@article{3104139,
    title = "Association between loop diuretic dose changes and outcomes in chronic heart failure: observations from the ESC-EORP Heart Failure Long-Term Registry",
    author = "Kapelios, C.J. and Laroche, C. and Crespo-Leiro, M.G. and Anker, S.D. and Coats, A.J.S. and Díaz-Molina, B. and Filippatos, G. and Lainscak, M. and Maggioni, A.P. and McDonagh, T. and Mebazaa, A. and Metra, M. and Moura, B. and Mullens, W. and Piepoli, M.F. and Rosano, G.M.C. and Ruschitzka, F. and Seferovic, P.M. and Lund, L.H. and Gale, C.P. and Beleslin, B. and Budaj, A. and Chioncel, O. and Dagres, N. and Danchin, N. and Erlinge, D. and Emberson, J. and Glikson, M. and Gray, A. and Kayikcioglu, M. and Maggioni, A. and Nagy, K.V. and Nedoshivin, A. and Petronio, A.-S. and Roos-Hesselink, J. and Wallentin, L. and Zeymer, U. 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 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 Jimenez, J.F.D. and Harjola, V.-P. and Logeart, D. and Tousoulis, D. and Milicic, D. and Merkely, B. and Amir, O. and Shotan, A. and Shafie, D. and Mirrakhimov, E. and Kavoliuniene, A. and Erglis, A. and Otljanska, M. and Kostovska, E.S. and DeMarco, D.C. and Drozdz, J. and Fonseca, C. and Chioncel, O. and Dekleva, M. and Dahlstrom, U. and Lainscak, M. and Goncalvesova, E. 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 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 Kurteva, T. and Gatzov, P. and Kamenova, D. and Antova, M. and Krejci, J. and Spinar, J. and Krupicka, J. and Malek, F. and Hegarova, M. and Lazarova, M. and Monhart, Z. and Hassanein, M. and El Messiry, F. and El Shazly, A.H. and Elrakshy, Y. and Youssef, A. and Moneim, A.A. and Noamany, M. and Dayem, T.K.A. and Farag, N. and Halawa, S.I. and Hamid, M.A. and Saleh, A. and Ebeid, H. and Hanna, 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 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 Thevenin, S. and Hagege, A. 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 Ridard, C. and Reynaud, A. and Basquin, A. and Bauer, F. and Codjia, R. and Galinier, M. and Tourikis, P. and Stavroula, M. and Stefanadis, C. and Chrysohoou, C. and Kotrogiannis, I. and Matzaraki, V. 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 Tsaknakis, T. and Evangelou, S. 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 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 Bosi, S. and Schiavina, G. and Squeri, 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 Salvioni, E. and Copelli, S. and Modena, M.G. and Valenti, C. and Olaru, A. and Bandino, S. and Deidda, M. and Mercuro, G. and Marino, P.N. and Di Ruocco, M.V. 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 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 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 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 Rumbinaite, E. and Kavoliuniene, A. and Brazyte-Ramanauskiene, R. and Petraskiene, D. and Sinkiewicz, W. and Gilewski, W. and Pietrzak, J. and Orzel, T. and Kardaszewicz, P. and Lazorko-Piega, M. and Mosakowska, K. and Bellwon, J. and Rynkiewicz, A. and Raczak, G. and Lewicka, E. and Dabrowska-Kugacka, A. and Bartkowiak, R. and Wozakowska-Kaplon, B. and Krzeminski, A. and Zabojszcz, M. and Grzegorzko, A. and Bury, K. and Nessler, J. and Zalewski, J. and Furman, A. and Poliwczak, A. and Bala, A. and Zycinski, P. and Rudzinska, M. and Jankowski, L. and Kasprzak, J.D. and Michalak, L. and Soska, K.W. and Drozdz, J. and Huziuk, I. and Flis, P. and Weglarz, J. and Bodys, A. and Grajek, S. and Straburzynska-Migaj, E. and Dankowski, R. and Szymanowska, K. and Szyszka, A. and Nowicka, A. and Samcik, M. and Wolniewicz, L. and Komorowska, K. and Poprawa, I. and Komorowska, E. and Sajnaga, D. and Zolbach, A. and Abdulkarim, A.-F. and Lauko-Rachocka, A. and Kaminski, L. and Kostka, A. and Cichy, A. and Ruszkowski, P. and Splawski, M. and Fitas, G. and Szymczyk, A. and Serwicka, A. and Fiega, A. and Zysko, D. and Krysiak, W. and Szabowski, S. and Skorek, E. and Pruszczyk, P. and Bienias, P. and Ciurzynski, M. 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Campelo, M. and Silva-Cardoso, J. and Rodrigues, J. and Rangel, I. and Martins, E. and Peres, M. and Marta, L. and Severino, D. and Durao, D. and Leao, S. and Magalhaes, P. and Moreira, I. and Ferreira, C. and Araujo, C. and Ferreira, A. and Baptista, A. and Radoi, M. and Bicescu, G. and Vinereanu, D. and Sinescu, C.-J. and Macarie, C. and Popescu, R. and Daha, I. and Dan, G.-A. and Stanescu, C. and Dan, A. and Craiu, E. and Nechita, E. and Christodorescu, R. and Otasevic, P. and Seferovic, P.M. and Simeunovic, D. and Ristic, A.D. and Celic, V. and Pavlovic-Kleut, M. and Stojcevski, B. and Pencic, B. and Stevanovic, A. and Andric, A. and Simić, D. and Ašanin, M. and Iric-Cupic, V. and Jovic, M. and Milanov, S. and Mitic, V. and Atanaskovic, V. and Antic, S. and Pavlovic, M. and Stanojevic, D. and Stoickov, V. and Ilic, S. and DeljaninIlic, M. and Petrovic, D. and Stojsic, S. and Kecojevic, S. and Dodic, S. and Adic, N.C. and Cankovic, M. and Stojiljkovic, J. and Mihajlovic, B. and 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Conde, A.C. and Araujo, A. and Soria, T. and Gomez-Bueno, M. and Cobo-Marcos, M. and Alonso-Pulpon, L. and SegoviaCubero, J. and Sayago, I. and Gonzalez-Segovia, A. and Briceno, A. and Subias, P.E. and Cano, M.J.R. and Sanchez, M.A.G. and Jimenez, J.F.D. and Pinilla, J.M.G. and de la Villa, B.G. and Sahuquillo, A. and Marques, R.B. and Calvo, F.T. and Perez-Martinez, M.T. 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 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 Garcia-Escriva, D. and Pellicer-Cabo, A. and de laFuente 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 Portoles-Ocampo, A. and Melin, M. and Hägglund 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 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 = "1424-1437",
    publisher = "John Wiley and Sons Ltd",
    doi = "10.1002/ejhf.1796",
    keywords = "angiotensin receptor antagonist;  beta adrenergic receptor blocking agent;  dipeptidyl carboxypeptidase inhibitor;  diuretic agent;  loop diuretic agent;  mineralocorticoid antagonist;  diuretic agent;  loop diuretic agent, aged;  all cause mortality;  Article;  cardiovascular mortality;  controlled study;  death;  dose response;  drug dose increase;  drug dose reduction;  female;  follow up;  heart failure;  heart failure with midrange ejection fraction;  heart failure with midrange ejection fraction;  heart failure with preserved ejection fraction;  heart failure with reduced ejection fraction;  hospitalization;  human;  incidence;  major clinical study;  male;  mitral valve regurgitation;  New York Heart Association class;  outpatient;  prediction;  priority journal;  sleep disordered breathing;  systolic blood pressure;  treatment outcome;  heart failure;  heart stroke volume;  middle aged;  register, Aged;  Diuretics;  Female;  Heart Failure;  Hospitalization;  Humans;  Male;  Middle Aged;  Registries;  Sodium Potassium Chloride Symporter Inhibitors;  Stroke Volume",
    abstract = "Aims: Guidelines recommend down-titration of loop diuretics (LD) once euvolaemia is achieved. In outpatients with heart failure (HF), we investigated LD dose changes in daily cardiology practice, agreement with guideline recommendations, predictors of successful LD down-titration and association between dose changes and outcomes. Methods and results: We included 8130 HF patients from the ESC-EORP Heart Failure Long-Term Registry. Among patients who had dose decreased, successful decrease was defined as the decrease not followed by death, HF hospitalization, New York Heart Association class deterioration, or subsequent increase in LD dose. Mean age was 66 ± 13 years, 71% men, 62% HF with reduced ejection fraction, 19% HF with mid-range ejection fraction, 19% HF with preserved ejection fraction. Median [interquartile range (IQR)] LD dose was 40 (25–80) mg. LD dose was increased in 16%, decreased in 8.3% and unchanged in 76%. Median (IQR) follow-up was 372 (363–419) days. Diuretic dose increase (vs. no change) was associated with HF death [hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.12–2.08; P = 0.008] and nominally with cardiovascular death (HR 1.25, 95% CI 0.96–1.63; P = 0.103). Decrease of diuretic dose (vs. no change) was associated with nominally lower HF (HR 0.59, 95% CI 0.33–1.07; P = 0.083) and cardiovascular mortality (HR 0.62,. 95% CI 0.38–1.00; P = 0.052). Among patients who had LD dose decreased, systolic blood pressure [odds ratio (OR) 1.11 per 10 mmHg increase, 95% CI 1.01–1.22; P = 0.032], and absence of (i) sleep apnoea (OR 0.24, 95% CI 0.09–0.69; P = 0.008), (ii) peripheral congestion (OR 0.48, 95% CI 0.29–0.80; P = 0.005), and (iii) moderate/severe mitral regurgitation (OR 0.57, 95% CI 0.37–0.87; P = 0.008) were independently associated with successful decrease. Conclusion: Diuretic dose was unchanged in 76% and decreased in 8.3% of outpatients with chronic HF. LD dose increase was associated with worse outcomes, while the LD dose decrease group showed a trend for better outcomes compared with the no-change group. Higher systolic blood pressure, and absence of (i) sleep apnoea, (ii) peripheral congestion, and (iii) moderate/severe mitral regurgitation were independently associated with successful dose decrease. © 2020 European Society of Cardiology"
}