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.
| Original language | English |
|---|---|
| Pages (from-to) | 1378-1389 |
| Number of pages | 12 |
| Journal | European Journal of Heart Failure |
| Volume | 22 |
| Issue number | 8 |
| DOIs | |
| State | Published - 1 Aug 2020 |
Bibliographical note
Publisher Copyright:© 2020 European Society of Cardiology
Funding
P.R. reports grants and personal fees from AstraZeneca, Bayer, CVRx, Novartis, personal fees from Fresenius, Grunenthal, Servier, Stealth Peptides, Vifor Fresenius Medical Care Renal Pharma, Idorsia, NovoNordisk, Ablative Solutions, G3P, Corvidia, Relypsa, outside the submitted work; and Cofounder: CardioRenal, a company developing a telemonitoring loop in heart failure (including potassium measurements). M.L. reports personal fees from Vifor, AstraZeneca during the conduct of the study; grants from Roche, Boehringer Ingelheim, personal fees from Novartis, outside the submitted work. M.G.C.L. reports grants from CIBERCV, personal fees and non‐financial support from Novartis, MSD, personal fees from Abbott, non‐financial support from Daiichi‐Sankyo, Vifor Pharma, grants from AstraZeneca, outside the submitted work. G.F. reports other from Novartis, Servier, BI, Medtronic, Vifor, outside the submitted work. G.S. reports grants and personal fees from Vifor, AstraZeneca, grants and non‐financial support from Boehringer Ingelheim, personal fees from Società Prodotti Antibiotici, Roche, Servier, GENESIS, grants from MSD, Novartis, outside the submitted work. S.D.A. reports grants and personal fees from Vifor Int, Abbott Vascular, personal fees from Bayer, Boehringer Ingelheim, Novartis, Servier, Impulse Dynamics, SJM, outside the submitted work. A.J.S.C. reports personal fees from AstraZeneca, Bayer, Menarini, Novartis, Nutricia, Servier, Vifor, Actimed, Cardiac Dimension, CVRx, Enopace, Faraday, Gore, Respicardia, Stealth Peptides, V‐Wave, outside the submitted work. A.S. reports personal fees from Servier during the conduct of the study. A.P.M. reports personal fees from Bayer, Fresenius, Novartis outside the submitted work. 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: 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 (2009–2018), Vifor (2019–2022). Conflict of interest: P.R. reports grants and personal fees from AstraZeneca, Bayer, CVRx, Novartis, personal fees from Fresenius, Grunenthal, Servier, Stealth Peptides, Vifor Fresenius Medical Care Renal Pharma, Idorsia, NovoNordisk, Ablative Solutions, G3P, Corvidia, Relypsa, outside the submitted work; and Cofounder: CardioRenal, a company developing a telemonitoring loop in heart failure (including potassium measurements). M.L. reports personal fees from Vifor, AstraZeneca during the conduct of the study; grants from Roche, Boehringer Ingelheim, personal fees from Novartis, outside the submitted work. M.G.C.L. reports grants from CIBERCV, personal fees and non-financial support from Novartis, MSD, personal fees from Abbott, non-financial support from Daiichi-Sankyo, Vifor Pharma, grants from AstraZeneca, outside the submitted work. G.F. reports other from Novartis, Servier, BI, Medtronic, Vifor, outside the submitted work. G.S. reports grants and personal fees from Vifor, AstraZeneca, grants and non-financial support from Boehringer Ingelheim, personal fees from Società Prodotti Antibiotici, Roche, Servier, GENESIS, grants from MSD, Novartis, outside the submitted work. S.D.A. reports grants and personal fees from Vifor Int, Abbott Vascular, personal fees from Bayer, Boehringer Ingelheim, Novartis, Servier, Impulse Dynamics, SJM, outside the submitted work. A.J.S.C. reports personal fees from AstraZeneca, Bayer, Menarini, Novartis, Nutricia, Servier, Vifor, Actimed, Cardiac Dimension, CVRx, Enopace, Faraday, Gore, Respicardia, Stealth Peptides, V-Wave, outside the submitted work. A.S. reports personal fees from Servier during the conduct of the study. A.P.M. reports personal fees from Bayer, Fresenius, Novartis outside the submitted work. 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 Committee and Steering Committee 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). All investigators listed in the Supplemental Appendix S1. 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 (2009–2018), Vifor (2019–2022). Conflict of interest: P.R. reports grants and personal fees from AstraZeneca, Bayer, CVRx, Novartis, personal fees from Fresenius, Grunenthal, Servier, Stealth Peptides, Vifor Fresenius Medical Care Renal Pharma, Idorsia, NovoNordisk, Ablative Solutions, G3P, Corvidia, Relypsa, outside the submitted work; and Cofounder: CardioRenal, a company developing a telemonitoring loop in heart failure (including potassium measurements). M.L. reports personal fees from Vifor, AstraZeneca during the conduct of the study; grants from Roche, Boehringer Ingelheim, personal fees from Novartis, outside the submitted work. M.G.C.L. reports grants from CIBERCV, personal fees and non-financial support from Novartis, MSD, personal fees from Abbott, non-financial support from Daiichi-Sankyo, Vifor Pharma, grants from AstraZeneca, outside the submitted work. G.F. reports other from Novartis, Servier, BI, Medtronic, Vifor, outside the submitted work. G.S. reports grants and personal fees from Vifor, AstraZeneca, grants and non-financial support from Boehringer Ingelheim, personal fees from Società Prodotti Antibiotici, Roche, Servier, GENESIS, grants from MSD, Novartis, outside the submitted work. S.D.A. reports grants and personal fees from Vifor Int, Abbott Vascular, personal fees from Bayer, Boehringer Ingelheim, Novartis, Servier, Impulse Dynamics, SJM, outside the submitted work. A.J.S.C. reports personal fees from AstraZeneca, Bayer, Menarini, Novartis, Nutricia, Servier, Vifor, Actimed, Cardiac Dimension, CVRx, Enopace, Faraday, Gore, Respicardia, Stealth Peptides, V-Wave, outside the submitted work. A.S. reports personal fees from Servier during the conduct of the study. A.P.M. reports personal fees from Bayer, Fresenius, Novartis outside the submitted work. 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.
| Funders |
|---|
| Ablative Solutions |
| Alliance Daiichi-Sankyo Europe GmbH |
| GENESIS |
| Gedeon Richter Plc. |
| MSD-Merck & Co. |
| Menarini Int |
| Pfizer Alliance |
| Abbott Laboratories |
| Bristol-Myers Squibb |
| Eli Lilly and Company |
| AstraZeneca |
| Bayer |
| Novartis |
| Roche |
| Meso Scale Diagnostics |
| Boehringer Ingelheim |
| Boston Scientific Corporation |
| European Society of Cardiology |
| Novo Nordisk |
| Vifor Pharma |
| Servier |
| Daiichi Sankyo Europe |
Keywords
- Heart failure
- Hyperkalaemia
- Hypokalaemia
- Mineralocorticoid receptor antagonists
- Prognosis
- Renin–angiotensin–aldosterone system inhibitors
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