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

Chris J Kapelios; Cécile Laroche; Maria G Crespo-Leiro; Stefan D Anker; Andrew J S Coats; Beatria Díaz-Molina; Gerasimos Filippatos; Mitja Lainscak; Aldo P Maggioni; Theresa McDonagh; Alexandre Mebazaa; Marco Metra; Brenda Moura; Wilfried Mullens; Massimo F Piepoli; Giuseppe M C Rosano; Frank Ruschitzka; Petar M Seferovic; Lars H Lund; Heart Failure Long-Term Registry Investigators Group

doi: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

Eur J Heart Fail. 2020 Aug;22(8):1424-1437. doi: 10.1002/ejhf.1796. Epub 2020 Apr 1.

Authors

Chris J Kapelios¹, Cécile Laroche², Maria G Crespo-Leiro³, Stefan D Anker⁴, Andrew J S Coats⁵, Beatria Díaz-Molina⁶, Gerasimos Filippatos⁷, Mitja Lainscak⁸, Aldo P Maggioni^{2

9}, Theresa McDonagh¹⁰, Alexandre Mebazaa¹¹, Marco Metra¹², Brenda Moura¹³, Wilfried Mullens¹⁴, Massimo F Piepoli¹⁵, Giuseppe M C Rosano⁵, Frank Ruschitzka¹⁶, Petar M Seferovic¹⁷, Lars H Lund¹⁸; Heart Failure Long-Term Registry Investigators Group

Collaborators

Heart Failure Long-Term Registry Investigators Group:
Christopher Peter Gale, Branko Beleslin, Andrzej Budaj, Ovidiu Chioncel, Nikolaos Dagres, Nicolas Danchin, David Erlinge, Jonathan Emberson, Michael Glikson, Alastair Gray, Meral Kayikcioglu, Aldo Maggioni, Klaudia Vivien Nagy, Aleksandr Nedoshivin, Anna-Sonia Petronio, Jolien Roos-Hesselink, Lars Wallentin, Uwe Zeymer, M Crespo-Leiro, S Anker, A Mebazaa, A Coats, G Filippatos, R Ferrari, A P Maggioni, M F Piepoli, A Goda, M Diez, A Fernandez, F Fruhwald, P Gatzov, A Kurlianskaya, R Hullin, T Christodoulides, J Hradec, O Wendelboe Nielsen, R Nedjar, T Uuetoa, J F Delgado Jimenez, V-P Harjola, D Logeart, D Tousoulis, D Milicic, B Merkely, O Amir, A Shotan, D Shafie, M Metra, E Mirrakhimov, A Kavoliuniene, A Erglis, M Otljanska, E Srbinovska Kostovska, D Cassar 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 Abdel Dayem, N Farag, S Ibrahim Halawa, M Abdel 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-F Seronde, F Schiele, F Briand, F Delahaye, T Damy, J-C Eicher, P de Groote, M Fertin, N Lamblin, R Isnard, S Thevenin, A Hagege, D Logeart, V Le Marcis, J-F 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 Csaba Nagy, R Halmosi, J Elber, A Shotan, A Vazan Fuhrmann, O Amir, S Romano, S Marcon, M Penco, M Di Mauro, E Lemme, V Carubelli, R Rovetta, M Metra, 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 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 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 Wojtczak 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-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, 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 Lourenço, 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-J Sinescu, C Macarie, R Popescu, I Daha, G-A 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, Dragan Simić, Milika Ašanin, 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 Cemerlic 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 Savnik Iskra, T Ravnikar, N Cernic 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 Slemenik Pusnik, A Marolt, J Klen, B Drnovsek, B Leskovar, M J Fernandez Anguita, J C GallegoPage, F M Salmeron 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 Lopez Fernandez, R Rivera-Lopez, M Fernandez-Alvarez, J L Serrano-Martinez, M Crespo-Leiro, Z Grille-Cancela, R Marzoa-Rivas, M J Paniagua-Martin, E Barge-Caballero, R Dalmau Gonzalez-Gallarza, O SalvadorMontanes, A M Iniesta Manjavacas, A Castro Conde, A Araujo, T Soria, M Gomez-Bueno, M Cobo-Marcos, L Alonso-Pulpon, J SegoviaCubero, I Sayago, A Gonzalez-Segovia, A Briceno, P Escribano Subias, M J Ruiz Cano, M A Gomez Sanchez, J F Delgado Jimenez, J M Garcia Pinilla, B Garcia de la Villa, A Sahuquillo, R Bravo Marques, F Torres Calvo, M T Perez-Martinez, 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, 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, D Garcia-Escriva, A Pellicer-Cabo, L de laFuente Galan, J Lopez Diaz, A Recio Platero, J C Arias, T Blasco-Peiro, M Sanz Julve, E Sanchez-Insa, A Portoles-Ocampo, M Melin, Hägglund, A Stenberg, I-M Lindahl, B Asserlund, L Olsson, U Dahlström, M Afzelius, P Karlström, L Tengvall, B Olsson, S Kalayci, Y Cavusoglu, E Gencer, M B Yilmaz, H Gunes

Affiliations

¹ Department of Cardiology, Laiko General Hospital, Athens, Greece.
² EURObservational Research Programme, European Society of Cardiology, Sophia-Antipolis, France.
³ Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco, Complexo Hospitalario Universitario A Coruna, CHUAC, INIBIC, UDC, CIBERCV, La Coruna, Spain.
⁴ Department of Cardiology (CVK), Berlin Institute of Health Center for Regenerative Therapies (BCRT); German Centre for Cardiovascular Research (DZHK) Partner Site Berlin; Charité Universitätsmedizin Berlin, Berlin, Germany.
⁵ IRCCS, San Raffaele Pisana, Rome, Italy.
⁶ Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco, Hospital Universitario Central de Asturias, Oviedo, Spain.
⁷ Department of Cardiology, School of Medicine, University of Cyprus & Heart Failure Unit, University Hospital Attikon, National and Kapodistrian Univeristy of Athens, Athens, Greece.
⁸ Division of Cardiology, Murska Sobota, Murska Sobota and Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
⁹ ANMCO Research Center, Florence, Italy.
¹⁰ King's College Hospital, London, UK.
¹¹ Department of Anesthesia-Burn-Critical Care, UMR 942 Inserm - MASCOT, University of Paris; APHP Saint Louis Lariboisière University Hospitals, Paris, France.
¹² Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy.
¹³ Department of Cardiology, Hospital Militar, Porto, Cintesis- Faculty of Medicine, University of Porto, Porto, Portugal.
¹⁴ Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium; Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium.
¹⁵ Heart Failure Unit, Cardiac Department, G. da Saliceto Hospital, AUSL, Piacenza, Italy.
¹⁶ Clinic of Cardiology, University Hospital, Zürich, Switzerland.
¹⁷ University of Belgrade Faculty of Medicine, Belgrade, Serbia.
¹⁸ Unit of Cardiology, Department of Medicine, Karolinska Institutet, and Heart and Vascular Theme, Karolinska University Hospital, Stockholm, Sweden.

PMID: 32237110
DOI: 10.1002/ejhf.1796

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.

Keywords: Chronic heart failure; Drug titration; Furosemide; Loop diuretics; Mortality; Prognosis.

MeSH terms

Aged
Diuretics
Female
Heart Failure* / drug therapy
Heart Failure* / epidemiology
Hospitalization
Humans
Male
Middle Aged
Registries
Sodium Potassium Chloride Symporter Inhibitors
Stroke Volume

Substances

Diuretics
Sodium Potassium Chloride Symporter Inhibitors