Association between loop diuretic dose changes and outcomes in chronic heart failure: observations from the ESC-EORP Heart Failure Long-Term Registry

Kapelios, C.J.; Laroche, C.; Crespo-Leiro, M.G.; Anker, S.D.; Coats, A.J.S.; Diaz-Molina, B.; Filippatos, G.; Lainscak, M.; Maggioni, A.P.; Mcdonagh, T.; Mebazaa, A.; Metra, M.; Moura, B.; Mullens, W.; Piepoli, M.F.; Rosano, G.M.C.; Ruschitzka, F.; Seferovic, P.M.; Lund, L.H.; Gale, C.P.; Beleslin, B.; Budaj, A.; Chioncel, O.; Dagres, N.; Danchin, N.; Erlinge, D.; Emberson, J.; Glikson, M.; Gray, A.; Kayikcioglu, M.; Maggioni, A.; Nagy, K.V.; Nedoshivin, A.; Petronio, A.-.; Roos-Hesselink, J.; Wallentin, L.; Zeymer, U.; Anker, S.; Mebazaa, A.; Coats, A.; Filippatos, G.; Ferrari, R.; Maggioni, A.P.; Goda, A.; Diez, M.; Fernandez, A.; Fruhwald, F.; Gatzov, P.; Kurlianskaya, A.; Hullin, R.; Christodoulides, T.; Hradec, J.; Nielsen, O.W.; Nedjar, R.; Uuetoa, T.; Jimenez, J.F.D.; Harjola, V.-.; Logeart, D.; Tousoulis, D.; Milicic, D.; Merkely, B.; Amir, O.; Shotan, A.; Shafie, D.; Mirrakhimov, E.; Kavoliuniene, A.; Erglis, A.; Otljanska, M.; Kostovska, E.S.; Demarco, D.C.; Drozdz, J.; Fonseca, C.; Chioncel, O.; Dekleva, M.; Dahlstrom, U.; Lainscak, M.; Goncalvesova, E.; Estrago, V.; Bajraktari, G.; Auer, J.; Ablasser, K.; Fruhwald, F.; Dolze, T.; Brandner, K.; Gstrein, S.; Poelzl, G.; Moertl, D.; Reiter, S.; Muslibegovic, A.; Vasilj, M.; Fazlibegovic, E.; Cesko, M.; Zelenika, D.; Palic, B.; Pravdic, D.; Cuk, D.; Vitlianova, K.; Katova, T.; Kurteva, T.; Gatzov, P.; Kamenova, D.; Antova, M.; Krejci, J.; Spinar, J.; Krupicka, J.; Malek, F.; Hegarova, M.; Lazarova, M.; Monhart, Z.; Hassanein, M.; El Messiry, F.; El Shazly, A.H.; Elrakshy, Y.; Youssef, A.; Moneim, A.A.; Noamany, M.; Dayem, T.K.A.; Farag, N.; Halawa, S.I.; Hamid, M.A.; Saleh, A.; Ebeid, H.; Hanna, R.; Louis, O.; Enen, M.A.; Ibrahim, B.S.; Nasr, G.; Elbahry, A.; Sobhy, H.; Ashmawy, M.; Gouda, M.; Aboleineen, W.; Bernard, Y.; Meneveau, N.; Pillot, M.; Morel, M.; Seronde, M.-.; Schiele, F.; Briand, F.; Delahaye, F.; Damy, T.; Eicher, J.-.; De Groote, P.; Fertin, M.; Lamblin, N.; Isnard, R.; Thevenin, S.; Hagege, A.; Logeart, D.; Le Marcis, V.; J. -F., L.; Coisne, D.; Lequeux, B.; Le Moal, V.; Mascle, S.; Lotton, P.; Behar, N.; Donal, E.; Ridard, C.; Reynaud, A.; Basquin, A.; Bauer, F.; Codjia, R.; Galinier, M.; Tourikis, P.; Stavroula, M.; Stefanadis, C.; Chrysohoou, C.; Kotrogiannis, I.; Matzaraki, V.; Karavidas, A.; Tsitsinakis, G.; Kapelios, C.; Nanas, J.; Kampouri, H.; Nana, E.; Kaldara, E.; Eugenidou, A.; Vardas, P.; Saloustros, I.; Tsaknakis, T.; Evangelou, S.; Tziourganou, H.; Tsaroucha, A.; Papadopoulou, A.; Douras, A.; Polgar, L.; Kosztin, A.; Nyolczas, N.; Nagy, A.C.; Halmosi, R.; Elber, J.; Shotan, A.; Fuhrmann, A.V.; Amir, O.; Romano, S.; Marcon, S.; Penco, M.; Di Mauro, M.; Lemme, E.; Carubelli, V.; Rovetta, R.; Bulgari, M.; Quinzani, F.; Bosi, S.; Schiavina, G.; Squeri, A.; Di Tano, G.; Pirelli, S.; Ferrari, R.; Fucili, A.; Passero, T.; Musio, S.; Di Biase, M.; Correale, M.; Salvemini, G.; Brognoli, S.; Zanelli, E.; Giordano, A.; Agostoni, P.; Salvioni, E.; Copelli, S.; Modena, M.G.; Valenti, C.; Olaru, A.; Bandino, S.; Deidda, M.; Mercuro, G.; Marino, P.N.; Di Ruocco, M.V.; Piccinino, C.; Parrinello, G.; Licata, G.; Torres, D.; Giambanco, S.; Busalacchi, S.; Arrotti, S.; Novo, S.; Inciardi, R.M.; Pieri, P.; Galifi, M.A.; Teresi, G.; Buccheri, D.; Minacapelli, A.; Veniani, M.; Frisinghelli, A.; Priori, S.G.; Cattaneo, S.; Opasich, C.; Gualco, A.; Pagliaro, M.; Mancone, M.; Fedele, F.; Cinque, A.; Vellini, M.; Scarfo, I.; Romeo, F.; Ferraiuolo, F.; Sergi, D.; Anselmi, M.; Melandri, F.; Leci, E.; Iori, E.; Bovolo, V.; Frea, S.; Bergerone, S.; Botta, M.; Canavosio, F.G.; Gaita, F.; Merlo, M.; Cinquetti, M.; Sinagra, G.; Ramani, F.; Fabris, E.; Artico, J.; Miani, D.; Fresco, C.; Daneluzzi, C.; Proclemer, A.; Cicoira, M.; Zanolla, L.; Marchese, G.; Torelli, F.; Vassanelli, C.; Voronina, N.; Tamakauskas, V.; Smalinskas, V.; Karaliute, R.; Petraskiene, I.; Rumbinaite, E.; Kavoliuniene, A.; Brazyte-Ramanauskiene, R.; Petraskiene, D.; Sinkiewicz, W.; Gilewski, W.; Pietrzak, J.; Orzel, T.; Kardaszewicz, P.; Lazorko-Piega, M.; Mosakowska, K.; Bellwon, J.; Rynkiewicz, A.; Raczak, G.; Lewicka, E.; Dabrowska-Kugacka, A.; Bartkowiak, R.; Wozakowska-Kaplon, B.; Krzeminski, A.; Zabojszcz, M.; Grzegorzko, A.; Bury, K.; Nessler, J.; Zalewski, J.; Furman, A.; Poliwczak, A.; Bala, A.; Zycinski, P.; Rudzinska, M.; Jankowski, L.; Kasprzak, J.D.; Michalak, L.; Soska, K.W.; Drozdz, J.; Huziuk, I.; Flis, P.; Weglarz, J.; Bodys, A.; Grajek, S.; Straburzynska-Migaj, E.; Dankowski, R.; Szymanowska, K.; Szyszka, A.; Nowicka, A.; Samcik, M.; Wolniewicz, L.; Komorowska, K.; Poprawa, I.; Komorowska, E.; Sajnaga, D.; Zolbach, A.; Abdulkarim, A.-.; Lauko-Rachocka, A.; Kaminski, L.; Kostka, A.; Cichy, A.; Ruszkowski, P.; Splawski, M.; Fitas, G.; Szymczyk, A.; Serwicka, A.; Fiega, A.; Zysko, D.; Krysiak, W.; Szabowski, S.; Skorek, E.; Pruszczyk, P.; Bienias, P.; Ciurzynski, M.; Welnicki, M.; Mamcarz, A.; Folga, A.; Zielinski, T.; Rywik, T.; Leszek, P.; Sobieszczanska-Malek, M.; Kozar-Kaminska, K.; Komuda, K.; Wisniewska, J.; Tarnowska, A.; Marchel, M.; Opolski, G.; Kaplon-Cieslicka, A.; Gil, R.J.; Mozenska, O.; Gil, K.; Pawlak, A.; Michalek, A.; Krzesinski, P.; Piotrowicz, K.; Stanczyk, A.; Skrobowski, A.; Ponikowski, P.; Jankowska, E.; Rozentryt, P.; Polonski, L.; Nowalany-Kozielska, E.; Kuczaj, A.; Kalarus, Z.; Szulik, M.; Klys, J.; Prokop-Lewicka, G.; Kleinrok, A.; Tavaresaguiar, C.; Ventosa, A.; Pereira, S.; Faria, R.; Chin, J.; Dejesus, I.; Santos, R.; Silva, P.; Moreno, N.; Lourenco, C.; Pereira, A.; Castro, A.; Andrade, A.; Oliveiraguimaraes, T.; Martins, S.; Placido, R.; Lima, G.; Brito, D.; Francisco, A.R.; Proenca, M.; Araujo, I.; Marques, F.; Fonseca, C.; Moura, B.; Campelo, M.; Silva-Cardoso, J.; Rodrigues, J.; Rangel, I.; Martins, E.; Peres, M.; Marta, L.; Severino, D.; Durao, D.; Leao, S.; Magalhaes, P.; Moreira, I.; Ferreira, C.; Araujo, C.; Ferreira, A.; Baptista, A.; Radoi, M.; Bicescu, G.; Vinereanu, D.; Sinescu, C.-.; Macarie, C.; Popescu, R.; Daha, I.; Dan, G.-.; Stanescu, C.; Dan, A.; Craiu, E.; Nechita, E.; Christodorescu, R.; Otasevic, P.; Seferovic, P.M.; Simeunovic, D.; Ristic, A.D.; Celic, V.; Pavlovic-Kleut, M.; Stojcevski, B.; Pencic, B.; Stevanovic, A.; Andric, A.; Simic, D.; Asanin, M.; Iric-Cupic, V.; Jovic, M.; Milanov, S.; Mitic, V.; Atanaskovic, V.; Antic, S.; Pavlovic, M.; Stanojevic, D.; Stoickov, V.; Ilic, S.; Deljaninilic, M.; Petrovic, D.; Stojsic, S.; Kecojevic, S.; Dodic, S.; Adic, N.C.; Cankovic, M.; Stojiljkovic, J.; Mihajlovic, B.; Radin, A.; Radovanovic, S.; Krotin, M.; Klabnik, A.; Pernicky, M.; Murin, J.; Kovar, F.; Kmec, J.; Strasek, M.; Iskra, M.S.; Ravnikar, T.; Suligoj, N.C.; Fras, Z.; Jug, B.; Glavic, T.; Losic, R.; Bombek, M.; Krunic, B.; Horvat, S.; Kovac, D.; Rajtman, D.; Letonja, M.; Winkler, R.; Melihen-Bartolic, C.; Bartolic, A.; Kladnik, M.; Pusnik, C.S.; Marolt, A.; Klen, J.; Drnovsek, B.; Leskovar, B.; Anguita, M.J.F.; Gallegopage, J.C.; Martinez, F.M.S.; Andres, J.; Bayes-Genis, A.; Mirabet, S.; Mendez, A.; Garcia-Cosio, L.; Leon, V.; Gonzalez-Costello, J.; Muntane, G.; Garay, A.; Alcade-Martinez, V.; Fernandez, S.L.; Rivera-Lopez, R.; Fernandez-Alvarez, M.; Serrano-Martinez, J.L.; Grille-Cancela, Z.; Marzoa-Rivas, R.; Paniagua-Martin, M.J.; Barge-Caballero, E.; Gonzalez-Gallarza, R.D.; Salvadormontanes, O.; Manjavacas, A.M.I.; Conde, A.C.; Araujo, A.; Soria, T.; Gomez-Bueno, M.; Cobo-Marcos, M.; Alonso-Pulpon, L.; Segoviacubero, J.; Sayago, I.; Gonzalez-Segovia, A.; Briceno, A.; Subias, P.E.; Cano, M.J.R.; Sanchez, M.A.G.; Jimenez, J.F.D.; Pinilla, J.M.G.; De La Villa, B.G.; Sahuquillo, A.; Marques, R.B.; Calvo, F.T.; Perez-Martinez, M.T.; Garrido-Bravo, I.P.; Pastor-Perez, F.; Pascual-Figal, D.A.; Molina, B.D.; Orus, J.; Gonzalo, F.E.; Bertomeu, V.; Valero, R.; Martinez-Abellan, R.; Quiles, J.; Mateo, I.; Elamrani, A.; Fernandez-Vivancos, C.; Valero, D.B.; Almenar-Bonet, L.; Sanchez-Lazaro, I.J.; Marques-Sule, E.; Facila-Rubio, L.; Perez-Silvestre, J.; Garcia-Gonzalez, P.; Garcia-Escriva, D.; Pellicer-Cabo, A.; De Lafuente Galan, L.; Diaz, J.L.; Platero, A.R.; Arias, J.C.; Blasco-Peiro, T.; Julve, M.S.; Sanchez-Insa, E.; Portoles-Ocampo, A.; Melin, M.; Hagglund,; Lindahl, I.-.; Asserlund, B.; Olsson, L.; Dahlstrom, U.; Afzelius, M.; Karlstrom, P.; Tengvall, L.; Olsson, B.; Kalayci, S.; Cavusoglu, Y.; Gencer, E.; Yilmaz, M.B.; Gunes, H.

doi:10.1002/ejhf.1796

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.

Association between loop diuretic dose changes and outcomes in chronic heart failure: observations from the ESC-EORP Heart Failure Long-Term Registry / C.J. Kapelios, C. Laroche, M.G. Crespo-Leiro, S.D. Anker, A.J.S. Coats, B. Diaz-Molina, G. Filippatos, M. Lainscak, A.P. Maggioni, T. McDonagh, A. Mebazaa, M. Metra, B. Moura, W. Mullens, M.F. Piepoli, G.M.C. Rosano, F. Ruschitzka, P.M. Seferovic, L.H. Lund, C.P. Gale, B. Beleslin, A. Budaj, O. Chioncel, N. Dagres, N. Danchin, D. Erlinge, J. Emberson, M. Glikson, A. Gray, M. Kayikcioglu, A. Maggioni, K.V. Nagy, A. Nedoshivin, A.-. Petronio, J. Roos-Hesselink, L. Wallentin, U. Zeymer, S. Anker, A. Mebazaa, A. Coats, G. Filippatos, R. Ferrari, A.P. Maggioni, A. Goda, M. Diez, A. Fernandez, F. Fruhwald, P. Gatzov, A. Kurlianskaya, R. Hullin, T. Christodoulides, J. Hradec, O.W. Nielsen, R. Nedjar, T. Uuetoa, J.F.D. Jimenez, V.-. Harjola, D. Logeart, D. Tousoulis, D. Milicic, B. Merkely, O. Amir, A. Shotan, D. Shafie, E. Mirrakhimov, A. Kavoliuniene, A. Erglis, M. Otljanska, E.S. Kostovska, D.C. DeMarco, J. Drozdz, C. Fonseca, O. Chioncel, M. Dekleva, U. Dahlstrom, M. Lainscak, E. Goncalvesova, V. Estrago, G. Bajraktari, J. Auer, K. Ablasser, F. Fruhwald, T. Dolze, K. Brandner, S. Gstrein, G. Poelzl, D. Moertl, S. Reiter, A. Muslibegovic, M. Vasilj, E. Fazlibegovic, M. Cesko, D. Zelenika, B. Palic, D. Pravdic, D. Cuk, K. Vitlianova, T. Katova, T. Kurteva, P. Gatzov, D. Kamenova, M. Antova, J. Krejci, J. Spinar, J. Krupicka, F. Malek, M. Hegarova, M. Lazarova, Z. Monhart, M. Hassanein, F. El Messiry, A.H. El Shazly, Y. Elrakshy, A. Youssef, A.A. Moneim, M. Noamany, T.K.A. Dayem, N. Farag, S.I. Halawa, M.A. Hamid, A. Saleh, H. Ebeid, R. Hanna, O. Louis, M.A. Enen, B.S. Ibrahim, G. Nasr, A. Elbahry, H. Sobhy, M. Ashmawy, M. Gouda, W. Aboleineen, Y. Bernard, N. Meneveau, M. Pillot, M. Morel, M.-. Seronde, F. Schiele, F. Briand, F. Delahaye, T. Damy, J.-. Eicher, P. de Groote, M. Fertin, N. Lamblin, R. Isnard, S. Thevenin, A. Hagege, D. Logeart, V. Le Marcis, J.-. Ly, D. Coisne, B. Lequeux, V. Le Moal, S. Mascle, P. Lotton, N. Behar, E. Donal, C. Ridard, A. Reynaud, A. Basquin, F. Bauer, R. Codjia, M. Galinier, P. Tourikis, M. Stavroula, C. Stefanadis, C. Chrysohoou, I. Kotrogiannis, V. Matzaraki, A. Karavidas, G. Tsitsinakis, C. Kapelios, J. Nanas, H. Kampouri, E. Nana, E. Kaldara, A. Eugenidou, P. Vardas, I. Saloustros, T. Tsaknakis, S. Evangelou, H. Tziourganou, A. Tsaroucha, A. Papadopoulou, A. Douras, L. Polgar, A. Kosztin, N. Nyolczas, A.C. Nagy, R. Halmosi, J. Elber, A. Shotan, A.V. Fuhrmann, O. Amir, S. Romano, S. Marcon, M. Penco, M. Di Mauro, E. Lemme, V. Carubelli, R. Rovetta, M. Bulgari, F. Quinzani, S. Bosi, G. Schiavina, A. Squeri, G. Di Tano, S. Pirelli, R. Ferrari, A. Fucili, T. Passero, S. Musio, M. Di Biase, M. Correale, G. Salvemini, S. Brognoli, E. Zanelli, A. Giordano, P. Agostoni, E. Salvioni, S. Copelli, M.G. Modena, C. Valenti, A. Olaru, S. Bandino, M. Deidda, G. Mercuro, P.N. Marino, M.V. Di Ruocco, C. Piccinino, G. Parrinello, G. Licata, D. Torres, S. Giambanco, S. Busalacchi, S. Arrotti, S. Novo, R.M. Inciardi, P. Pieri, M.A. 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. Frea, S. Bergerone, M. Botta, F.G. Canavosio, F. Gaita, M. Merlo, M. Cinquetti, G. Sinagra, F. Ramani, E. Fabris, 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. Rumbinaite, A. Kavoliuniene, R. Brazyte-Ramanauskiene, D. Petraskiene, W. Sinkiewicz, W. Gilewski, J. Pietrzak, T. Orzel, P. Kardaszewicz, M. Lazorko-Piega, K. Mosakowska, J. Bellwon, A. Rynkiewicz, G. Raczak, E. Lewicka, A. Dabrowska-Kugacka, R. Bartkowiak, B. Wozakowska-Kaplon, A. Krzeminski, M. Zabojszcz, A. Grzegorzko, K. Bury, J. Nessler, J. Zalewski, A. Furman, A. Poliwczak, A. Bala, P. Zycinski, M. Rudzinska, L. Jankowski, J.D. Kasprzak, L. Michalak, K.W. Soska, J. Drozdz, I. Huziuk, P. Flis, J. Weglarz, A. Bodys, S. Grajek, E. Straburzynska-Migaj, R. Dankowski, K. Szymanowska, A. Szyszka, A. Nowicka, M. Samcik, L. Wolniewicz, K. Komorowska, I. Poprawa, E. Komorowska, D. Sajnaga, A. Zolbach, A.-. 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, K. Kozar-Kaminska, K. Komuda, J. Wisniewska, A. Tarnowska, M. Marchel, G. Opolski, A. Kaplon-Cieslicka, R.J. Gil, O. Mozenska, K. Gil, A. Pawlak, A. Michalek, P. Krzesinski, K. Piotrowicz, A. Stanczyk, A. Skrobowski, P. Ponikowski, E. Jankowska, P. Rozentryt, L. Polonski, E. Nowalany-Kozielska, A. Kuczaj, Z. Kalarus, M. Szulik, J. Klys, G. Prokop-Lewicka, A. Kleinrok, C. TavaresAguiar, A. Ventosa, S. Pereira, R. Faria, J. Chin, I. DeJesus, R. Santos, P. Silva, N. Moreno, C. Lourenco, A. Pereira, A. Castro, A. Andrade, T. OliveiraGuimaraes, S. Martins, R. Placido, G. Lima, D. Brito, A.R. Francisco, M. Proenca, I. Araujo, F. Marques, C. Fonseca, B. Moura, M. Campelo, J. Silva-Cardoso, J. Rodrigues, I. Rangel, E. Martins, M. Peres, L. Marta, D. Severino, D. Durao, S. Leao, P. Magalhaes, I. Moreira, C. Ferreira, C. Araujo, A. Ferreira, A. Baptista, M. Radoi, G. Bicescu, D. Vinereanu, C.-. Sinescu, C. Macarie, R. Popescu, I. Daha, G.-. Dan, C. Stanescu, A. Dan, E. Craiu, E. Nechita, R. Christodorescu, P. Otasevic, P.M. Seferovic, D. Simeunovic, A.D. Ristic, V. Celic, M. Pavlovic-Kleut, B. Stojcevski, B. Pencic, A. Stevanovic, A. Andric, D. Simic, M. Asanin, V. Iric-Cupic, M. Jovic, S. Milanov, V. Mitic, V. Atanaskovic, S. Antic, M. Pavlovic, D. Stanojevic, V. Stoickov, S. Ilic, M. DeljaninIlic, D. Petrovic, S. Stojsic, S. Kecojevic, S. Dodic, N.C. Adic, M. Cankovic, J. Stojiljkovic, B. Mihajlovic, A. Radin, S. Radovanovic, M. Krotin, A. Klabnik, M. Pernicky, J. Murin, F. Kovar, J. Kmec, M. Strasek, M.S. Iskra, T. Ravnikar, N.C. Suligoj, Z. Fras, B. Jug, T. Glavic, R. Losic, M. Bombek, B. Krunic, S. Horvat, D. Kovac, D. Rajtman, M. Letonja, R. Winkler, C. Melihen-Bartolic, A. Bartolic, M. Kladnik, C.S. Pusnik, A. Marolt, J. Klen, B. Drnovsek, B. Leskovar, M.J.F. Anguita, J.C. GallegoPage, F.M.S. Martinez, J. Andres, A. Bayes-Genis, S. Mirabet, A. Mendez, L. Garcia-Cosio, V. Leon, J. Gonzalez-Costello, G. Muntane, A. Garay, V. Alcade-Martinez, S.L. Fernandez, R. Rivera-Lopez, M. Fernandez-Alvarez, J.L. Serrano-Martinez, Z. Grille-Cancela, R. Marzoa-Rivas, M.J. Paniagua-Martin, E. Barge-Caballero, R.D. Gonzalez-Gallarza, O. SalvadorMontanes, A.M.I. Manjavacas, A.C. Conde, A. Araujo, T. Soria, M. Gomez-Bueno, M. Cobo-Marcos, L. Alonso-Pulpon, J. SegoviaCubero, I. Sayago, A. Gonzalez-Segovia, A. Briceno, P.E. Subias, M.J.R. Cano, M.A.G. Sanchez, J.F.D. Jimenez, J.M.G. Pinilla, B.G. de la Villa, A. Sahuquillo, R.B. Marques, F.T. Calvo, M.T. Perez-Martinez, I.P. Garrido-Bravo, F. Pastor-Perez, D.A. Pascual-Figal, B.D. Molina, J. Orus, F.E. Gonzalo, V. Bertomeu, R. Valero, R. Martinez-Abellan, J. Quiles, I. Mateo, A. ElAmrani, C. Fernandez-Vivancos, D.B. Valero, L. Almenar-Bonet, I.J. Sanchez-Lazaro, E. Marques-Sule, L. Facila-Rubio, J. Perez-Silvestre, P. Garcia-Gonzalez, D. Garcia-Escriva, A. Pellicer-Cabo, L. de laFuente Galan, J.L. Diaz, A.R. Platero, J.C. Arias, T. Blasco-Peiro, M.S. Julve, E. Sanchez-Insa, A. Portoles-Ocampo, M. Melin, Hagglund, I.-. Lindahl, B. Asserlund, L. Olsson, U. Dahlstrom, M. Afzelius, P. Karlstrom, L. Tengvall, B. Olsson, S. Kalayci, Y. Cavusoglu, E. Gencer, M.B. Yilmaz, H. Gunes. - In: EUROPEAN JOURNAL OF HEART FAILURE. - ISSN 1388-9842. - 22:8(2020 Jun), pp. 1424-1437. [10.1002/ejhf.1796]

Association between loop diuretic dose changes and outcomes in chronic heart failure: observations from the ESC-EORP Heart Failure Long-Term Registry

Kapelios C. J.;Laroche C.;Crespo-Leiro M. G.;Anker S. D.;Coats A. J. S.;Diaz-Molina B.;Filippatos G.;Lainscak M.;Maggioni A. P.;McDonagh T.;Mebazaa A.;Metra M.;Moura B.;Mullens W.;Piepoli M. F.;Rosano G. M. C.;Ruschitzka F.;Seferovic P. M.;Lund L. H.;Gale C. P.;Beleslin B.;Budaj A.;Chioncel O.;Dagres N.;Danchin N.;Erlinge D.;Emberson J.;Glikson M.;Gray A.;Kayikcioglu M.;Maggioni A.;Nagy K. V.;Nedoshivin A.;Petronio A. -S.;Roos-Hesselink J.;Wallentin L.;Zeymer U.;Anker S.;Mebazaa A.;Coats A.;Filippatos G.;Ferrari R.;Maggioni A. P.;Goda A.;Diez M.;Fernandez A.;Fruhwald F.;Gatzov P.;Kurlianskaya A.;Hullin R.;Christodoulides T.;Hradec J.;Nielsen O. W.;Nedjar R.;Uuetoa T.;Jimenez J. F. D.;Harjola V. -P.;Logeart D.;Tousoulis D.;Milicic D.;Merkely B.;Amir O.;Shotan A.;Shafie D.;Mirrakhimov E.;Kavoliuniene A.;Erglis A.;Otljanska M.;Kostovska E. S.;DeMarco D. C.;Drozdz J.;Fonseca C.;Chioncel O.;Dekleva M.;Dahlstrom U.;Lainscak M.;Goncalvesova E.;Estrago V.;Bajraktari G.;Auer J.;Ablasser K.;Fruhwald F.;Dolze T.;Brandner K.;Gstrein S.;Poelzl G.;Moertl D.;Reiter S.;Muslibegovic A.;Vasilj M.;Fazlibegovic E.;Cesko M.;Zelenika D.;Palic B.;Pravdic D.;Cuk D.;Vitlianova K.;Katova T.;Kurteva T.;Gatzov P.;Kamenova D.;Antova M.;Krejci J.;Spinar J.;Krupicka J.;Malek F.;Hegarova M.;Lazarova M.;Monhart Z.;Hassanein M.;El Messiry F.;El Shazly A. H.;Elrakshy Y.;Youssef A.;Moneim A. A.;Noamany M.;Dayem T. K. A.;Farag N.;Halawa S. I.;Hamid M. A.;Saleh A.;Ebeid H.;Hanna R.;Louis O.;Enen M. A.;Ibrahim B. S.;Nasr G.;Elbahry A.;Sobhy H.;Ashmawy M.;Gouda M.;Aboleineen W.;Bernard Y.;Meneveau N.;Pillot M.;Morel M.;Seronde M. -F.;Schiele F.;Briand F.;Delahaye F.;Damy T.;Eicher J. -C.;de Groote P.;Fertin M.;Lamblin N.;Isnard R.;Thevenin S.;Hagege A.;Logeart D.;Le Marcis V.;Ly J. -F.;Coisne D.;Lequeux B.;Le Moal V.;Mascle S.;Lotton P.;Behar N.;Donal E.;Ridard C.;Reynaud A.;Basquin A.;Bauer F.;Codjia R.;Galinier M.;Tourikis P.;Stavroula M.;Stefanadis C.;Chrysohoou C.;Kotrogiannis I.;Matzaraki V.;Karavidas A.;Tsitsinakis G.;Kapelios C.;Nanas J.;Kampouri H.;Nana E.;Kaldara E.;Eugenidou A.;Vardas P.;Saloustros I.;Tsaknakis T.;Evangelou S.;Tziourganou H.;Tsaroucha A.;Papadopoulou A.;Douras A.;Polgar L.;Kosztin A.;Nyolczas N.;Nagy A. C.;Halmosi R.;Elber J.;Shotan A.;Fuhrmann A. V.;Amir O.;Romano S.;Marcon S.;Penco M.;Di Mauro M.;Lemme E.;Carubelli V.;Rovetta R.;Bulgari M.;Quinzani F.;Bosi S.;Schiavina G.;Squeri A.;Di Tano G.;Pirelli S.;Ferrari R.;Fucili A.;Passero T.;Musio S.;Di Biase M.;Correale M.;Salvemini G.;Brognoli S.;Zanelli E.;Giordano A.;P. Agostoni^{Membro del Collaboration Group};Salvioni E.;Copelli S.;Modena M. G.;Valenti C.;Olaru A.;Bandino S.;Deidda M.;Mercuro G.;Marino P. N.;Di Ruocco M. V.;Piccinino C.;Parrinello G.;Licata G.;Torres D.;Giambanco S.;Busalacchi S.;Arrotti S.;Novo S.;Inciardi R. M.;Pieri P.;Galifi M. A.;Teresi G.;Buccheri D.;Minacapelli A.;Veniani M.;Frisinghelli A.;Priori S. G.;Cattaneo S.;Opasich C.;Gualco A.;Pagliaro M.;Mancone M.;Fedele F.;Cinque A.;Vellini M.;Scarfo I.;Romeo F.;Ferraiuolo F.;Sergi D.;Anselmi M.;Melandri F.;Leci E.;Iori E.;Bovolo V.;Frea S.;Bergerone S.;Botta M.;Canavosio F. G.;Gaita F.;Merlo M.;Cinquetti M.;Sinagra G.;Ramani F.;Fabris E.;Artico J.;Miani D.;Fresco C.;Daneluzzi C.;Proclemer A.;Cicoira M.;Zanolla L.;Marchese G.;Torelli F.;Vassanelli C.;Voronina N.;Tamakauskas V.;Smalinskas V.;Karaliute R.;Petraskiene I.;Rumbinaite E.;Kavoliuniene A.;Brazyte-Ramanauskiene R.;Petraskiene D.;Sinkiewicz W.;Gilewski W.;Pietrzak J.;Orzel T.;Kardaszewicz P.;Lazorko-Piega M.;Mosakowska K.;Bellwon J.;Rynkiewicz A.;Raczak G.;Lewicka E.;Dabrowska-Kugacka A.;Bartkowiak R.;Wozakowska-Kaplon B.;Krzeminski A.;Zabojszcz M.;Grzegorzko A.;Bury K.;Nessler J.;Zalewski J.;Furman A.;Poliwczak A.;Bala A.;Zycinski P.;Rudzinska M.;Jankowski L.;Kasprzak J. D.;Michalak L.;Soska K. W.;Drozdz J.;Huziuk I.;Flis P.;Weglarz J.;Bodys A.;Grajek S.;Straburzynska-Migaj E.;Dankowski R.;Szymanowska K.;Szyszka A.;Nowicka A.;Samcik M.;Wolniewicz L.;Komorowska K.;Poprawa I.;Komorowska E.;Sajnaga D.;Zolbach A.;Abdulkarim A. -F.;Lauko-Rachocka A.;Kaminski L.;Kostka A.;Cichy A.;Ruszkowski P.;Splawski M.;Fitas G.;Szymczyk A.;Serwicka A.;Fiega A.;Zysko D.;Krysiak W.;Szabowski S.;Skorek E.;Pruszczyk P.;Bienias P.;Ciurzynski M.;Welnicki M.;Mamcarz A.;Folga A.;Zielinski T.;Rywik T.;Leszek P.;Sobieszczanska-Malek M.;Kozar-Kaminska K.;Komuda K.;Wisniewska J.;Tarnowska A.;Marchel M.;Opolski G.;Kaplon-Cieslicka A.;Gil R. J.;Mozenska O.;Gil K.;Pawlak A.;Michalek A.;Krzesinski P.;Piotrowicz K.;Stanczyk A.;Skrobowski A.;Ponikowski P.;Jankowska E.;Rozentryt P.;Polonski L.;Nowalany-Kozielska E.;Kuczaj A.;Kalarus Z.;Szulik M.;Klys J.;Prokop-Lewicka G.;Kleinrok A.;TavaresAguiar C.;Ventosa A.;Pereira S.;Faria R.;Chin J.;DeJesus I.;Santos R.;Silva P.;Moreno N.;Lourenco C.;Pereira A.;Castro A.;Andrade A.;OliveiraGuimaraes T.;Martins S.;Placido R.;Lima G.;Brito D.;Francisco A. R.;Proenca M.;Araujo I.;Marques F.;Fonseca C.;Moura B.;Campelo M.;Silva-Cardoso J.;Rodrigues J.;Rangel I.;Martins E.;Peres M.;Marta L.;Severino D.;Durao D.;Leao S.;Magalhaes P.;Moreira I.;Ferreira C.;Araujo C.;Ferreira A.;Baptista A.;Radoi M.;Bicescu G.;Vinereanu D.;Sinescu C. -J.;Macarie C.;Popescu R.;Daha I.;Dan G. -A.;Stanescu C.;Dan A.;Craiu E.;Nechita E.;Christodorescu R.;Otasevic P.;Seferovic P. M.;Simeunovic D.;Ristic A. D.;Celic V.;Pavlovic-Kleut M.;Stojcevski B.;Pencic B.;Stevanovic A.;Andric A.;Simic D.;Asanin M.;Iric-Cupic V.;Jovic M.;Milanov S.;Mitic V.;Atanaskovic V.;Antic S.;Pavlovic M.;Stanojevic D.;Stoickov V.;Ilic S.;DeljaninIlic M.;Petrovic D.;Stojsic S.;Kecojevic S.;Dodic S.;Adic N. C.;Cankovic M.;Stojiljkovic J.;Mihajlovic B.;Radin A.;Radovanovic S.;Krotin M.;Klabnik A.;Pernicky M.;Murin J.;Kovar F.;Kmec J.;Strasek M.;Iskra M. S.;Ravnikar T.;Suligoj N. C.;Fras Z.;Jug B.;Glavic T.;Losic R.;Bombek M.;Krunic B.;Horvat S.;Kovac D.;Rajtman D.;Letonja M.;Winkler R.;Melihen-Bartolic C.;Bartolic A.;Kladnik M.;Pusnik C. S.;Marolt A.;Klen J.;Drnovsek B.;Leskovar B.;Anguita M. J. F.;GallegoPage J. C.;Martinez F. M. S.;Andres J.;Bayes-Genis A.;Mirabet S.;Mendez A.;Garcia-Cosio L.;Leon V.;Gonzalez-Costello J.;Muntane G.;Garay A.;Alcade-Martinez V.;Fernandez S. L.;Rivera-Lopez R.;Fernandez-Alvarez M.;Serrano-Martinez J. L.;Grille-Cancela Z.;Marzoa-Rivas R.;Paniagua-Martin M. J.;Barge-Caballero E.;Gonzalez-Gallarza R. D.;SalvadorMontanes O.;Manjavacas A. M. I.;Conde A. C.;Araujo A.;Soria T.;Gomez-Bueno M.;Cobo-Marcos M.;Alonso-Pulpon L.;SegoviaCubero J.;Sayago I.;Gonzalez-Segovia A.;Briceno A.;Subias P. E.;Cano M. J. R.;Sanchez M. A. G.;Jimenez J. F. D.;Pinilla J. M. G.;de la Villa B. G.;Sahuquillo A.;Marques R. B.;Calvo F. T.;Perez-Martinez M. T.;Garrido-Bravo I. P.;Pastor-Perez F.;Pascual-Figal D. A.;Molina B. D.;Orus J.;Gonzalo F. E.;Bertomeu V.;Valero R.;Martinez-Abellan R.;Quiles J.;Mateo I.;ElAmrani A.;Fernandez-Vivancos C.;Valero D. B.;Almenar-Bonet L.;Sanchez-Lazaro I. J.;Marques-Sule E.;Facila-Rubio L.;Perez-Silvestre J.;Garcia-Gonzalez P.;Garcia-Escriva D.;Pellicer-Cabo A.;de laFuente Galan L.;Diaz J. L.;Platero A. R.;Arias J. C.;Blasco-Peiro T.;Julve M. S.;Sanchez-Insa E.;Portoles-Ocampo A.;Melin M.;Hagglund;Lindahl I. -M.;Asserlund B.;Olsson L.;Dahlstrom U.;Afzelius M.;Karlstrom P.;Tengvall L.;Olsson B.;Kalayci S.;Cavusoglu Y.;Gencer E.;Yilmaz M. B.;Gunes H.

2020

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.

Scheda breve

Scheda completa

Scheda completa (DC)

	Parole chiave
	
				Chronic heart failure; Drug titration; Furosemide; Loop diuretics; Mortality; Prognosis; Aged; Diuretics; Female; Hospitalization; Humans; Male; Middle Aged; Registries; Sodium Potassium Chloride Symporter Inhibitors; Stroke Volume; Heart Failure
			
	Settori scientifico-disciplinari dell'articolo (sola visualizzazione)
	
				Settore MED/11 - Malattie dell'Apparato Cardiovascolare
			
	Data di pubblicazione
	
				giu-2020
			
	Data ahead of print o data di stampa
	
				1-apr-2020
			
	Rivista in ANCE
	
				EUROPEAN JOURNAL OF HEART FAILURE
			
	DOI
	
				https://dx.doi.org/10.1002/ejhf.1796
			
	Tipologia
	
				Article (author)
			
	Appare nelle tipologie:
	
				01 - Articolo su periodico

File in questo prodotto:

File	Dimensione	Formato
European J of Heart Fail - 2020 - Kapelios - Association between loop diuretic dose changes and outcomes in chronic heart (1).pdf accesso riservato Tipologia: Publisher's version/PDF Dimensione 3.57 MB Formato Adobe PDF Visualizza/Apri Richiedi una copia	3.57 MB	Adobe PDF	Visualizza/Apri Richiedi una copia

Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/898158

Citazioni

11

60

56

ND

IRIS Institutional Research Information System - AIR Archivio Istituzionale della Ricerca