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 Estimating the risk of acute kidney injury associated with use of diuretics and renin angiotensin aldosterone system inhibitors: A population based cohort study using the clinical practice research datalink

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Jemima Scott ◽  
Tim Jones ◽  
Maria Theresa Redaniel ◽  
Margaret T. May ◽  
Yoav Ben-Shlomo ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Cohort Study ◽  
Clinical Practice ◽  
Propensity Score ◽  
Cox Regression ◽  
Kidney Injury ◽  
Exposed Group ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Raas Inhibitors

Abstract Background The risk of acute kidney injury (AKI) attributable to renin angiotensin aldosterone (RAAS) inhibitors and diuretics remains unclear. Methods We conducted a prospective cohort study using the Clinical Practice Research Datalink (2008–2015) linked to Hospital Episode Statistics – Admitted Patient Care and Office for National Statistics mortality data. Patients were included if they had one or more chronic diagnoses requiring medication. Exposed patients had a first ever prescription for RAAS inhibitors/diuretics during the study period. AKI risk associated with exposure was determined by multivariable Cox regression, propensity score-adjusted Cox regression and a prior event rate ratio (PERR) analysis. Results One hundred forty thousand nine hundred fifty-two individuals were included. Increased AKI risk in the exposed group was demonstrated in both the multivariable and propensity score-adjusted cox regressions (HR 1.23 (95% CI 1.04–1.45) and HR 1.24 (1.05–1.47) respectively). The PERR analysis provided a similar overall hazard ratio with a wider confidence interval (HR 1.29 (0.94–1.63)). The increased AKI risk in the exposed group was present only in those receiving two or more antihypertensives. Absolute AKI risk was small. Conclusions RAAS inhibitors/diuretics result in an increased risk of AKI. The absolute increase in AKI risk is small, however, and needs to be considered in the context of any potential benefits.

scholarly journals Long-term effects of bariatric surgery on acute kidney injury: a propensity-matched cohort in the UK Clinical Practice Research Datalink

BMJ Open ◽  
2018 ◽  
Vol 8 (5) ◽  
pp. e020371
Author(s):  
Uwe Koppe ◽  
Dorothea Nitsch ◽  
Kathryn E Mansfield ◽  
Rohini Mathur ◽  
Krishnan Bhaskaran ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Acute Kidney Injury ◽  
Clinical Practice ◽  
Kidney Injury ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Matched Cohort ◽  
Long Term Effects ◽  
The Uk

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 TO019PROGNOSTIC VALUE OF ACUTE KIDNEY INJURY AND HEMOCONCENTRATION DURING ACUTE HEART FAILURE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yannis Lombardi ◽  
Franck Boccara ◽  
Kadiatou Baldet ◽  
Stéphane Ederhy ◽  
Pascal Nhan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Acute Kidney Injury ◽  
Clinical Practice ◽  
Prognostic Value ◽  
Serum Proteins ◽  
Kidney Injury ◽  
Hospital Entry ◽  
Furosemide Administration ◽  
Transient Aki

Abstract Background and Aims Acute kidney injury (AKI) occurring after diuretic treatment initiation for acute heart failure (AHF) is a common phenomenon, with an incidence estimated between 20 and 50% of AHF hospitalizations. Previous studies found that persistent AKI is associated with poor prognosis. Treatment-induced hemoconcentration is associated with improved prognosis, but several definitions previously used are not suited for clinical practice. Transient AKI, with or without hemoconcentration, is of unsettled prognosis. We aim to determine the independent prognostic value of transient AKI, persistent AKI and hemoconcentration in the context of AHF hospitalization, using practical definitions. Method Data were obtained from the Greater Paris University Hospitals (GPUH) Clinical Data Warehouse. Patients hospitalized for AHF in various GPUH units were included. AHF hospitalization was defined as hospitalization with at least one AHF ICD-10 code and at least one recorded furosemide administration. Bumetanide is rarely used in GPUH hospitals hence it was not considered. AKI in a period of 14 days following first furosemide administration was defined based on KDIGO guidelines. Hemoconcentration was defined as an increase in serum proteins ≥ 5 g/l during the same period. Multivariate logistic regression was performed to determine which characteristics were predictive of AKI. Cox regression of 100 days all-cause mortality using multiple confounders was performed to determine the prognostic value of transient AKI (< 14 days), persistent AKI (≥ 14 days) and hemoconcentration. Patients with AKI upon hospital entry were excluded from regression analyses. AKI and hemoconcentration were treated as time-dependent covariates to adjust for immortality bias. Results Five hundred seventy nine patients were included. Among them, 529 had no AKI upon hospital entry and 513 had at least one recorded serum proteins and creatinine value following furosemide initiation. Median follow-up was 114 days. AKI in a period of 14 days following furosemide initiation occurred in 234 patients (40.4%). At baseline, patients in the AKI group more frequently suffered from chronic kidney disease or presented with clinical and echocardiographic signs of right heart failure. Independent predictors of AKI were arterial hypertension upon furosemide initiation (adjusted OR 1.86 [1.08 – 3.22]), elevated serum creatinine upon furosemide initiation (adjusted OR 1.07 [1.01 – 1.14] per 10 µmol/l increase) and initial intravenous administration of furosemide (adjusted OR 2.42 [1.39 – 4.29]). Death during follow-up occurred in 35% of patients in the AKI group compared to 21% in the non-AKI group (p < 0.001). In multivariate analysis, persistent AKI was independently associated with increased mortality in a period of 100 days following furosemide initiation (adjusted HR 2.31 [1.07 – 4.99]). Transient AKI was not significantly associated with mortality (adjusted HR 0.64 [0.34 – 1.19]). Hemoconcentration was independently associated with decreased mortality (adjusted HR 0.46 [0.27 – 0.79]). Conclusion After furosemide initiation during hospitalization for AHF, persistent AKI (≥ 14 days) was independently associated with increased 100 days mortality. Hemoconcentration, using a definition suited for clinical practice (≥ 5 g/l increase in serum proteins), was independently associated with decreased 100 days mortality. No significant association was found between mortality and transient AKI (< 14 days). Those findings show that laboratory tests at a limited cost – serum proteins and creatinine – are helpful to evaluate treatment response and mortality risk during AHF. Prospective randomized controlled trials are needed to establish diuretic strategies based on both AKI and hemoconcentration.

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 Association between chronic kidney disease and incident diagnosis of dementia in England: a cohort study in Clinical Practice Research Datalink

BMJ Open ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. e033811
Author(s):  
Rikako Hiramatsu ◽  
Masao Iwagami ◽  
Dorothea Nitsch
Keyword(s):  
Clinical Practice ◽  
Secondary Outcome ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Matched Cohort ◽  
Dementia Diagnosis ◽  
Risk Of Mortality ◽  
Incident Dementia ◽  
Ckd Stage ◽  
Diagnosis Of Dementia

ObjectivesTo investigate the association between chronic kidney disease (CKD) and dementia diagnosis in a real-world primary care setting in England.DesignMatched cohort study.SettingsEnglish primary care in the Clinical Practice Research Datalink.ParticipantsPeople aged ≥18 years with predialysis CKD (stages 3–5, defined as two measurements of estimated glomerular filtration rate <60 mL/min/1.73 m2 for 3 months) from 2004 to 2014, and people without known CKD who were matched on age, sex, general practice and calendar time in a 1:1 ratio.Primary and secondary outcome measuresFirst-ever diagnosis of dementia recorded by GPs. We also examined all-cause death as a secondary outcome to discuss potential competing risk of mortality in the association between CKD and dementia diagnosis.ResultsIn a matched cohort of 242 349 pairs with and without CKD (mean age 75.4±9.7 years, 39.3% male), the crude incidence rate of dementia diagnosis was 11.4/1000 and 9.4/1000 person-years, respectively. There was an association between CKD status and incident dementia diagnosis in the first 6 months of the follow-up (adjusted rate ratio (aRR) 1.58, 95% CI 1.44 to 1.74), which attenuated after 6 months (aRR 1.12, 95% CI 1.08 to 1.16). Among patients with CKD, there was no evidence of association between CKD stage and incident dementia diagnosis; compared with stage 3a, aRR (95% CI) was 1.04 (0.91 to 1.18) for stage 3b and 0.94 (0.74 to 1.20) for stages 4 or 5 in the first 6 months, and 0.97 (0.92 to 1.01) and 0.89 (0.80 to 0.98) thereafter. We found a strong association between worsening CKD stage and all-cause mortality.ConclusionWe identified a co-occurrence of detection of CKD and dementia in real-world clinical practice and a strong competing risk of mortality in the association between CKD stage and dementia, while a weak association between CKD status and dementia was suggested in the long term.

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