Potassium and the use of renin–angiotensin–aldosterone system inhibitors in heart failure with reduced ejection fraction: data from BIOSTAT‐CHF

Beusekamp, Joost C.; Tromp, Jasper; Wal, Haye H. van der; Anker, Stefan D.; Cleland, John G.F.; Dickstein, Kenneth; Filippatos, Gerasimos; Harst, Pim van der; Hillege, Hans L.; Lang, Chim C.; Metra, Marco; Ng, Leong L.; Ponikowski, Piotr; Samani, Nilesh J.; Veldhuisen, Dirk J. van; Zwinderman, Aeilko H.; Rossignol, Patrick; Zannad, Faı̈ez; Voors, Adriaan A.; Meer, Peter van der

doi:10.1002/ejhf.1079

Cited by 60 publications

(80 citation statements)

References 31 publications

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“…More cautious MRA use is required in patients with high serum potassium levels, even when renal function is not significantly reduced, but this issue could be resolved with the use of potassium binders . High serum potassium can also be the reason for a reluctance to up‐titrate ACEIs/ARBs to optimal doses, but it does not adversely impact on the beneficial effects of ACEIs/ARBs . In addition, frailty has been identified as an obstacle to the use of GDMT, in particular MRAs, although their beneficial effects on outcomes appears to be unaffected by frailty .…”

Section: Discussionmentioning

confidence: 99%

“…46 High serum potassium can also be the reason for a reluctance to up-titrate ACEIs/ARBs to optimal doses, but it does not adversely impact on the beneficial effects of ACEIs/ARBs. 47 In addition, frailty has been identified as an obstacle to the use of GDMT, in particular MRAs, although their beneficial effects on outcomes appears to be unaffected by frailty. 48,49 Therefore, GDMT underuse cannot be justified by these clinical scenarios.…”

Section: Baseline and Follow-up Medical Managementmentioning

confidence: 99%

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Sex‐ and age‐related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long‐Term Registry

Lainščak

Milinković

Polovina

et al. 2019

European J of Heart Fail

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AimsThis study aimed to assess age-and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients.Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P ≤ 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P = 0.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P < 0.001) and there were no differences in causes of death. All-cause mortality and all-cause hospitalization increased with greater age in both sexes. Sex was not an independent predictor of 1-year all-cause mortality (restricted to patients with LVEF ≤45%). Mortality risk was significantly lower in patients of younger age, compared to patients aged >75 years.

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Section: Discussionmentioning

confidence: 99%

Section: Baseline and Follow-up Medical Managementmentioning

confidence: 99%

Sex‐ and age‐related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long‐Term Registry

Lainščak

Milinković

Polovina

et al. 2019

European J of Heart Fail

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“…The present study was restricted to an analysis of RAASi discontinuation; however, like recent literature relating serum potassium to RAASi dosing in HF patients, 25 our future work will seek to investigate associations between serum potassium, RAASi down-titration, and adverse outcomes among those in UK clinical practice. Adjusted IRRs presented in this study relate to RAASi discontinuation rates estimated among all patients and intervals observed during the study period, including those patients and intervals where RAASi therapy had not been prescribed.…”

mentioning

confidence: 99%

“…When alternative definitions of RAASi exposure were investigated, the relationship between elevated serum potassium level and increased likelihood of RAASi discontinuation persisted. The present study was restricted to an analysis of RAASi discontinuation; however, like recent literature relating serum potassium to RAASi dosing in HF patients, 25 our future work will seek to investigate associations between serum potassium, RAASi down-titration, and adverse outcomes among those in UK clinical practice.…”

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confidence: 99%

Serum potassium and clinical outcomes in heart failure patients: results of risk calculations in 21 334 patients in the UK

et al. 2019

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Aims At present, the clinical burden of hypokalaemia and hyperkalaemia among European heart failure patients, and relationships between serum potassium and adverse clinical outcomes in this population, is not well characterized. The aim of this study was to investigate associations between mortality, major adverse cardiac events, and renin–angiotensin–aldosterone system inhibitor (RAASi) discontinuation across serum potassium levels, in a UK cohort of incident heart failure patients. Methods and results This was a retrospective observational cohort study of newly diagnosed heart failure patients listed in the Clinical Practice Research Datalink, with a first record of heart failure (index date) between 2006 and 2015. Hypokalaemia and hyperkalaemia episodes were defined as the number of serum potassium measurements exceeding each threshold (<3.5, ≥5.0, ≥5.5, and ≥6.0 mmol/L), without such a measurement in the preceding 7 days. Risk equations developed using Poisson generalized estimating equations were utilized to estimate adjusted incident rate ratios (IRRs) relating serum potassium and clinical outcomes (death, major adverse cardiac event, and RAASi discontinuation). Among 21,334 eligible heart failure patients, 1969 (9.2%), 7648 (35.9%), 2725 (12.8%), and 763 (3.6%) experienced episodes of serum potassium <3.5, ≥5.0, ≥5.5, and ≥6.0 mmol/L, respectively. The adjusted IRRs for mortality exhibited a U‐shaped association pattern with serum potassium. Relative to the reference category (4.5 to <5.0 mmol/L), adjusted IRRs for mortality were estimated as 1.98 (95% confidence interval: 1.69–2.33), 1.23 (1.12–1.36), 1.35 (1.14–1.60), and 3.02 (2.28–4.02), for patients with serum potassium <3.5, ≥5.0 to <5.5, ≥5.5 to <6.0, and ≥6.0 mmol/L, respectively. The adjusted IRRs for major adverse cardiac events demonstrated a non‐statistically significant relationship with serum potassium. Discontinuation of RAASi therapy exhibited a J‐shaped trend in association with serum potassium. Compared with the reference category (4.5 to <5.0 mmol/L), adjusted IRRs were estimated as 1.07 (0.89–1.28) in patients with serum potassium <3.5 mmol/L, increasing to 1.32 (1.14–1.53) and 2.19 (1.63–2.95) among those with serum potassium ≥5.5 to <6.0 and ≥6.0 mmol/L, respectively. Conclusions In UK patients with new onset heart failure, both hypokalaemia and hyperkalaemia were associated with increased mortality risk, and hyperkalaemia was associated with increased likelihood of RAASi discontinuation. Our results demonstrate the potential importance of serum potassium monitoring for heart failure outcomes and management.

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“…Overall, 100 patients with HF in this study were selected from the EU FP7 funded BIOSTAT‐CHF (A systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure) project. This was a multicentre clinical study in Europe that aimed to identify poor outcomes in HF patients with standard treatment using a systems biology approach (including demographics, biomarkers, genetics, and proteomics) . This project was conducted according to the Declaration of Helsinki that was approved by national and local ethics committees.…”

Section: Methodsmentioning

confidence: 99%

Plasma proteomic approach in patients with heart failure: insights into pathogenesis of disease progression and potential novel treatment targets

Cao

Jones

Voors

et al. 2019

European J of Heart Fail

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Aims To provide insights into pathogenesis of disease progression and potential novel treatment targets for patients with heart failure by investigation of the plasma proteome using network analysis. Methods and results The plasma proteome of 50 patients with heart failure who died or were rehospitalised were compared with 50 patients with heart failure, matched for age and sex, who did not have an event. Peptides were analysed on two‐dimensional liquid chromatography coupled to tandem mass spectrometry (2D LC ESI‐MS/MS) in high definition mode (HDMSE). We identified and quantified 3001 proteins, of which 51 were significantly up‐regulated and 46 down‐regulated with more than two‐fold expression changes in those who experienced death or rehospitalisation. Gene ontology enrichment analysis and protein–protein interaction networks of significant differentially expressed proteins discovered the central role of metabolic processes in clinical outcomes of patients with heart failure. The findings revealed that a cluster of proteins related to glutathione metabolism, arginine and proline metabolism, and pyruvate metabolism in the pathogenesis of poor outcome in patients with heart failure who died or were rehospitalised. Conclusions Our findings show that in patients with heart failure who died or were rehospitalised, the glutathione, arginine and proline, and pyruvate pathways were activated. These pathways might be potential targets for therapies to improve poor outcomes in patients with heart failure.

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Potassium and the use of renin–angiotensin–aldosterone system inhibitors in heart failure with reduced ejection fraction: data from BIOSTAT‐CHF

Abstract: Higher potassium levels are an independent predictor of enduring lower dosages of ACEi/ARB. Higher potassium levels do not attenuate the beneficial effects of ACEi/ARB uptitration.

Cited by 60 publications

References 31 publications

Sex‐ and age‐related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long‐Term Registry

Sex‐ and age‐related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long‐Term Registry

Serum potassium and clinical outcomes in heart failure patients: results of risk calculations in 21 334 patients in the UK

Plasma proteomic approach in patients with heart failure: insights into pathogenesis of disease progression and potential novel treatment targets

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