- Email: [email protected]
Roadmap for cardiovascular prevention trials in chronic kidney disease
Comment
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Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361: 1045–57. Aradi D, Kirtane A, Bonello L, et al. Bleeding and stent thrombosis on P2Y12-inhibitors: collaborative analysis on the role of platelet reactivity for risk stratification after percutaneous coronary intervention. Eur Heart J 2015; 36: 1762–71. Tantry US, Bonello L, Aradi D, et al. Consensus and update on the definition of on-treatment platelet reactivity to adenosine diphosphate associated with ischemia and bleeding. J Am Coll Cardiol 2013; 62: 2261–73. Collet JP, Cuisset T, Range G, et al. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med 2012; 367: 2100–09. Aradi D, Storey RF, Komocsi A, et al. Expert position paper on the role of platelet function testing in patients undergoing percutaneous coronary intervention. Eur Heart J 2014; 35: 209–15. Cayla G, Cuisset T, Silvain J, et al. Platelet function monitoring to adjust antiplatelet therapy in elderly patients stented for an acute coronary syndrome (ANTARCTIC): an open-label, blinded-endpoint, randomised controlled superiority trial. Lancet 2016; published online Aug 28. http://dx.doi.org/10.1016/S0140-6736(16)31323-X. Roe MT, Goodman SG, Ohman EM, et al. Elderly patients with acute coronary syndromes managed without revascularization: insights into the safety of long-term dual antiplatelet therapy with reduced-dose prasugrel versus standard-dose clopidogrel. Circulation 2013; 128: 823–33.
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Erlinge D, Gurbel PA, James S, et al. Prasugrel 5 mg in the very elderly attenuates platelet inhibition but maintains noninferiority to prasugrel 10 mg in nonelderly patients: the GENERATIONS trial, a pharmacodynamic and pharmacokinetic study in stable coronary artery disease patients. J Am Coll Cardiol 2013; 62: 577–83. Qaderdan K, Ishak M, Heestermans AA, et al. Ticagrelor or prasugrel versus clopidogrel in elderly patients with an acute coronary syndrome: optimization of antiplatelet treatment in patients 70 years and older-rationale and design of the POPular AGE study. Am Heart J 2015; 170: 981–85.e1. Gurbel PA, Erlinge D, Ohman EM, et al. Platelet function during extended prasugrel and clopidogrel therapy for patients with ACS treated without revascularization: the TRILOGY ACS platelet function substudy. JAMA 2012; 308: 1785–94. Sibbing D, Steinhubl SR, Schulz S, Schomig A, Kastrati A. Platelet aggregation and its association with stent thrombosis and bleeding in clopidogrel-treated patients: initial evidence of a therapeutic window. J Am Coll Cardiol 2010; 56: 317–18.
Roadmap for cardiovascular prevention trials in chronic kidney disease
beaubelle/Fotolia
Cardiovascular death is a leading cause of death in patients with chronic kidney disease, and the risk of cardiovascular mortality, adjusted for traditional cardiovascular risk factors and albuminuria, is linearly and negatively correlated with renal function.1 In patients with end-stage renal disease who are on dialysis, cardiovascular mortality is 10 to 20 times higher than in the general population and, among adults younger than 45 years, mortality rates are approximately 100 times higher than in the general population.2 Hence, treatments to improve mortality and specifically cardiovascular outcomes in this population are greatly needed. In recent years, treatment of cardiovascular diseases has had important advances; however, evidence-based strategies for improving cardiovascular outcomes in patients with advanced chronic kidney disease remain almost unavailable. This is in part because the efficacy and safety studies that support drug approval typically exclude patients with more advanced chronic kidney disease; although criteria vary, typically patients with stage 4 and 5 chronic kidney disease are excluded from cardiovascular outcome studies. This is also because very few adequately powered cardiovascular outcome trials that focus specifically on patients with advanced chronic kidney disease have been done.3–5 Additionally, a reverse epidemiology of classic cardiovascular risk factors has 1964
been described in patients with end-stage renal disease,2 raising substantial concern about extrapolation of evidence-based cardiovascular prevention strategies in patients without end-stage renal disease to patients with end-stage renal disease. For example, in contrast to the general population, a higher body-mass index is associated with better survival in patients with endstage renal disease; similar findings have been reported for cholesterol and blood pressure.6 There are major challenges with undertaking cardiovascular outcome trials in patients with advanced stages of chronic kidney diseases (ie, stage 4–5 disease) and those who are on dialysis. One key issue is how to define cardiovascular events such as acute coronary syndrome and heart failure in patients with later stages of chronic kidney diseases, including end-stage renal disease, and whether the developed standardised definitions for cardiovascular endpoints7 are well suited for this population. For the diagnosis of myocardial infarction, the recommendation is to base thresholds for biomarker detection of myocardial infarction on 99th percentile values,7 and for cardiac biomarkers to be negative to fulfil the criteria7 for the diagnosis of unstable angina. However, baseline troponin concentrations are often elevated in patients with chronic kidney disease, while serial changes in dialysis patients with frequently and www.thelancet.com Vol 388 October 22, 2016
Comment
chronically elevated (even >99th percentile values) cardiac troponin have uncertain clinical implications and are difficult to interpret.8,9 Are specific thresholds— that take into consideration the stage of chronic kidney disease to assessing changes in troponin over time—needed to diagnose myocardial infarction and unstable angina in patients with more advanced chronic kidney disease and, if so, what should they be? Also, what criteria should be used to reliably distinguish a real heart failure admission from the unfortunate but common occurrence of transient fluid overload related to dry weight overestimation or nonadherence to diet in dialysis patients? Finally, what outcomes should we be focusing on in clinical trials in this population, particularly in trials of haemodialysis patients, in which predominant modes of cardiovascular death might differ from those observed in patients with chronic kidney disease but non-end-stage renal disease? Among patients with end-stage renal disease covered by Medicare, 37% of all deaths have been attributed to sudden death or cardiac arrhythmias and, in haemodialysis patients, unique factors, such as electrolyte shifts, contribute to these deaths.10,11 To target patients at higher risk for cardiovascular events for enrolment in clinical trials (prognostic enrichment) improves the ability to detect a treatment benefit in cardiovascular outcome trials, if such a benefit exists. Unfortunately, methods to identify patients with advanced chronic kidney disease who are likely to have adverse cardiovascular outcomes are inadequate. Additionally, although patients with chronic kidney disease are at high risk for cardiovascular death, they also have high rates of other causes of death, including sepsis and cancer.12 Better risk models are needed to identify patients who are likely to have particular adverse cardiovascular outcomes of interest and unlikely to die from a non-cardiovascular cause. Optimal statistical strategies for addressing competing risks also need to be considered. An agenda for further research should be encouraged, with the aim of validating traditional and potentially non-traditional cardiovascular risk markers in this population, and validating markers or combinations of markers that can be used to identify subsets of patients who might be more or less likely to respond to particular types of interventions. Relating to this issue, clinical trials in patients with a reduced ejection fraction have often used New York Heart www.thelancet.com Vol 388 October 22, 2016
Association classification, plasma B-type natriuretic peptide concentrations, ejection fraction, and a history of admissions to hospital for heart failure within some timeframe relative to the start of the trial to identify patients who have the condition of interest and who are likely to have the outcome of interest during the course of the trial. Will an enrichment strategy based on these same variables be effective in heart failure trials in patients with stage 4 or 5 chronic kidney disease, or does the volume overload resulting from diminished renal function limit our ability to use these variables to enrich the trial population? How can we best use measures of calcification or uraemic burden to identify subpopulations that might be likely to respond to interventions aimed at particular pathways that might be unique to advanced chronic kidney disease, and what outcomes should trials of such interventions target? Existing data should be leveraged to answer these and other questions. It is widely recognised that the rates of cardiovascular morbidity and mortality seen in patients with advanced stages of chronic kidney diseases are unacceptable. It is high time for nephrologists, cardiologists, clinical trialists, statisticians, industry, and regulators to come together to develop a roadmap to address the barriers discussed, as well as others, to do trials in this population. *Patrick Rossignol, Bertram Pitt, Aliza Thompson, Faiez Zannad Inserm 1433, Centre d’Investigations Cliniques-Plurithématique, Université de Lorraine, CHU Nancy, 54500 France (PR, FZ); F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France (PR, FZ); Association Lorraine de Traitement de l’Insuffisance Rénale, Nancy, France (PR); University of Michigan School of Medicine, Ann Arbor, MI, USA (BP); and Division of Cardiovascular and Renal Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA (AT) [email protected] AT is an employee of the FDA. This Comment reflects the views of the authors and should not be construed to represent the FDA’s views or policies. AT declares no other competing interests. PR has received personal fees from CVRx, Novartis, Relypsa, AstraZeneca, Vifor Fresenius Medical Care Renal Pharma, and Stealth Peptides, and is co-founder of Cardiorenal, a private company aimed at developing a telemonitoring loop for heart failure, outside the submitted work. BP has received personal fees from Bayer, Merck, AstraZeneca, Takeda, Relypsa, scPharmaceuticals, KBP Pharmaceuticals, PharMain, Tricida, and daVinci Therapeutics. FZ has received personal fees from Janssen, Bayer, Pfizer, Novartis, Boston Scientific, Resmed, Amgen, CVRx, Quantum Genomics, AstraZeneca, Eli Lilly, Relypsa, ZS Pharma, and Takeda, and is co-founder of Cardiorenal. 1
2
Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, et al. Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet 2013; 382: 339–52. Ortiz A, Covic A, Fliser D, et al. Epidemiology, contributors to, and clinical trials of mortality risk in chronic kidney failure. Lancet 2014; 383: 1831–43.
1965
Comment
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4
5
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Konstantinidis I, Nadkarni GN, Yacoub R, et al. Representation of patients with kidney disease in trials of cardiovascular interventions: an updated systematic review. JAMA Intern Med 2016; 176: 121–24. Zannad F, Kessler M, Lehert P, et al. Prevention of cardiovascular events in end-stage renal disease: results of a randomized trial of fosinopril and implications for future studies. Kidney Int 2006; 70: 1318–24. Fellstrom BC, Jardine AG, Schmieder RE, et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med 2009; 360: 1395–407. Rossignol P, Cridlig J, Lehert P, Kessler M, Zannad F. Visit-to-visit blood pressure variability is a strong predictor of cardiovascular events in hemodialysis: insights from FOSIDIAL. Hypertension 2012; 60: 339–46. Hicks KA, Tcheng JE, Bozkurt B, et al. 2014 ACC/AHA key data elements and definitions for cardiovascular endpoint events in clinical trials: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop Cardiovascular Endpoints Data Standards). Circulation 2015; 132: 302–61.
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12
Sandoval Y, Herzog CA, Love SA, et al. Prognostic value of serial changes in high-sensitivity cardiac troponin I and T over 3 months using reference change values in hemodialysis patients. Clin Chem 2016; 62: 631–38. Badiou S, Boudet A, Leray-Moragues H, et al. Monthly reference change value of cardiac troponin in hemodialysis patients as a useful tool for long-term cardiovascular management. Clin Biochem 2016; published online May 20. DOI:10.1016/j.clinbiochem.2016.05.015. Green D, Roberts PR, New DI, Kalra PA. Sudden cardiac death in hemodialysis patients: an in-depth review. Am J Kidney Dis 2011; 57: 921–29. United States Renal Data System. 2015 USRDS annual data report: epidemiology of kidney disease in the United States. Bethesda, MD, USA: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2015. Vanholder R, Fouque D, Glorieux G, et al. Clinical management of the uraemic syndrome in chronic kidney disease. Lancet Diabetes Endocrinol 2016; 4: 360–73.
Improving outcomes of dialysis patients by population health management—the Global Chief Medical Officer Initiative
Life in View/Science Photo Library
Renal replacement therapy (RRT) by dialysis is a lifesustaining treatment that globally enables almost 3 million patients with end-stage renal disease to survive while maintaining daily activities of living.1 Despite technical progress in dialysis machines and dialyser performance, better understanding of uraemic pathophysiology, improvement in dialysis tolerance, and better management of anaemia and other comorbidities, patients have a high burden of chronic illness with substantial morbidity and mortality. Appropriate care of patients with end-stage renal disease includes collection of fundamental dialysis metrics, as well as those associated with management of comorbid disorders. Dialysis allows for systematic collection of clinical data across different care settings. Analysis of these data has the potential for
1966
population health management by revealing opportunities to improve patients’ care and to reduce costs.2 Worldwide there are increasing demands for RRT services, regional shortages of skilled caregivers, and constraints on funding. Ensuring quality of care, value-based delivery (defined as outcomes and service relative to costs), and meeting costs for end-stage renal disease are an increasing concern.3–5 There is a need for integrated care management of patients with advanced renal disease to optimise transitions of care (eg, initiation of RRT, post-acute hospitalisation care management), develop cost-effective alternative therapies and care structures, increase renal transplantation rates, and reduce the costs associated with caring for patients. These issues have led to an initiative by the Chief Medical Officers (CMO) of dialysis organisations in the USA to improve the quality of dialysis care.5,6 And now the CMOs of dialysis service providers operating dialysis clinics on five continents (the USA, South America, Europe, Asia, Oceania)—covering more than two-thirds of renal care providers—are collaborating to share their clinical expertise to harmonise the various clinical data definitions used in end-stage renal disease quality management through the Global CMO Initiative. In addition to harmonisation of data definitions, the group is dedicated to improving care and outcomes for dialysis patients worldwide by identifying, sharing, and promoting implementation of known best clinical practices in their clinic networks. Those taking part in the Global CMO Initiative aim to identify, discuss, and promote best practices for data www.thelancet.com Vol 388 October 22, 2016
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Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361: 1045–57. Aradi D, Kirtane A, Bonello L, et al. Bleeding and stent thrombosis on P2Y12-inhibitors: collaborative analysis on the role of platelet reactivity for risk stratification after percutaneous coronary intervention. Eur Heart J 2015; 36: 1762–71. Tantry US, Bonello L, Aradi D, et al. Consensus and update on the definition of on-treatment platelet reactivity to adenosine diphosphate associated with ischemia and bleeding. J Am Coll Cardiol 2013; 62: 2261–73. Collet JP, Cuisset T, Range G, et al. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med 2012; 367: 2100–09. Aradi D, Storey RF, Komocsi A, et al. Expert position paper on the role of platelet function testing in patients undergoing percutaneous coronary intervention. Eur Heart J 2014; 35: 209–15. Cayla G, Cuisset T, Silvain J, et al. Platelet function monitoring to adjust antiplatelet therapy in elderly patients stented for an acute coronary syndrome (ANTARCTIC): an open-label, blinded-endpoint, randomised controlled superiority trial. Lancet 2016; published online Aug 28. http://dx.doi.org/10.1016/S0140-6736(16)31323-X. Roe MT, Goodman SG, Ohman EM, et al. Elderly patients with acute coronary syndromes managed without revascularization: insights into the safety of long-term dual antiplatelet therapy with reduced-dose prasugrel versus standard-dose clopidogrel. Circulation 2013; 128: 823–33.
9
10
11
12
Erlinge D, Gurbel PA, James S, et al. Prasugrel 5 mg in the very elderly attenuates platelet inhibition but maintains noninferiority to prasugrel 10 mg in nonelderly patients: the GENERATIONS trial, a pharmacodynamic and pharmacokinetic study in stable coronary artery disease patients. J Am Coll Cardiol 2013; 62: 577–83. Qaderdan K, Ishak M, Heestermans AA, et al. Ticagrelor or prasugrel versus clopidogrel in elderly patients with an acute coronary syndrome: optimization of antiplatelet treatment in patients 70 years and older-rationale and design of the POPular AGE study. Am Heart J 2015; 170: 981–85.e1. Gurbel PA, Erlinge D, Ohman EM, et al. Platelet function during extended prasugrel and clopidogrel therapy for patients with ACS treated without revascularization: the TRILOGY ACS platelet function substudy. JAMA 2012; 308: 1785–94. Sibbing D, Steinhubl SR, Schulz S, Schomig A, Kastrati A. Platelet aggregation and its association with stent thrombosis and bleeding in clopidogrel-treated patients: initial evidence of a therapeutic window. J Am Coll Cardiol 2010; 56: 317–18.
Roadmap for cardiovascular prevention trials in chronic kidney disease
beaubelle/Fotolia
Cardiovascular death is a leading cause of death in patients with chronic kidney disease, and the risk of cardiovascular mortality, adjusted for traditional cardiovascular risk factors and albuminuria, is linearly and negatively correlated with renal function.1 In patients with end-stage renal disease who are on dialysis, cardiovascular mortality is 10 to 20 times higher than in the general population and, among adults younger than 45 years, mortality rates are approximately 100 times higher than in the general population.2 Hence, treatments to improve mortality and specifically cardiovascular outcomes in this population are greatly needed. In recent years, treatment of cardiovascular diseases has had important advances; however, evidence-based strategies for improving cardiovascular outcomes in patients with advanced chronic kidney disease remain almost unavailable. This is in part because the efficacy and safety studies that support drug approval typically exclude patients with more advanced chronic kidney disease; although criteria vary, typically patients with stage 4 and 5 chronic kidney disease are excluded from cardiovascular outcome studies. This is also because very few adequately powered cardiovascular outcome trials that focus specifically on patients with advanced chronic kidney disease have been done.3–5 Additionally, a reverse epidemiology of classic cardiovascular risk factors has 1964
been described in patients with end-stage renal disease,2 raising substantial concern about extrapolation of evidence-based cardiovascular prevention strategies in patients without end-stage renal disease to patients with end-stage renal disease. For example, in contrast to the general population, a higher body-mass index is associated with better survival in patients with endstage renal disease; similar findings have been reported for cholesterol and blood pressure.6 There are major challenges with undertaking cardiovascular outcome trials in patients with advanced stages of chronic kidney diseases (ie, stage 4–5 disease) and those who are on dialysis. One key issue is how to define cardiovascular events such as acute coronary syndrome and heart failure in patients with later stages of chronic kidney diseases, including end-stage renal disease, and whether the developed standardised definitions for cardiovascular endpoints7 are well suited for this population. For the diagnosis of myocardial infarction, the recommendation is to base thresholds for biomarker detection of myocardial infarction on 99th percentile values,7 and for cardiac biomarkers to be negative to fulfil the criteria7 for the diagnosis of unstable angina. However, baseline troponin concentrations are often elevated in patients with chronic kidney disease, while serial changes in dialysis patients with frequently and www.thelancet.com Vol 388 October 22, 2016
Comment
chronically elevated (even >99th percentile values) cardiac troponin have uncertain clinical implications and are difficult to interpret.8,9 Are specific thresholds— that take into consideration the stage of chronic kidney disease to assessing changes in troponin over time—needed to diagnose myocardial infarction and unstable angina in patients with more advanced chronic kidney disease and, if so, what should they be? Also, what criteria should be used to reliably distinguish a real heart failure admission from the unfortunate but common occurrence of transient fluid overload related to dry weight overestimation or nonadherence to diet in dialysis patients? Finally, what outcomes should we be focusing on in clinical trials in this population, particularly in trials of haemodialysis patients, in which predominant modes of cardiovascular death might differ from those observed in patients with chronic kidney disease but non-end-stage renal disease? Among patients with end-stage renal disease covered by Medicare, 37% of all deaths have been attributed to sudden death or cardiac arrhythmias and, in haemodialysis patients, unique factors, such as electrolyte shifts, contribute to these deaths.10,11 To target patients at higher risk for cardiovascular events for enrolment in clinical trials (prognostic enrichment) improves the ability to detect a treatment benefit in cardiovascular outcome trials, if such a benefit exists. Unfortunately, methods to identify patients with advanced chronic kidney disease who are likely to have adverse cardiovascular outcomes are inadequate. Additionally, although patients with chronic kidney disease are at high risk for cardiovascular death, they also have high rates of other causes of death, including sepsis and cancer.12 Better risk models are needed to identify patients who are likely to have particular adverse cardiovascular outcomes of interest and unlikely to die from a non-cardiovascular cause. Optimal statistical strategies for addressing competing risks also need to be considered. An agenda for further research should be encouraged, with the aim of validating traditional and potentially non-traditional cardiovascular risk markers in this population, and validating markers or combinations of markers that can be used to identify subsets of patients who might be more or less likely to respond to particular types of interventions. Relating to this issue, clinical trials in patients with a reduced ejection fraction have often used New York Heart www.thelancet.com Vol 388 October 22, 2016
Association classification, plasma B-type natriuretic peptide concentrations, ejection fraction, and a history of admissions to hospital for heart failure within some timeframe relative to the start of the trial to identify patients who have the condition of interest and who are likely to have the outcome of interest during the course of the trial. Will an enrichment strategy based on these same variables be effective in heart failure trials in patients with stage 4 or 5 chronic kidney disease, or does the volume overload resulting from diminished renal function limit our ability to use these variables to enrich the trial population? How can we best use measures of calcification or uraemic burden to identify subpopulations that might be likely to respond to interventions aimed at particular pathways that might be unique to advanced chronic kidney disease, and what outcomes should trials of such interventions target? Existing data should be leveraged to answer these and other questions. It is widely recognised that the rates of cardiovascular morbidity and mortality seen in patients with advanced stages of chronic kidney diseases are unacceptable. It is high time for nephrologists, cardiologists, clinical trialists, statisticians, industry, and regulators to come together to develop a roadmap to address the barriers discussed, as well as others, to do trials in this population. *Patrick Rossignol, Bertram Pitt, Aliza Thompson, Faiez Zannad Inserm 1433, Centre d’Investigations Cliniques-Plurithématique, Université de Lorraine, CHU Nancy, 54500 France (PR, FZ); F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France (PR, FZ); Association Lorraine de Traitement de l’Insuffisance Rénale, Nancy, France (PR); University of Michigan School of Medicine, Ann Arbor, MI, USA (BP); and Division of Cardiovascular and Renal Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA (AT) [email protected] AT is an employee of the FDA. This Comment reflects the views of the authors and should not be construed to represent the FDA’s views or policies. AT declares no other competing interests. PR has received personal fees from CVRx, Novartis, Relypsa, AstraZeneca, Vifor Fresenius Medical Care Renal Pharma, and Stealth Peptides, and is co-founder of Cardiorenal, a private company aimed at developing a telemonitoring loop for heart failure, outside the submitted work. BP has received personal fees from Bayer, Merck, AstraZeneca, Takeda, Relypsa, scPharmaceuticals, KBP Pharmaceuticals, PharMain, Tricida, and daVinci Therapeutics. FZ has received personal fees from Janssen, Bayer, Pfizer, Novartis, Boston Scientific, Resmed, Amgen, CVRx, Quantum Genomics, AstraZeneca, Eli Lilly, Relypsa, ZS Pharma, and Takeda, and is co-founder of Cardiorenal. 1
2
Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, et al. Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet 2013; 382: 339–52. Ortiz A, Covic A, Fliser D, et al. Epidemiology, contributors to, and clinical trials of mortality risk in chronic kidney failure. Lancet 2014; 383: 1831–43.
1965
Comment
3
4
5
6
7
Konstantinidis I, Nadkarni GN, Yacoub R, et al. Representation of patients with kidney disease in trials of cardiovascular interventions: an updated systematic review. JAMA Intern Med 2016; 176: 121–24. Zannad F, Kessler M, Lehert P, et al. Prevention of cardiovascular events in end-stage renal disease: results of a randomized trial of fosinopril and implications for future studies. Kidney Int 2006; 70: 1318–24. Fellstrom BC, Jardine AG, Schmieder RE, et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med 2009; 360: 1395–407. Rossignol P, Cridlig J, Lehert P, Kessler M, Zannad F. Visit-to-visit blood pressure variability is a strong predictor of cardiovascular events in hemodialysis: insights from FOSIDIAL. Hypertension 2012; 60: 339–46. Hicks KA, Tcheng JE, Bozkurt B, et al. 2014 ACC/AHA key data elements and definitions for cardiovascular endpoint events in clinical trials: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop Cardiovascular Endpoints Data Standards). Circulation 2015; 132: 302–61.
8
9
10 11
12
Sandoval Y, Herzog CA, Love SA, et al. Prognostic value of serial changes in high-sensitivity cardiac troponin I and T over 3 months using reference change values in hemodialysis patients. Clin Chem 2016; 62: 631–38. Badiou S, Boudet A, Leray-Moragues H, et al. Monthly reference change value of cardiac troponin in hemodialysis patients as a useful tool for long-term cardiovascular management. Clin Biochem 2016; published online May 20. DOI:10.1016/j.clinbiochem.2016.05.015. Green D, Roberts PR, New DI, Kalra PA. Sudden cardiac death in hemodialysis patients: an in-depth review. Am J Kidney Dis 2011; 57: 921–29. United States Renal Data System. 2015 USRDS annual data report: epidemiology of kidney disease in the United States. Bethesda, MD, USA: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2015. Vanholder R, Fouque D, Glorieux G, et al. Clinical management of the uraemic syndrome in chronic kidney disease. Lancet Diabetes Endocrinol 2016; 4: 360–73.
Improving outcomes of dialysis patients by population health management—the Global Chief Medical Officer Initiative
Life in View/Science Photo Library
Renal replacement therapy (RRT) by dialysis is a lifesustaining treatment that globally enables almost 3 million patients with end-stage renal disease to survive while maintaining daily activities of living.1 Despite technical progress in dialysis machines and dialyser performance, better understanding of uraemic pathophysiology, improvement in dialysis tolerance, and better management of anaemia and other comorbidities, patients have a high burden of chronic illness with substantial morbidity and mortality. Appropriate care of patients with end-stage renal disease includes collection of fundamental dialysis metrics, as well as those associated with management of comorbid disorders. Dialysis allows for systematic collection of clinical data across different care settings. Analysis of these data has the potential for
1966
population health management by revealing opportunities to improve patients’ care and to reduce costs.2 Worldwide there are increasing demands for RRT services, regional shortages of skilled caregivers, and constraints on funding. Ensuring quality of care, value-based delivery (defined as outcomes and service relative to costs), and meeting costs for end-stage renal disease are an increasing concern.3–5 There is a need for integrated care management of patients with advanced renal disease to optimise transitions of care (eg, initiation of RRT, post-acute hospitalisation care management), develop cost-effective alternative therapies and care structures, increase renal transplantation rates, and reduce the costs associated with caring for patients. These issues have led to an initiative by the Chief Medical Officers (CMO) of dialysis organisations in the USA to improve the quality of dialysis care.5,6 And now the CMOs of dialysis service providers operating dialysis clinics on five continents (the USA, South America, Europe, Asia, Oceania)—covering more than two-thirds of renal care providers—are collaborating to share their clinical expertise to harmonise the various clinical data definitions used in end-stage renal disease quality management through the Global CMO Initiative. In addition to harmonisation of data definitions, the group is dedicated to improving care and outcomes for dialysis patients worldwide by identifying, sharing, and promoting implementation of known best clinical practices in their clinic networks. Those taking part in the Global CMO Initiative aim to identify, discuss, and promote best practices for data www.thelancet.com Vol 388 October 22, 2016