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Eur Heart J. 2019 Mar 14;40(11):880-886. doi: 10.1093/eurheartj/ehx209.

Cardiovascular outcome trials in patients with chronic kidney disease: challenges associated with selection of patients and endpoints.

Author information

1
Inserm, Centre d'Investigations Cliniques- 1433, and Inserm U1116; CHRU Nancy; Université de Lorraine; Association Lorraine pour le Traitement de l'Insuffisance Rénale, Institut lorrain du Cœur et des Vaisseaux Louis Mathieu, 4 rue du Morvan, Nancy, France.
2
F-CRIN INI-CRCT, Nancy, France.
3
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
4
Richard L. Roudebush Veterans Administration Medical Center, Indianapolis, IN, USA.
5
Fresenius Medical Care Deutschland and University of Montpellier, UFR Medicine, France.
6
Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
7
AP-HP, Hôpital Européen Georges Pompidou, Unité de Recherche Clinique and INSERM CIC 1418, Paris, France.
8
School of Public Health, The University of Sydney, New South Wales, Australia.
9
Centre for Kidney Research, The Children's Hospital at Westmead, New South Wales, Australia.
10
Preventive Medicine Section, Veterans Affairs Medical Center, Memphis, Tennessee, USA.
11
Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
12
Inserm U1018, Université Paris-Saclay, UVSQ, Université. Paris-Sud, Villejuif, France.
13
Relypsa, Inc., Redwood City, CA, USA.
14
AstraZeneca, Gaithersburg, MD, USA.
15
Dutch Medicines Evaluation Board, Utrecht, The Netherlands.
16
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
17
France Centre Hospitalier F.H. Manhès, Fleury-Merogis, France.
18
Ambroise Pare University Hospital, APHP, Paris-Ile-de France-Ouest University (UVSQ), and INSERM U1018, Team 5 Boulogne Billancourt, France.
19
U942 Inserm, Paris, France.
20
University Paris Diderot, Sorbonne Paris Cité, Paris, France.
21
APHP, Department of Anesthesia and Critical Care, Hôpitaux Universitaires Saint Louis-Lariboisière, Paris, France.
22
Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
23
National Heart, Lung, and Blood Institute, Bethesda, MD, USA.
24
Institute of Investigation and Hypertension Unit, Hospital 12 de Octubre, Department of Preventive Medicine and Public Health, Universidad Autonoma and School of Doctoral Studies and Research, Universidad Europea de Madrid, Madrid, Spain.
25
ACI Clinical, Bala Cynwyd, PA, USA.
26
Sarfez Pharmaceuticals, Inc., McLean, VA, USA.
27
ZS Pharma, San Mateo, CA, USA.
28
AstraZeneca, Gothenburg, Sweden.
29
Division of Cardiovascular and Renal Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
30
Campbell University College of Pharmacy and Health Sciences, NC, USA.
31
Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
32
McMaster University and Population Health Research Institute, Hamilton, Canada.
33
Division of Nephrology, Department of Internal Medicine 1, University Hospital Würzburg and Comprehensive Heart Failure Center, Würzburg, Germany.
34
Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
35
Hypertension, Kidney and Vascular Research Center and Division of Nephrology and Hypertension, Department of Medicine, Georgetown University, Washington, DC, USA.
36
Statistics Collaborative, Inc., Washington, District of Columbia, USA.
37
University of Michigan School of Medicine, Ann Arbor, MI, USA.

Abstract

Although cardiovascular disease is a major health burden for patients with chronic kidney disease, most cardiovascular outcome trials have excluded patients with advanced chronic kidney disease. Moreover, the major cardiovascular outcome trials that have been conducted in patients with end-stage renal disease have not demonstrated a treatment benefit. Thus, clinicians have limited evidence to guide the management of cardiovascular disease in patients with chronic kidney disease, particularly those on dialysis. Several factors contribute to both the paucity of trials and the apparent lack of observed treatment effect in completed studies. Challenges associated with conducting trials in this population include patient heterogeneity, complexity of renal pathophysiology and its interaction with cardiovascular disease, and competing risks for death. The Investigator Network Initiative Cardiovascular and Renal Clinical Trialists (INI-CRCT), an international organization of academic cardiovascular and renal clinical trialists, held a meeting of regulators and experts in nephrology, cardiology, and clinical trial methodology. The group identified several research priorities, summarized in this paper, that should be pursued to advance the field towards achieving improved cardiovascular outcomes for these patients. Cardiovascular and renal clinical trialists must partner to address the uncertainties in the field through collaborative research and design clinical trials that reflect the specific needs of the chronic and end-stage kidney disease populations, with the shared goal of generating robust evidence to guide the management of cardiovascular disease in patients with kidney disease.

KEYWORDS:

Cardiovascular diseases; Chronic kidney failure; Chronic renal insufficiency; Clinical trials as topic

PMID:
28431138
DOI:
10.1093/eurheartj/ehx209

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