu Chioncel, R.O. and Nikolaos Dagres, D.E. and Nicolas Danchin, F.R. and David Erlinge, S.E. and Jonathan Emberson, G.B. and Michael Glikson, I.L. and Alastair Gray, G.B. and Meral Kayikcioglu, T.R. and Aldo Maggioni, I.T. and Klaudia Vivien Nagy, H.U. and Aleksandr Nedoshivin, R.U. and Anna-Sonia Petronio, I.T. and Jolien Roos-Hesselink, N.L. and Lars Wallentin, S.E. and Uwe Zeymer, D.E. and Anker, S. and Mebazaa, A. and Coats, A. and Filippatos, G. and Ferrari, R. and Maggioni, A.P. and Goda, A. and Diez, M. and Fernandez, A. and Fruhwald, F. and Fazlibegovic, E. and Gatzov, P. and Kurlianskaya, A. and Hullin, R. and Christodoulides, T. and Hradec, J. and Nielsen, O.W. and Nedjar, R. and Uuetoa, T. and Hassanein, M. and Jimenez, J.F.D. and Harjola, V.P. and Logeart, D. and Chumburidze, V. and Tousoulis, D. and Milicic, D. and Merkely, B. and O'Donoghue, E. and Amir, O. and Shotan, A. and Shafie, D. and Metra, M. and Matsumori, A. and Mirrakhimov, E. and Kavoliuniene, A. and Erglis, A. and Vataman, E. and Otljanska, M. and Kostovska, E.S. and DeMarco, D.C. and Drozdz, J. and Fonseca, C. and Chioncel, O. and Dekleva, M. and Shkolnik, E. and Dahlstrom, U. and Lainscak, M. and Goncalvesova, E. and Temizhan, A. and Estrago, V. and Bajraktari, G. and Auer, J. and Ablasser, K. and Fruhwald, F. and Dolze, T. and Brandner, K. and Gstrein, S. and Poelzl, G. and Moertl, D. and Reiter, S. and Podczeck-Schweighofer, A. and Muslibegovic, A. and Vasilj, M. and Fazlibegovic, E. and Cesko, M. and Zelenika, D. and Palic, B. and Pravdic, D. and Cuk, D. and Vitlianova, K. and Katova, T. and Velikov, T. and Kurteva, T. and Gatzov, P. and Kamenova, D. and Antova, M. and Sirakova, V. and Krejci, J. and Mikolaskova, M. and Spinar, J. and Krupicka, J. and Malek, F. and Hegarova, M. and Lazarova, M. and Monhart, Z. and Hassanein, M. and Sobhy, M. and El Messiry, F. and El Shazly, A.H. and Elrakshy, Y. and Youssef, A. and Moneim, A.A. and Noamany, M. and Reda, A. and Dayem, T.K.A. and Farag, N. and Halawa, S.I. and Hamid, M.A. and Said, K. and Saleh, A. and Ebeid, H. and Hanna, R. and Aziz, R. and Louis, O. and Enen, M.A. and Ibrahim, B.S. and Nasr, G. and Elbahry, A. and Sobhy, H. and Ashmawy, M. and Gouda, M. and Aboleineen, W. and Bernard, Y. and Luporsi, P. and Meneveau, N. and Pillot, M. and Morel, M. and Seronde, M.-F. and Schiele, F. and Briand, F. and Delahaye, F. and Damy, T. and Eicher, J.-C. and de Groote, P. and Fertin, M. and Lamblin, N. and Isnard, R. and Lefol, C. and Thevenin, S. and Hagege, A. and Jondeau, G. and Logeart, D. and Le Marcis, V. and Ly, J.-F. and Coisne, D. and Lequeux, B. and Le Moal, V. and Mascle, S. and Lotton, P. and Behar, N. and Donal, E. and Thebault, C. and Ridard, C. and Reynaud, A. and Basquin, A. and Bauer, F. and Codjia, R. and Galinier, M. and Tourikis, P. and Stavroula, M. and Tousoulis, D. and Stefanadis, C. and Chrysohoou, C. and Kotrogiannis, I. and Matzaraki, V. and Dimitroula, T. and Karavidas, A. and Tsitsinakis, G. and Kapelios, C. and Nanas, J. and Kampouri, H. and Nana, E. and Kaldara, E. and Eugenidou, A. and Vardas, P. and Saloustros, I. and Patrianakos, A. and Tsaknakis, T. and Evangelou, S. and Nikoloulis, N. and Tziourganou, H. and Tsaroucha, A. and Papadopoulou, A. and Douras, A. and Polgar, L. and Kosztin, A. and Nyolczas, N. and Nagy, A.C. and Halmosi, R. and Elber, J. and Alony, I. and Shotan, A. and Fuhrmann, A.V. and Amir, O. and Romano, S. and Marcon, S. and Penco, M. and Di Mauro, M. and Lemme, E. and Carubelli, V. and Rovetta, R. and Bulgari, M. and Quinzani, F. and Lombardi, C. and Bosi, S. and Schiavina, G. and Squeri, A. and Barbieri, A. and Di Tano, G. and Pirelli, S. and Ferrari, R. and Fucili, A. and Passero, T. and Musio, S. and Di Biase, M. and Correale, M. and Salvemini, G. and Brognoli, S. and Zanelli, E. and Giordano, A. and Agostoni, P. and Italiano, G. and Salvioni, E. and Copelli, S. and Modena, M.G. and Reggianini, L. and Valenti, C. and Olaru, A. and Bandino, S. and Deidda, M. and Mercuro, G. and Dessalvi, C.C. and Marino, P.N. and Di Ruocco, M.V. and Sartori, C. and Piccinino, C. and Parrinello, G. and Licata, G. and Torres, D. and Giambanco, S. and Busalacchi, S. and Arrotti, S. and Novo, S. and Inciardi, R.M. and Pieri, P. and Chirco, P.R. and Galifi, M.A. and Teresi, G. and Buccheri, D. and Minacapelli, A. and Veniani, M. and Frisinghelli, A. and Priori, S.G. and Cattaneo, S. and Opasich, C. and Gualco, A. and Pagliaro, M. and Mancone, M. and Fedele, F. and Cinque, A. and Vellini, M. and Scarfo, I. and Romeo, F. and Ferraiuolo, F. and Sergi, D. and Anselmi, M. and Melandri, F. and Leci, E. and Iori, E. and Bovolo, V. and Pidello, S. and Frea, S. and Bergerone, S. and Botta, M. and Canavosio, F.G. and Gaita, F. and Merlo, M. and Cinquetti, M. and Sinagra, G. and Ramani, F. and Fabris, E. and Stolfo, D. and Artico, J. and Miani, D. and Fresco, C. and Daneluzzi, C. and Proclemer, A. and Cicoira, M. and Zanolla, L. and Marchese, G. and Torelli, F. and Vassanelli, C. and Voronina, N. and Tamakauskas, V. and Smalinskas, V. and Karaliute, R. and Petraskiene, I. and Kazakauskaite, E. and Rumbinaite, E. and Kavoliuniene, A. and Vysniauskas, V. and Brazyte-Ramanauskiene, R. and Petraskiene, D. and Stankala, S. and Switala, P. and Juszczyk, Z. and Sinkiewicz, W. and Gilewski, W. and Pietrzak, J. and Orzel, T. and Kasztelowicz, P. and Kardaszewicz, P. and Lazorko-Piega, M. and Gabryel, J. and Mosakowska, K. and Bellwon, J. and Rynkiewicz, A. and Raczak, G. and Lewicka, E. and Dabrowska-Kugacka, A. and 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Gracia-Rodenas, M.R. and Garrido-Bravo, I.P. and Pastor-Perez, F. and Pascual-Figal, D.A. and Molina, B.D. and Orus, J. and Gonzalo, F.E. and Bertomeu, V. and Valero, R. and Martinez-Abellan, R. and Quiles, J. and Rodrigez-Ortega, J.A. and Mateo, I. and ElAmrani, A. and Fernandez-Vivancos, C. and Valero, D.B. and Almenar-Bonet, L. and Sanchez-Lazaro, I.J. and Marques-Sule, E. and Facila-Rubio, L. and Perez-Silvestre, J. and Garcia-Gonzalez, P. and Ridocci-Soriano, F. and Garcia-Escriva, D. and Pellicer-Cabo, A. and de la Fuente Galan, L. and Diaz, J.L. and Platero, A.R. and Arias, J.C. and Blasco-Peiro, T. and Julve, M.S. and Sanchez-Insa, E. and Aured-Guallar, C. and Portoles-Ocampo, A. and Melin, M. and Hägglund, E. and Stenberg, A. and Lindahl, I.-M. and Asserlund, B. and Olsson, L. and Dahlström, U. and Afzelius, M. and Karlström, P. and Tengvall, L. and Olsson, B. and Kalayci, S. and Temizhan, A. and Cavusoglu, Y. and Gencer, E. and Yilmaz, M.B. and Gunes, H.",
    journal = "European Journal of Heart Failure",
    year = "2020",
    volume = "22",
    number = "8",
    pages = "1378-1389",
    publisher = "John Wiley and Sons Ltd",
    doi = "10.1002/ejhf.1793",
    keywords = "angiotensin receptor antagonist;  dipeptidyl carboxypeptidase inhibitor;  mineralocorticoid antagonist;  aldosterone;  angiotensin derivative;  angiotensin receptor antagonist;  dipeptidyl carboxypeptidase inhibitor;  mineralocorticoid antagonist;  renin, adult;  aged;  all cause mortality;  Article;  cardiovascular mortality;  clinical outcome;  controlled study;  disease association;  disease registry;  drug use;  drug withdrawal;  female;  follow up;  heart failure;  heart failure with preserved ejection fraction;  heart failure with reduced ejection fraction;  human;  hyperkalemia;  low drug dose;  major clinical study;  male;  middle aged;  observational study;  outcome assessment;  outpatient;  prescription;  priority journal;  risk assessment;  risk factor;  systolic blood pressure;  treatment withdrawal;  heart failure;  hyperkalemia;  register, Aldosterone;  Angiotensin Receptor Antagonists;  Angiotensin-Converting Enzyme Inhibitors;  Angiotensins;  Heart Failure;  Humans;  Hyperkalemia;  Mineralocorticoid Receptor Antagonists;  Registries;  Renin",
    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. © 2020 European Society of Cardiology"
}