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.
| Original language | English |
|---|---|
| Pages (from-to) | 1424-1437 |
| Number of pages | 14 |
| Journal | European Journal of Heart Failure |
| Volume | 22 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 1 Aug 2020 |
Keywords
- Chronic heart failure
- Drug titration
- Furosemide
- Loop diuretics
- Mortality
- Prognosis
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In: European Journal of Heart Failure, Vol. 22, No. 8, 01.08.2020, p. 1424-1437.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Association between loop diuretic dose changes and outcomes in chronic heart failure
T2 - observations from the ESC-EORP Heart Failure Long-Term Registry
AU - Kapelios, Chris J.
AU - Laroche, Cécile
AU - Crespo-Leiro, Maria G.
AU - Anker, Stefan D.
AU - Coats, Andrew J.S.
AU - Díaz-Molina, Beatria
AU - Filippatos, Gerasimos S.
AU - Lainscak, Mitja
AU - Maggioni, Aldo P.
AU - McDonagh, Theresa
AU - Mebazaa, Alexandre
AU - Metra, Marco
AU - Moura, Brenda
AU - Mullens, Wilfried
AU - Piepoli, Massimo F.
AU - Rosano, Giuseppe M.C.
AU - Ruschitzka, Frank
AU - Seferovic, Petar M.
AU - Lund, Lars H.
AU - Gale, Christopher Peter
AU - Beleslin, Branko
AU - Budaj, Andrzej
AU - Chioncel, Ovidiu
AU - Dagres, Nikolaos
AU - Danchin, Nicolas
AU - Erlinge, David
AU - Emberson, Jonathan
AU - Glikson, Michael
AU - Gray, Alastair
AU - Kayikcioglu, Meral
AU - Nagy, Klaudia Vivien
AU - Nedoshivin, Aleksandr
AU - Petronio, Anna Sonia
AU - Roos-Hesselink, Jolien
AU - Wallentin, Lars
AU - Zeymer, Uwe
AU - Ferrari, R.
AU - Goda, A.
AU - Diez, M.
AU - Fernandez, A.
AU - Fruhwald, F.
AU - Gatzov, P.
AU - Kurlianskaya, A.
AU - Hullin, R.
AU - Christodoulides, T.
AU - Hradec, J.
AU - Nielsen, O. Wendelboe
AU - Nedjar, R.
AU - Uuetoa, T.
AU - Jimenez, J. F.Delgado
AU - Harjola, V. P.
AU - Logeart, D.
AU - Tousoulis, D.
AU - Milicic, D.
AU - Merkely, B.
AU - Amir, O.
AU - Shotan, A.
AU - Shafie, D.
AU - Mirrakhimov, E.
AU - Kavoliuniene, A.
AU - Erglis, A.
AU - Otljanska, M.
AU - Kostovska, E. Srbinovska
AU - DeMarco, D. Cassar
AU - Drozdz, J.
AU - Fonseca, C.
AU - Dekleva, M.
AU - Dahlstrom, U.
AU - Goncalvesova, E.
AU - Estrago, V.
AU - Bajraktari, G.
AU - Auer, J.
AU - Ablasser, K.
AU - Dolze, T.
AU - Brandner, K.
AU - Gstrein, S.
AU - Poelzl, G.
AU - Moertl, D.
AU - Reiter, S.
AU - Muslibegovic, A.
AU - Vasilj, M.
AU - Fazlibegovic, E.
AU - Cesko, M.
AU - Zelenika, D.
AU - Palic, B.
AU - Pravdic, D.
AU - Cuk, D.
AU - Vitlianova, K.
AU - Katova, T.
AU - Kurteva, T.
AU - Kamenova, D.
AU - Antova, M.
AU - Krejci, J.
AU - Spinar, J.
AU - Krupicka, J.
AU - Malek, F.
AU - Hegarova, M.
AU - Lazarova, M.
AU - Monhart, Z.
AU - Hassanein, M.
AU - El Messiry, F.
AU - El Shazly, A. H.
AU - Elrakshy, Y.
AU - Youssef, A.
AU - Moneim, A. A.
AU - Noamany, M.
AU - Dayem, T. K.Abdel
AU - Farag, N.
AU - Halawa, S. Ibrahim
AU - Hamid, M. Abdel
AU - Saleh, A.
AU - Ebeid, H.
AU - Hanna, R.
AU - Louis, O.
AU - Enen, M. A.
AU - Ibrahim, B. S.
AU - Nasr, G.
AU - Elbahry, A.
AU - Sobhy, H.
AU - Ashmawy, M.
AU - Gouda, M.
AU - Aboleineen, W.
AU - Bernard, Y.
AU - Meneveau, N.
AU - Pillot, M.
AU - Morel, M.
AU - Seronde, M. F.
AU - Schiele, F.
AU - Briand, F.
AU - Delahaye, F.
AU - Damy, T.
AU - Eicher, J. C.
AU - de Groote, P.
AU - Fertin, M.
AU - Lamblin, N.
AU - Isnard, R.
AU - Thevenin, S.
AU - Hagege, A.
AU - Le Marcis, V.
AU - Ly, J. F.
AU - Coisne, D.
AU - Lequeux, B.
AU - Le Moal, V.
AU - Mascle, S.
AU - Lotton, P.
AU - Behar, N.
AU - Donal, E.
AU - Ridard, C.
AU - Reynaud, A.
AU - Basquin, A.
AU - Bauer, F.
AU - Codjia, R.
AU - Galinier, M.
AU - Tourikis, P.
AU - Stavroula, M.
AU - Stefanadis, C.
AU - Chrysohoou, C.
AU - Kotrogiannis, I.
AU - Matzaraki, V.
AU - Karavidas, A.
AU - Tsitsinakis, G.
AU - Nanas, J.
AU - Kampouri, H.
AU - Nana, E.
AU - Kaldara, E.
AU - Eugenidou, A.
AU - Vardas, P.
AU - Saloustros, I.
AU - Tsaknakis, T.
AU - Evangelou, S.
AU - Tziourganou, H.
AU - Tsaroucha, A.
AU - Papadopoulou, A.
AU - Douras, A.
AU - Polgar, L.
AU - Kosztin, A.
AU - Nyolczas, N.
AU - Nagy, A. Csaba
AU - Halmosi, R.
AU - Elber, J.
AU - Fuhrmann, A. Vazan
AU - Romano, S.
AU - Marcon, S.
AU - Penco, M.
AU - Di Mauro, M.
AU - Lemme, E.
AU - Carubelli, V.
AU - Rovetta, R.
AU - Bulgari, M.
AU - Quinzani, F.
AU - Bosi, S.
AU - Schiavina, G.
AU - Squeri, A.
AU - Di Tano, G.
AU - Pirelli, S.
AU - Fucili, A.
AU - Passero, T.
AU - Musio, S.
AU - Di Biase, M.
AU - Correale, M.
AU - Salvemini, G.
AU - Brognoli, S.
AU - Zanelli, E.
AU - Giordano, A.
AU - Agostoni, P.
AU - Salvioni, E.
AU - Copelli, S.
AU - Modena, M. G.
AU - Valenti, C.
AU - Olaru, A.
AU - Bandino, S.
AU - Deidda, M.
AU - Mercuro, G.
AU - Marino, P. N.
AU - Di Ruocco, M. V.
AU - Piccinino, C.
AU - Parrinello, G.
AU - Licata, G.
AU - Torres, D.
AU - Giambanco, S.
AU - Busalacchi, S.
AU - Arrotti, S.
AU - Novo, S.
AU - Inciardi, R. M.
AU - Pieri, P.
AU - Galifi, M. Ausilia
AU - Teresi, G.
AU - Buccheri, D.
AU - Minacapelli, A.
AU - Veniani, M.
AU - Frisinghelli, A.
AU - Priori, S. G.
AU - Cattaneo, S.
AU - Opasich, C.
AU - Gualco, A.
AU - Pagliaro, M.
AU - Mancone, M.
AU - Fedele, F.
AU - Cinque, A.
AU - Vellini, M.
AU - Scarfo, I.
AU - Romeo, F.
AU - Ferraiuolo, F.
AU - Sergi, D.
AU - Anselmi, M.
AU - Melandri, F.
AU - Leci, E.
AU - Iori, E.
AU - Bovolo, V.
AU - Frea, S.
AU - Bergerone, S.
AU - Botta, M.
AU - Canavosio, F. G.
AU - Gaita, F.
AU - Merlo, M.
AU - Cinquetti, M.
AU - Sinagra, G.
AU - Ramani, F.
AU - Fabris, E.
AU - Artico, J.
AU - Miani, D.
AU - Fresco, C.
AU - Daneluzzi, C.
AU - Proclemer, A.
AU - Cicoira, M.
AU - Zanolla, L.
AU - Marchese, G.
AU - Torelli, F.
AU - Vassanelli, C.
AU - Voronina, N.
AU - Tamakauskas, V.
AU - Smalinskas, V.
AU - Karaliute, R.
AU - Petraskiene, I.
AU - Rumbinaite, E.
AU - Brazyte-Ramanauskiene, R.
AU - Petraskiene, D.
AU - Sinkiewicz, W.
AU - Gilewski, W.
AU - Pietrzak, J.
AU - Orzel, T.
AU - Kardaszewicz, P.
AU - Lazorko-Piega, M.
AU - Mosakowska, K.
AU - Bellwon, J.
AU - Rynkiewicz, A.
AU - Raczak, G.
AU - Lewicka, E.
AU - Dabrowska-Kugacka, A.
AU - Bartkowiak, R.
AU - Wozakowska-Kaplon, B.
AU - Krzeminski, A.
AU - Zabojszcz, M.
AU - Grzegorzko, A.
AU - Bury, K.
AU - Nessler, J.
AU - Zalewski, J.
AU - Furman, A.
AU - Poliwczak, A.
AU - Bala, A.
AU - Zycinski, P.
AU - Rudzinska, M.
AU - Jankowski, L.
AU - Kasprzak, J. D.
AU - Michalak, L.
AU - Soska, K. Wojtczak
AU - Huziuk, I.
AU - Flis, P.
AU - Weglarz, J.
AU - Bodys, A.
AU - Grajek, S.
AU - Straburzynska-Migaj, E.
AU - Dankowski, R.
AU - Szymanowska, K.
AU - Szyszka, A.
AU - Nowicka, A.
AU - Samcik, M.
AU - Wolniewicz, L.
AU - Komorowska, K.
AU - Poprawa, I.
AU - Komorowska, E.
AU - Sajnaga, D.
AU - Zolbach, A.
AU - Abdulkarim, A. F.
AU - Lauko-Rachocka, A.
AU - Kaminski, L.
AU - Kostka, A.
AU - Cichy, A.
AU - Ruszkowski, P.
AU - Splawski, M.
AU - Fitas, G.
AU - Szymczyk, A.
AU - Serwicka, A.
AU - Fiega, A.
AU - Zysko, D.
AU - Krysiak, W.
AU - Szabowski, S.
AU - Skorek, E.
AU - Pruszczyk, P.
AU - Bienias, P.
AU - Ciurzynski, M.
AU - Welnicki, M.
AU - Mamcarz, A.
AU - Folga, A.
AU - Zielinski, T.
AU - Rywik, T.
AU - Leszek, P.
AU - Sobieszczanska-Malek, M.
AU - Kozar-Kaminska, K.
AU - Komuda, K.
AU - Wisniewska, J.
AU - Tarnowska, A.
AU - Marchel, M.
AU - Opolski, G.
AU - Kaplon-Cieslicka, A.
AU - Gil, R. J.
AU - Mozenska, O.
AU - Gil, K.
AU - Pawlak, A.
AU - Michalek, A.
AU - Krzesinski, P.
AU - Piotrowicz, K.
AU - Stanczyk, A.
AU - Skrobowski, A.
AU - Ponikowski, P.
AU - Jankowska, E.
AU - Rozentryt, P.
AU - Polonski, L.
AU - Nowalany-Kozielska, E.
AU - Kuczaj, A.
AU - Kalarus, Z.
AU - Szulik, M.
AU - Klys, J.
AU - Prokop-Lewicka, G.
AU - Kleinrok, A.
AU - TavaresAguiar, C.
AU - Ventosa, A.
AU - Pereira, S.
AU - Faria, R.
AU - Chin, J.
AU - DeJesus, I.
AU - Santos, R.
AU - Silva, P.
AU - Moreno, N.
AU - Lourenço, C.
AU - Pereira, A.
AU - Castro, A.
AU - Andrade, A.
AU - OliveiraGuimaraes, T.
AU - Martins, S.
AU - Placido, R.
AU - Lima, G.
AU - Brito, D.
AU - Francisco, A. R.
AU - Proenca, M.
AU - Araujo, I.
AU - Marques, F.
AU - Campelo, M.
AU - Silva-Cardoso, J.
AU - Rodrigues, J.
AU - Rangel, I.
AU - Martins, E.
AU - Peres, M.
AU - Marta, L.
AU - Severino, D.
AU - Durao, D.
AU - Leao, S.
AU - Magalhaes, P.
AU - Moreira, I.
AU - Ferreira, C.
AU - Araujo, C.
AU - Ferreira, A.
AU - Baptista, A.
AU - Radoi, M.
AU - Bicescu, G.
AU - Vinereanu, D.
AU - Sinescu, C. J.
AU - Macarie, C.
AU - Popescu, R.
AU - Daha, I.
AU - Dan, G. A.
AU - Stanescu, C.
AU - Dan, A.
AU - Craiu, E.
AU - Nechita, E.
AU - Christodorescu, R.
AU - Otasevic, P.
AU - Simeunovic, D.
AU - Ristic, A. D.
AU - Celic, V.
AU - Pavlovic-Kleut, M.
AU - Stojcevski, B.
AU - Pencic, B.
AU - Stevanovic, A.
AU - Andric, A.
AU - Simić, Dragan
AU - Ašanin, Milika
AU - Iric-Cupic, V.
AU - Jovic, M.
AU - Milanov, S.
AU - Mitic, V.
AU - Atanaskovic, V.
AU - Antic, S.
AU - Pavlovic, M.
AU - Stanojevic, D.
AU - Stoickov, V.
AU - Ilic, S.
AU - DeljaninIlic, M.
AU - Petrovic, D.
AU - Stojsic, S.
AU - Kecojevic, S.
AU - Dodic, S.
AU - Adic, N. Cemerlic
AU - Cankovic, M.
AU - Stojiljkovic, J.
AU - Mihajlovic, B.
AU - Radin, A.
AU - Radovanovic, S.
AU - Krotin, M.
AU - Klabnik, A.
AU - Pernicky, M.
AU - Murin, J.
AU - Kovar, F.
AU - Kmec, J.
AU - Strasek, M.
AU - Iskra, M. Savnik
AU - Ravnikar, T.
AU - Suligoj, N. Cernic
AU - Fras, Z.
AU - Jug, B.
AU - Glavic, T.
AU - Losic, R.
AU - Bombek, M.
AU - Krunic, B.
AU - Horvat, S.
AU - Kovac, D.
AU - Rajtman, D.
AU - Letonja, M.
AU - Winkler, R.
AU - Melihen-Bartolic, C.
AU - Bartolic, A.
AU - Kladnik, M.
AU - Pusnik, C. Slemenik
AU - Marolt, A.
AU - Klen, J.
AU - Drnovsek, B.
AU - Leskovar, B.
AU - Anguita, M. J.Fernandez
AU - GallegoPage, J. C.
AU - Martinez, F. M.Salmeron
AU - Andres, J.
AU - Bayes-Genis, A.
AU - Mirabet, S.
AU - Mendez, A.
AU - Garcia-Cosio, L.
AU - Leon, V.
AU - Gonzalez-Costello, J.
AU - Muntane, G.
AU - Garay, A.
AU - Alcade-Martinez, V.
AU - Fernandez, S. Lopez
AU - Rivera-Lopez, R.
AU - Fernandez-Alvarez, M.
AU - Serrano-Martinez, J. L.
AU - Grille-Cancela, Z.
AU - Marzoa-Rivas, R.
AU - Paniagua-Martin, M. J.
AU - Barge-Caballero, E.
AU - Gonzalez-Gallarza, R. Dalmau
AU - SalvadorMontanes, O.
AU - Manjavacas, A. M.Iniesta
AU - Conde, A. Castro
AU - Araujo, A.
AU - Soria, T.
AU - Gomez-Bueno, M.
AU - Cobo-Marcos, M.
AU - Alonso-Pulpon, L.
AU - SegoviaCubero, J.
AU - Sayago, I.
AU - Gonzalez-Segovia, A.
AU - Briceno, A.
AU - Subias, P. Escribano
AU - Cano, M. J.Ruiz
AU - Sanchez, M. A.Gomez
AU - Pinilla, J. M.Garcia
AU - de la Villa, B. Garcia
AU - Sahuquillo, A.
AU - Marques, R. Bravo
AU - Calvo, F. Torres
AU - Perez-Martinez, M. T.
AU - Garrido-Bravo, I. P.
AU - Pastor-Perez, F.
AU - Pascual-Figal, D. A.
AU - Molina, B. Diaz
AU - Orus, J.
AU - Gonzalo, F. Epelde
AU - Bertomeu, V.
AU - Valero, R.
AU - Martinez-Abellan, R.
AU - Quiles, J.
AU - Mateo, I.
AU - ElAmrani, A.
AU - Fernandez-Vivancos, C.
AU - Valero, D. Bierge
AU - Almenar-Bonet, L.
AU - Sanchez-Lazaro, I. J.
AU - Marques-Sule, E.
AU - Facila-Rubio, L.
AU - Perez-Silvestre, J.
AU - Garcia-Gonzalez, P.
AU - Garcia-Escriva, D.
AU - Pellicer-Cabo, A.
AU - de laFuente Galan, L.
AU - Diaz, J. Lopez
AU - Platero, A. Recio
AU - Arias, J. C.
AU - Blasco-Peiro, T.
AU - Julve, M. Sanz
AU - Sanchez-Insa, E.
AU - Portoles-Ocampo, A.
AU - Melin, M.
AU - Hägglund,
AU - Asserlund, B.
AU - Olsson, L.
AU - Lindahl, I. M.
AU - Afzelius, M.
AU - Karlström, P.
AU - Tengvall, L.
AU - Olsson, B.
AU - Kalayci, S.
AU - Cavusoglu, Y.
AU - Gencer, E.
AU - Yilmaz, M. B.
AU - Gunes, H.
N1 - Funding Information: M.G.C.L. reports grants from CIBERCV, grants and personal fees from Novartis, personal fees and non‐financial support from Astellas, Abbott, personal fees from Amgen, non‐financial support from Daichi‐Sankio, outside the submitted work. S.D.A. reports grants and personal fees from Vifor Int, personal fees from Bayer, Boehringer Ingelheim, Novartis, Servier, Impulse Dynamics, SJM, and grants from Abbott Vascular outside the submitted work. A.J.S.C. reports personal fees from AstraZeneca, Bayer, Menarini, Novartis, Nutricia, Servier, Vifor, Actimed, Cardiac Dimensions, CVRx, Enopace, Faraday, Gore, Respicardia, Stealth Peptides, V‐Wave, outside the submitted work. G.F. reports other from Committee Member in trials sponsored by Medtronic, Vifor, Servier, Novartis, BI, outside the submitted work. A.P.M. reports personal fees from Bayer, Fresenius, Novartis, outside the submitted work. A.M. reports personal fees from Novartis, Orion, Roche, Servier, Sanofi, Otsuka, Philips; grants and personal fees from Adrenomed, Abbott; grants from 4TEEN4, outside the submitted work. M.M. reports personal fees from Amgen, Bayer, Fresenius, Servier, Vifor, WindTree as consulting honoraria for participation in executive committees or advisory boards, personal fees from Abbott and Edwards as speaker's bureau, outside the submitted work. B.M. reports personal fees from Boehringer Ingleheim, Novartis; personal fees and non‐financial support from Servier, AstraZeneca, outside the submitted work. F.R. since 1st January 2018: no personal payments/all payments directly to the University of Zurich. Before 2018: he reports grants and personal fees from SJM/Abbott, Servier, Novartis, Bayer; personal fees from Zoll, AstraZeneca, Sanofi, Amgen, BMS, Pfizer, Fresenius, Vifor, Roche, Cardiorentis, Boehringer Ingelheim; other from Heartware; grants from Mars, outside the submitted work. P.M.S. reports Medtronic, Abbott, Servier, AstraZeneca, Respicardia honorarium for lecture, Boehringer Ingelheim and Novartis consultancy agreement and honorarium for lecture. L.H.L. reports personal fees from Merck, Sanofi, Bayer, Pharmacosmos, Abbott, Medscape; grants from Boehringer Ingelheim, Boston Scientific; grants and personal fees from Vifor‐Fresenius, AstraZeneca, Relypsa, Novartis, Mundipharma, outside the submitted work. The other authors have nothing to disclose. Conflict of interest: Funding Information: Since the start of EORP, the following companies have supported the programme: Abbott Vascular Int. (2011–2021), Amgen Cardiovascular (2009–2018), AstraZeneca (2014–2021), Bayer AG (2009–2018), Boehringer Ingelheim (2009–2019), Boston Scientific (2009–2012), The Bristol-Myers Squibb and Pfizer Alliance (2011–2019), Daiichi-Sankyo Europe GmbH (2011–2020), The Alliance Daiichi-Sankyo Europe GmbH and Eli Lilly and Company (2014–2017), Edwards (2016–2019), Gedeon Richter Plc. (2014–2016), Menarini Int. Op. (2009–2012), MSD-Merck & Co. (2011–2014), Novartis Pharma AG (2014–2020), ResMed (2014–2016), Sanofi (2009–2011), Servier (2009–2021), Vifor (2019–2022). Conflict of interest: M.G.C.L. reports grants from CIBERCV, grants and personal fees from Novartis, personal fees and non-financial support from Astellas, Abbott, personal fees from Amgen, non-financial support from Daichi-Sankio, outside the submitted work. S.D.A. reports grants and personal fees from Vifor Int, personal fees from Bayer, Boehringer Ingelheim, Novartis, Servier, Impulse Dynamics, SJM, and grants from Abbott Vascular outside the submitted work. A.J.S.C. reports personal fees from AstraZeneca, Bayer, Menarini, Novartis, Nutricia, Servier, Vifor, Actimed, Cardiac Dimensions, CVRx, Enopace, Faraday, Gore, Respicardia, Stealth Peptides, V-Wave, outside the submitted work. G.F. reports other from Committee Member in trials sponsored by Medtronic, Vifor, Servier, Novartis, BI, outside the submitted work. A.P.M. reports personal fees from Bayer, Fresenius, Novartis, outside the submitted work. A.M. reports personal fees from Novartis, Orion, Roche, Servier, Sanofi, Otsuka, Philips; grants and personal fees from Adrenomed, Abbott; grants from 4TEEN4, outside the submitted work. M.M. reports personal fees from Amgen, Bayer, Fresenius, Servier, Vifor, WindTree as consulting honoraria for participation in executive committees or advisory boards, personal fees from Abbott and Edwards as speaker's bureau, outside the submitted work. B.M. reports personal fees from Boehringer Ingleheim, Novartis; personal fees and non-financial support from Servier, AstraZeneca, outside the submitted work. F.R. since 1st January 2018: no personal payments/all payments directly to the University of Zurich. Before 2018: he reports grants and personal fees from SJM/Abbott, Servier, Novartis, Bayer; personal fees from Zoll, AstraZeneca, Sanofi, Amgen, BMS, Pfizer, Fresenius, Vifor, Roche, Cardiorentis, Boehringer Ingelheim; other from Heartware; grants from Mars, outside the submitted work. P.M.S. reports Medtronic, Abbott, Servier, AstraZeneca, Respicardia honorarium for lecture, Boehringer Ingelheim and Novartis consultancy agreement and honorarium for lecture. L.H.L. reports personal fees from Merck, Sanofi, Bayer, Pharmacosmos, Abbott, Medscape; grants from Boehringer Ingelheim, Boston Scientific; grants and personal fees from Vifor-Fresenius, AstraZeneca, Relypsa, Novartis, Mundipharma, outside the submitted work. The other authors have nothing to disclose. EORP Oversight Committee, Registry Executive and Steering Committees of the EURObservational Research Programme (EORP). Data collection was conducted by the EORP department from the ESC by Emanuela Fiorucci as Project Officer, Gérard Gracia and Maryna Andarala as Data Managers. Statistical analyses were performed by Cécile Laroche. Overall activities were coordinated and supervised by Dr. Aldo P. Maggioni (EORP Scientific Coordinator). Since the start of EORP, the following companies have supported the programme: Abbott Vascular Int. (2011–2021), Amgen Cardiovascular (2009–2018), AstraZeneca (2014–2021), Bayer AG (2009–2018), Boehringer Ingelheim (2009–2019), Boston Scientific (2009–2012), The Bristol-Myers Squibb and Pfizer Alliance (2011–2019), Daiichi-Sankyo Europe GmbH (2011–2020), The Alliance Daiichi-Sankyo Europe GmbH and Eli Lilly and Company (2014–2017), Edwards (2016–2019), Gedeon Richter Plc. (2014–2016), Menarini Int. Op. (2009–2012), MSD-Merck & Co. (2011–2014), Novartis Pharma AG (2014–2020), ResMed (2014–2016), Sanofi (2009–2011), Servier (2009–2021), Vifor (2019–2022). Conflict of interest: M.G.C.L. reports grants from CIBERCV, grants and personal fees from Novartis, personal fees and non-financial support from Astellas, Abbott, personal fees from Amgen, non-financial support from Daichi-Sankio, outside the submitted work. S.D.A. reports grants and personal fees from Vifor Int, personal fees from Bayer, Boehringer Ingelheim, Novartis, Servier, Impulse Dynamics, SJM, and grants from Abbott Vascular outside the submitted work. A.J.S.C. reports personal fees from AstraZeneca, Bayer, Menarini, Novartis, Nutricia, Servier, Vifor, Actimed, Cardiac Dimensions, CVRx, Enopace, Faraday, Gore, Respicardia, Stealth Peptides, V-Wave, outside the submitted work. G.F. reports other from Committee Member in trials sponsored by Medtronic, Vifor, Servier, Novartis, BI, outside the submitted work. A.P.M. reports personal fees from Bayer, Fresenius, Novartis, outside the submitted work. A.M. reports personal fees from Novartis, Orion, Roche, Servier, Sanofi, Otsuka, Philips; grants and personal fees from Adrenomed, Abbott; grants from 4TEEN4, outside the submitted work. M.M. reports personal fees from Amgen, Bayer, Fresenius, Servier, Vifor, WindTree as consulting honoraria for participation in executive committees or advisory boards, personal fees from Abbott and Edwards as speaker's bureau, outside the submitted work. B.M. reports personal fees from Boehringer Ingleheim, Novartis; personal fees and non-financial support from Servier, AstraZeneca, outside the submitted work. F.R. since 1st January 2018: no personal payments/all payments directly to the University of Zurich. Before 2018: he reports grants and personal fees from SJM/Abbott, Servier, Novartis, Bayer; personal fees from Zoll, AstraZeneca, Sanofi, Amgen, BMS, Pfizer, Fresenius, Vifor, Roche, Cardiorentis, Boehringer Ingelheim; other from Heartware; grants from Mars, outside the submitted work. P.M.S. reports Medtronic, Abbott, Servier, AstraZeneca, Respicardia honorarium for lecture, Boehringer Ingelheim and Novartis consultancy agreement and honorarium for lecture. L.H.L. reports personal fees from Merck, Sanofi, Bayer, Pharmacosmos, Abbott, Medscape; grants from Boehringer Ingelheim, Boston Scientific; grants and personal fees from Vifor-Fresenius, AstraZeneca, Relypsa, Novartis, Mundipharma, outside the submitted work. The other authors have nothing to disclose. Publisher Copyright: © 2020 European Society of Cardiology
PY - 2020/8/1
Y1 - 2020/8/1
N2 - 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.
AB - 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.
KW - Chronic heart failure
KW - Drug titration
KW - Furosemide
KW - Loop diuretics
KW - Mortality
KW - Prognosis
UR - http://www.scopus.com/inward/record.url?scp=85082578888&partnerID=8YFLogxK
U2 - 10.1002/ejhf.1796
DO - 10.1002/ejhf.1796
M3 - Article
C2 - 32237110
AN - SCOPUS:85082578888
SN - 1388-9842
VL - 22
SP - 1424
EP - 1437
JO - European Journal of Heart Failure
JF - European Journal of Heart Failure
IS - 8
ER -