Patrick Rossignol1, Mitja Lainscak2, Maria G Crespo-Leiro3, Cécile Laroche4, Massimo F Piepoli5, Gerasimos Filippatos6, Giuseppe M C Rosano7, Gianluigi Savarese8, Stefan D Anker9, Petar M Seferovic10, Frank Ruschitzka11, Andrew J S Coats7, Alexandre Mebazaa12, Theresa McDonagh13, Ana Sahuquillo14, Maria Penco15, Aldo P Maggioni4,16, Lars H Lund17. 1. Université de Lorraine, Centre d'Investigation Clinique Plurithématique 1433-INSERM-CHRU de Nancy, Inserm U1116 & FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France. 2. Division of Cardiology, General Hospital Murska Sobota, Murska Sobota and Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. 3. Unidad de Insuficiencia Cardiaca y Trasplante Cardiaco, Complexo Hospitalario Universitario A Coruna (CHUAC), INIBIC, UDC, CIBERCV, La Coruna, Spain. 4. EURObservational Research Programme, European Society of Cardiology, Sophia-Antipolis, France. 5. Heart Failure Unit, Cardiac Department, G. da Saliceto Hospital, AUSL Piacenza, Italy. 6. School of Medicine, University of Cyprus & Heart Failure Unit, Department of Cardiology, University Hospital Attikon, National and Kapodistrian University of Athens, Athens, Greece. 7. IRCCS San Raffaele Pisana, Rome, Italy. 8. Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Heart and Vascular Theme, Karolinska University Hospital, Stockholm, Sweden. 9. Department of Cardiology (CVK), and Berlin Institute of Health Center for Regenerative Therapies (BCRT); German Centre for Cardiovascular Research (DZHK) partner site Berlin, Charité Universitätsmedizin, Berlin, Germany. 10. University of Belgrade Faculty of Medicine, Belgrade, Serbia. 11. University Hospital, Clinic of Cardiology, Zurich, Switzerland. 12. UMR 942 Inserm MASCOT, Université de Paris; APHP Saint Louis Lariboisière University Hospitals, Department of Anesthesia-Burn-Critical Care, and FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Paris, France. 13. King's College Hospital, London, UK. 14. Hospital de Manacor, Balearic Island, Spain. 15. Cardiology University of L'Aquila, L'Aquila, Italy. 16. ANMCO Research Center, Florence, Italy. 17. Unit of Cardiology, Department of Medicine, Karolinska Institutet, and Heart and Vascular Theme, Karolinska University Hospital, Stockholm, Sweden.
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.
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.
Authors: Daniela Tomasoni; Julie K K Vishram-Nielsen; Matteo Pagnesi; Marianna Adamo; Carlo Mario Lombardi; Finn Gustafsson; Marco Metra Journal: ESC Heart Fail Date: 2022-03-30
Authors: João Pedro Ferreira; Ulrik M Mogensen; Pardeep S Jhund; Akshay S Desai; Jean-Lucien Rouleau; Michael R Zile; Patrick Rossignol; Faiez Zannad; Milton Packer; Scott D Solomon; John J V McMurray Journal: Eur J Heart Fail Date: 2020-09-29 Impact factor: 15.534
Authors: Adriaan A Voors; Hillary Mulder; Eugene Reyes; Martin R Cowie; Johan Lassus; Adrian F Hernandez; Justin A Ezekowitz; Javed Butler; Christopher M O'Connor; Joerg Koglin; Carolyn S P Lam; Burkert Pieske; Lothar Roessig; Piotr Ponikowski; Kevin J Anstrom; Paul W Armstrong Journal: Eur J Heart Fail Date: 2021-06-03 Impact factor: 15.534