Risk of hyperkalemia from renin–angiotensin–aldosterone system inhibitors and factors associated with treatment discontinuities in a real-world population

2019 ◽  
Author(s):  
James B Wetmore ◽  
Heng Yan ◽  
Laura Horne ◽  
Yi Peng ◽  
David T Gilbertson
Keyword(s):  
Heart Failure ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
World Population ◽  
Data Set ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Factors Associated ◽  
Treatment Interruptions ◽  
Ckd Stage

Abstract Background Hyperkalemia rates in renin–angiotensin–aldosterone system (RAAS) inhibitor users, and factors associated with treatment interruptions and cessations, have not been explored in a large, population-wide database. Methods RAAS inhibitor users were identified in the linked UK Clinical Practice Research Datalink-Hospital Episodes Statistics data set, 2009–15. Treatment interruptions (no active prescription followed by reappearance) and cessations were determined. Hyperkalemia (serum K+>5.5 mmol/L) rates were calculated and factors associated with interruptions and cessations modeled using time-varying Cox regression, including hyperkalemia (as a time-dependent variable). Results Among 434 027 RAAS inhibitor users, the hyperkalemia rate was 1.30 (95% confidence interval 1.28–1.32) per 100 patient-years. Of 73.7% of patients who experienced off-treatment periods, 57.6% experienced interruption only, 7.5% cessation only and 8.6% both. Within 1 year of initiating RAAS inhibitor treatment, approximately one-third of the patients experienced interruption or cessation. Hazard ratios for patients with severe hyperkalemia were 1.10 (10.5–1.16) for interruptions and 3.37 (3.25–3.50) for cessation. Compared with no chronic kidney disease (CKD), risk of interruption was 1.20 (1.16–1.25) and 1.57 (1.44–1.72) for Stages 4 and 5, respectively, and of cessation was 2.20 (2.07–2.33) and 2.87 (2.56–3.22). Risk of interruption increased for patients with heart failure or diabetes [1.04 (1.02–1.05); 1.13 (1.12–1.14), respectively] but the risk of cessation decreased [0.85 (0.82–0.87); 0.92 (0.90–0.94)]. Conclusions Risk of RAAS inhibitor interruption and cessation increased as CKD stage progressed. Efforts targeting reasons for interruptions and, especially, cessations, such as hyperkalemia prevention, could decrease off-treatment periods for patients who would otherwise benefit, such as those with CKD, heart failure or diabetes.

scholarly journals Adverse clinical outcomes associated with RAAS inhibitor discontinuation: analysis of over 400 000 patients from the UK Clinical Practice Research Datalink (CPRD)

2021 ◽  
Author(s):  
Toby J L Humphrey ◽  
Glen James ◽  
Eric T Wittbrodt ◽  
Donna Zarzuela ◽  
Thomas F Hiemstra
Keyword(s):  
Heart Failure ◽  
Acute Kidney Injury ◽  
Clinical Practice ◽  
Clinical Outcomes ◽  
Kidney Injury ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Ckd Stage ◽  
First Occurrence ◽  
Baseline Characteristics

Abstract Background Users of guideline-recommended renin–angiotensin–aldosterone system (RAAS) inhibitors may experience disruptions to their treatment, e.g. due to hyperkalaemia, hypotension or acute kidney injury. The risks associated with treatment disruption have not been comprehensively assessed; therefore, we evaluated the risk of adverse clinical outcomes in RAAS inhibitor users experiencing treatment disruptions in a large population-wide database. Methods This exploratory, retrospective analysis utilized data from the UK’s Clinical Practice Research Datalink, linked to Hospital Episodes Statistics and the Office for National Statistics databases. Adults (≥18 years) with first RAAS inhibitor use (defined as angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) between 1 January 2009 and 31 December 2014 were eligible for inclusion. Time to the first occurrence of adverse clinical outcomes [all-cause mortality, all-cause hospitalization, cardiac arrhythmia, heart failure hospitalization, cardiac arrest, advancement in chronic kidney disease (CKD) stage and acute kidney injury] was compared between RAAS inhibitor users with and without interruptions or cessations to treatment during follow-up. Associations between baseline characteristics and adverse clinical outcomes were also assessed. Results Among 434 027 RAAS inhibitor users, the risk of the first occurrence of all clinical outcomes, except advancement in CKD stage, was 8–75% lower in patients without interruptions or cessations versus patients with interruptions/cessations. Baseline characteristics independently associated with increased risk of clinical outcomes included increasing age, smoking, CKD, diabetes and heart failure. Conclusions These findings highlight the need for effective management of factors associated with RAAS inhibitor interruptions or cessations in patients for whom guideline-recommended RAAS inhibitor treatment is indicated.

scholarly journals Use of Renin–Angiotensin–Aldosterone System Inhibitors in Older Patients with Heart Failure and Reduced Ejection Fraction

2019 ◽  
Vol 5 (2) ◽  
pp. 70-73 ◽  
Author(s):  
Davide Stolfo ◽  
Gianluigi Savarese
Keyword(s):  
Heart Failure ◽  
Clinical Trials ◽  
Ejection Fraction ◽  
Older Patients ◽  
Randomised Clinical Trials ◽  
World Population ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Reduced Ejection Fraction ◽  
Raas Inhibitors

Patients enrolled in randomised clinical trials may not be representative of the real-world population of people with heart failure (HF). Older patients are frequently excluded and this limits the strength of evidence which supports the use of specific HF treatments in this patient group. Lack of evidence together with fear of adverse effects, drug interactions and lower tolerance may lead to the undertreatment of older patients and a less favourable outcome. Renin–angiotensin–aldosterone system (RAAS) inhibitors are the cornerstone of treatment for patients with HF with reduced ejection fraction (HFrEF), but despite the class I recommendation for all patients regardless of age in the guidelines, there are signs that RAAS inhibitors are underused among older patients. Large registry- based studies suggest that RAAS inhibitors may be at least as effective in older patients as younger ones, but these findings need to be confirmed by randomised clinical trials.

The relationship between duration of heart failure, serum potassium concentration and adverse clinical outcomes

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P McEwan ◽  
M Hurst ◽  
L Hoskin ◽  
K Badora ◽  
D Sugrue ◽  
...  
Keyword(s):  
Heart Failure ◽  
Clinical Outcomes ◽  
Serum Potassium ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Funding Source ◽  
Private Company ◽  
Increased Risk ◽  
Ckd Stage ◽  
The Relationship

Abstract Background Hyper- and hypokalaemia are frequent complications in patients with heart failure (HF). The association between all-cause mortality (ACM), major adverse cardiovascular events (MACE) and serum potassium (K+) has previously been characterised in a UK incident HF population, with hypo- and hyperkalaemic patients being at increased risk of adverse clinical outcomes. Purpose This study aimed to assess the generalisability and findings of previously published risk equations in a broader HF population, spanning both incident and prevalent HF cases regardless of chronic kidney disease (CKD), and to explore the relationship between duration of HF and elevated risk associated with hypo- or hyperkalaemia. Methods A retrospective cohort study was conducted using linked UK Clinical Practice Research Datalink (CPRD) GOLD and Hospital Episode Statistics (HES) data. Eligible patients included individuals ≥18 years with HF (identified using READ codes) during the study period (January 2008 to June 2018) or five-year lookback period (2003 to 2007). Patients' index date was set to 1st January 2008 for prevalent patients or date of HF diagnosis for incident patients. Adverse clinical outcomes included ACM and MACE, a composite of arrhythmia, HF, myocardial infarction and stroke. Published risk equations for ACM and MACE for incident HF without CKD were refitted to this broader study population using original covariates and model forms. Coefficient values were adjusted for the inclusion of HF duration (≤5 and >5 years). Incidence rate ratios (IRRs) were recalculated with K+ concentration 4.5 to <5.0 mmol/L as the reference category. Results The HF cohort consisted of 84,210 patients with a mean follow-up of 5.01 years. The cohort was predominantly male (53.0%), with a mean age of 77.3 years at index. Ischaemic heart disease, hypertension, atrial fibrillation and type 2 diabetes were present in 42.24%, 61.39%, 40.89% and 20.38% of the population, respectively. CKD stage 3+ was present in 39.13% of patients, with a cohort mean estimated glomerular filtration rate of 56.9 mL/min/1.73m2 at index. Crude ACM and MACE event rates were 159.5 (95% confidence interval (CI): 157.9–161.0) and 575.8 (95% CI: 572.8–578.7) per 1,000 patient years, respectively. Hypo- and hyperkalaemia were generally associated with increased risk of ACM and MACE in comparison with patients with K+ concentrations of 4.5 to <5.0 mmol/L (figure 1); these associations were maintained irrespective of the duration of HF. Conclusion A real-world analysis of UK patients suggests that previously published associations between hypo- and hyperkalaemia and increased risk of adverse clinical outcomes in an incident HF population are generalisable to a cohort of incident and prevalent HF patients, irrespective of HF duration and the presence of comorbid CKD. Improved monitoring and management of K+ may have the potential to improve outcomes in these patients. Figure 1. IRRs of ACM and MACE Funding Acknowledgement Type of funding source: Private company. Main funding source(s): AstraZeneca

scholarly journals Real-world presentation with heart failure in primary care: do patients selected to follow diagnostic and management guidelines have better outcomes?

Open Heart ◽  
2018 ◽  
Vol 5 (2) ◽  
pp. e000935
Author(s):  
Alex Bottle ◽  
Dani Kim ◽  
Paul P Aylin ◽  
F Azeem Majeed ◽  
Martin R Cowie ◽  
...  
Keyword(s):  
Heart Failure ◽  
Primary Care ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Initial Management ◽  
Risk Of Death ◽  
Specialist Referral ◽  
Partial Completion ◽  
General Practices ◽  
Using Data

ObjectiveTo describe associations between initial management of people presenting with heart failure (HF) symptoms in primary care, including compliance with the recommendations of the National Institute for Health and Care Excellence (NICE), and subsequent unplanned hospitalisation for HF and death.MethodsThis is a retrospective cohort study using data from general practices submitting records to the Clinical Practice Research Datalink. The cohort comprised patients diagnosed with HF during 2010–2013 and presenting to their general practitioners with breathlessness, fatigue or ankle swelling.Results13 897 patients were included in the study. Within the first 6 months, only 7% had completed the NICE-recommended pathway; another 18.6% had followed part of it (B-type natriuretic peptide testing and/or echocardiography, or specialist referral). Significant differences in hazards were seen in unadjusted analysis in favour of full or partial completion of the NICE-recommended pathway. Covariate adjustment attenuated the relations with death much more than those for HF admission. Compared with patients placed on the NICE pathway, treatment with HF medications had an HR of 1.16 (95% CI 1.05 to 1.28, p=0.003) for HF admission and 1.03 (95% CI 0.90 to 1.17, p= 0.674) for death. Patients who partially followed the NICE pathway had similar hazards to those who completed it. Patients on no pathway had the highest hazard for HF admission at 1.30 (95% 1.18 to 1.43, p<0.001) but similar hazard for death.ConclusionsPatients not put on at least some elements of the NICE-recommended pathway had significantly higher risk of HF admission but non-significant higher risk of death than other patients had.

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