It is well established that chronic kidney disease (CKD) results in a significant burden on patients’ health and health care providers. However, detailed estimates of the health care resource ...utilization (HCRU) of CKD are limited, particularly those which consider severity, comorbidities, and payer type. This study aimed to bridge this evidence gap by reporting contemporary HCRU and costs in patients with CKD across the US health care providers.
Cost and HCRU estimates of CKD and reduced kidney function without CKD (estimated glomerular filtration rate eGFR: 60−75 and urine albumin-to-creatinine ratio UACR: <30) were derived for US patients included in the DISCOVER CKD cohort study, using linked inpatient and outpatient data from the limited claims-EMR data set (LCED) and TriNetX database. Patients with a history of transplant or undergoing dialysis were not included. HCRU and costs were stratified by CKD severity using UACR and eGFR.
Overall health care costs ranged from $26,889 (A1) to $42,139 (A3), and from $28,627 (G2) to $42,902 (G5) per patient per year (PPPY), demonstrating a considerable early disease burden which continued to increase with declining kidney function. The PPPY costs of later stage CKD were particularly notable for patients with concomitant heart failure ($50,191 A3) and those covered by commercial payers ($55,735 A3).
Health care costs and resource use associated with CKD and reduced kidney function pose a substantial burden across health care systems and payers, increasing in line with CKD progression. Early CKD screening, particularly of UACR, paired with proactive disease management may provide both an improvement to patient outcomes and a significant HCRU and cost saving to health care providers.
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Heart failure (HF) and dementia frequently co-exist with shared pathological mechanisms and risk factors. Our study aims to investigate the association between statin therapy and the risks of ...dementia and its subtypes among patients with HF.
The Hong Kong Clinical Data Analysis and Reporting System database was interrogated to identify patients with incident HF diagnosis from 2004 to 2018, using ICD 9/ICD 10 codes. Inverse probability of treatment weighting (IPTW) was used to balance baseline covariates between statin users (N = 54,004) and non-users (N = 50,291). The primary outcomes were incident all-cause dementia, including subtypes of Alzheimer's disease, vascular dementia, and unspecified dementia. Cox proportional-hazard model with competing risk regression was performed to estimate the sub-distribution hazards ratio (SHR) with corresponding 95% confidence intervals (CI) of the risks of all-cause dementia and its subtypes that are associated with statin use.
Of all eligible patients with HF (N = 104,295), the mean age was 74.2 ± 13.6 years old and 52,511 (50.3%) were male. Over a median follow-up of 9.9 years (interquartile range IQR: 6.4–13.0), 10,031 (9.6%) patients were diagnosed with dementia, among which Alzheimer's disease (N = 2250), vascular dementia (N = 1831), and unspecified dementia (N = 5950) were quantified separately. After IPTW, statin use was associated with a 20% lower risk of incident dementia compared with non-use (multivariable-adjusted SHR 0.80, 95% CI 0.76–0.84). Stratified by subtypes of dementia, statin use was associated with a 28% lower risk of Alzheimer's disease (SHR 0.72, 95% CI 0.63–0.82), 18% lower risk of vascular dementia (SHR 0.82, 95% CI 0.70–0.95), and a 20% lower risk of unspecified dementia (SHR 0.80, 95% CI 0.75–0.85).
In patients with HF, statin use was associated with a significantly lower risk of all-cause dementia and its subtypes, including Alzheimer's disease, vascular dementia, and unspecified dementia. Both randomized trials and experimental studies to validate the potential neuroprotective effect of statin are warranted.
No funding was provided for this study.
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Document Reviewers: Rudolf A. de Boer (CPG Review Coordinator) (Netherlands), P. Christian Schulze (CPG Review Coordinator) (Germany), Magdy Abdelhamid (Egypt), Victor Aboyans (France), Stamatis ...Adamopoulos (Greece), Stefan D. Anker (Germany), Elena Arbelo (Spain), Riccardo Asteggiano (Italy), Johann Bauersachs (Germany), Antoni Bayes-Genis (Spain), Michael A. Borger (Germany), Werner Budts (Belgium), Maja Cikes (Croatia), Kevin Damman (Netherlands), Victoria Delgado (Netherlands), Paul Dendale (Belgium), Polychronis Dilaveris (Greece), Heinz Drexel (Austria), Justin Ezekowitz (Canada), Volkmar Falk (Germany), Laurent Fauchier (France), Gerasimos Filippatos (Greece), Alan Fraser (United Kingdom), Norbert Frey (Germany), Chris P. Gale (United Kingdom), Finn Gustafsson (Denmark), Julie Harris (United Kingdom), Bernard Iung (France), Stefan Janssens (Belgium), Mariell Jessup (United States of America), Aleksandra Konradi (Russia), Dipak Kotecha (United Kingdom), Ekaterini Lambrinou (Cyprus), Patrizio Lancellotti (Belgium), Ulf Landmesser (Germany), Christophe Leclercq (France), Basil S. Lewis (Israel), Francisco Leyva (United Kingdom), AleVs Linhart (Czech Republic), Maja-Lisa Løchen (Norway), Lars H. Lund (Sweden), Donna Mancini (United States of America), Josep Masip (Spain), Davor Milicic (Croatia), Christian Mueller (Switzerland), Holger Nef (Germany), Jens-Cosedis Nielsen (Denmark), Lis Neubeck (United Kingdom), Michel Noutsias (Germany), Steffen E. Petersen (United Kingdom), Anna Sonia Petronio (Italy), Piotr Ponikowski (Poland), Eva Prescott (Denmark), Amina Rakisheva (Kazakhstan), Dimitrios J. Richter (Greece), Evgeny Schlyakhto (Russia), Petar Seferovic (Serbia), Michele Senni (Italy), Marta Sitges (Spain), Miguel Sousa-Uva (Portugal), Carlo G. Tocchetti (Italy), Rhian M. Touyz (United Kingdom), Carsten Tschoepe (Germany), Johannes Waltenberger (Germany/Switzerland) All experts involved in the development of these guidelines have submitted declarations of interest. These have been compiled in a report and published in a supplementary document simultaneously to the guidelines. The report is also available on the ESC website www.escardio.org/guidelines For the Supplementary Data which include background information and detailed discussion of the data that have provided the basis for the guidelines see European Heart Journal online.
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495.
Impact of Geographic Region on the COMMANDER-HF Trial Ferreira, João Pedro; Cleland, John G.F.; Lam, Carolyn S.P. ...
JACC. Heart failure,
March 2021, 2021-03-00, 20210301, 2021-03, Volume:
9, Issue:
3
Journal Article
Peer reviewed
Open access
This study sought to compare patient characteristics, outcomes, and treatment effects among regions in the COMMANDER-HF trial.
Globalization of cardiovascular trials increases generalizability. ...However, regional differences may also introduce heterogeneity in results.
Incidence rates and interactions with treatment were recorded in pre-specified regions: Eastern Europe, Western Europe and South Africa, North America, Asia-Pacific, and Latin America.
Most patients (n = 3,224; 64.2%) were from Eastern Europe; 458 (9.1%) were from Western Europe and South Africa; 149 (3.0%) were from North America; 733 (14.6%) were from Asia-Pacific; and 458 (9.1%) were from Latin America. Compared with patients from Eastern Europe, patients from Western Europe and South Africa, North America, and Asia-Pacific were older and more likely to have coronary interventions and cardiac devices. Patients from Eastern Europe had the lowest event rates. For the primary outcome of myocardial infarction (MI), stroke, or all-cause death, event rates (100/year) were 11.6 in Eastern Europe (10.8 to 12.5); 19.5 (16.5 to 23.0) in Western Europe and South Africa; 14.2 (10.5 to 19.2) in North America; 17.7 (15.4 to 20.3) in Asia-Pacific; and 18.6 (15.6 to 22.1) in Latin America. There was a lower incidence of bleeding in Eastern Europe. Blood concentrations of rivaroxaban (Xarelto, Titusville, New Jersey) at 4 weeks were undetectable in 21% patients from Eastern Europe (n = 128) compared to 5% in other regions (n = 42). There was no evidence of treatment-by-region heterogeneity for the primary outcome (interactionp = 0.14), but a favorable effect on the secondary outcome of MI, stroke, or cardiovascular death was observed in Western Europe and South Africa, North America, and Latin America but not in Eastern Europe and Asia-Pacific (interactionp = 0.017).
In the COMMANDER-HF study, patients from Eastern Europe had a lower risk profile and fewer cardiovascular and bleeding events, possibly related to lower treatment adherence. Those differences might have influenced the effect of rivaroxaban therapy. (A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction or Stroke in Participants With Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure COMMANDER HF; NCT01877915)
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Aims
Recent international heart failure (HF) guidelines recognize anaemia as an important comorbidity contributing to poor outcomes in HF, based on data mainly from Western populations. We sought to ...determine the prevalence, clinical correlates, and prognostic impact of anaemia in patients with HF with reduced ejection fraction across Asia.
Methods and results
We prospectively studied 3886 Asian patients (60 ± 13 years, 21% women) with HF (ejection fraction ≤40%) from 11 regions in the Asian Sudden Cardiac Death in Heart Failure study. Anaemia was defined as haemoglobin <13 g/dL (men) and <12 g/dL (women). Ethnic groups included Chinese (33.0%), Indian (26.2%), Malay (15.1%), Japanese/Korean (20.2%), and others (5.6%). Overall, anaemia was present in 41%, with a wide range across ethnicities (33–54%). Indian ethnicity, older age, diabetes, and chronic kidney disease were independently associated with higher odds of anaemia (all P < 0.001). Ethnicity modified the association of chronic kidney disease with anaemia (Pinteraction = 0.045), with the highest adjusted odds among Japanese/Koreans 2.86; 95% confidence interval (CI) 1.96–4.20. Anaemic patients had lower Kansas City Cardiomyopathy Questionnaire scores (P < 0.001) and higher risk of all‐cause mortality and HF hospitalization at 1 year (hazard ratio = 1.28, 95% CI 1.08–1.50) compared with non‐anaemic patients. The prognostic impact of anaemia was modified by ethnicity (Pinteraction = 0.02), with the greatest hazard ratio in Japanese/Koreans (1.82; 95% CI 1.14–2.91).
Conclusions
Anaemia is present in a third to more than half of Asian patients with HF and adversely impacts quality of life and survival. Ethnic differences exist wherein prevalence is highest among Indians, and survival is most severely impacted by anaemia in Japanese/Koreans.
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Heart failure (HF) is a growing challenge in the Asia Pacific region. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a well-established tool for diagnosis of HF; however, it is relatively ...underutilized in predicting adverse outcomes in HF. Multiple studies have demonstrated the prognostic role of NT-proBNP in HF. A single value of NT-proBNP >5000 pg/mL predicts a worse outcome in hospitalized patients with HF with reduced ejection fraction (HFrEF). In stable outpatients with HFrEF, NT-proBNP > 1000 pg/mL predicts a poorer prognosis. NT-proBNP provides the same prognostic information in patients with HF with preserved ejection fraction (HFpEF) as in those with HFrEF. An expert panel composed of cardiologists mainly from Asia Pacific region was convened to discuss the utility of NT-proBNP in HF prognostication. This article summarizes available scientific evidence and consensus recommendations from the meeting.
Accumulating evidence points to the existence of an inflammatory‐metabolic phenotype of heart failure with a preserved ejection fraction (HFpEF), which is characterized by biomarkers of inflammation, ...an expanded epicardial adipose tissue mass, microvascular endothelial dysfunction, normal‐to‐mildly increased left ventricular volumes and systolic blood pressures, and possibly, altered activity of adipocyte‐associated inflammatory mediators. A broad range of adipogenic metabolic and systemic inflammatory disorders – e.g. obesity, diabetes and metabolic syndrome as well as rheumatoid arthritis and psoriasis – can cause this phenotype, independent of the presence of large vessel coronary artery disease. Interestingly, when compared with men, women are both at greater risk of and may suffer greater cardiac consequences from these systemic inflammatory and metabolic disorders. Women show disproportionate increases in left ventricular filling pressures following increases in central blood volume and have greater arterial stiffness than men. Additionally, they are particularly predisposed to epicardial and intramyocardial fat expansion and imbalances in adipocyte‐associated proinflammatory mediators. The hormonal interrelationships seen in inflammatory‐metabolic phenotype may explain why mineralocorticoid receptor antagonists and neprilysin inhibitors may be more effective in women than in men with HFpEF. Recognition of the inflammatory‐metabolic phenotype may improve an understanding of the pathogenesis of HFpEF and enhance the ability to design clinical trials of interventions in this heterogeneous syndrome.
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Aims
Extracellular vesicles (EVs) are small double‐membrane plasma vesicles that play key roles in cellular crosstalk and mechanisms such as inflammation. The role of EVs in combined organ failure ...such as cardiorenal syndrome has not been investigated. The aim of this study is to identify EV proteins that are associated with renal dysfunction, heart failure, and their combination in dyspnoeic patients.
Methods and results
Blood samples were prospectively collected in 404 patients presenting with breathlessness at the emergency department at National University Hospital, Singapore. Renal dysfunction was defined as estimated glomerular filtration rate < 60 mL/min/1.73 m2. The presence of heart failure was independently adjudicated by two clinicians on the basis of the criteria of the European Society of Cardiology guidelines. Protein levels of SerpinG1, SerpinF2, Cystatin C, and CD14 were measured with a quantitative immune assay within three EV sub‐fractions and in plasma and were tested for their associations with renal dysfunction, heart failure, and the concurrence of both conditions using multinomial regression analysis, thereby correcting for confounders such as age, gender, ethnicity, and co‐morbidities. Renal dysfunction was found in 92 patients (23%), while heart failure was present in 141 (35%). In total, 58 patients (14%) were diagnosed with both renal dysfunction and heart failure. Regression analysis showed that Cystatin C was associated with renal dysfunction, heart failure, and their combination in all three EV sub‐fractions and in plasma. CD14 was associated with both renal dysfunction and the combined renal dysfunction and heart failure in all EV sub‐fractions, and with presence of heart failure in the high density lipoprotein sub‐fraction. SerpinG1 and SerpinF2 were associated with heart failure in, respectively, two and one out of three EV sub‐fractions and in plasma, but not with renal dysfunction.
Conclusions
We provide the first data showing that Cystatin C and CD14 in circulating EVs are associated with both renal dysfunction and heart failure in patients presenting with acute dyspnoea. This suggests that EV proteins may be involved in the combined organ failure of the cardiorenal syndrome and may represent possible targets for prevention or treatment.
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