Heart failure events in randomized controlled trials for adults receiving maintenance dialysis: a meta-epidemiologic study

David Collister; Lonnie Pyne; Arrti A Bhasin; Brendan Smyth; William Herrington; Meg Jardine; Patrick B Mark; Sunil Badve; Patrick Rossignol; Laura M Dember; Christoph Wanner; Justin Ezekowitz; P J Devereaux; Patrick Parfrey; Ron Gansevoort; Michael Walsh

doi:10.1093/ndt/gfae156

Heart failure events in randomized controlled trials for adults receiving maintenance dialysis: a meta-epidemiologic study

Nephrol Dial Transplant. 2024 Jul 10:gfae156. doi: 10.1093/ndt/gfae156. Online ahead of print.

Authors

David Collister^{1

2

3}, Lonnie Pyne^{4

5

2}, Arrti A Bhasin⁴, Brendan Smyth⁶, William Herrington⁷, Meg Jardine⁸, Patrick B Mark⁹, Sunil Badve^{10

11

12}, Patrick Rossignol^{13

14}, Laura M Dember¹⁵, Christoph Wanner¹⁶, Justin Ezekowitz^{17

3}, P J Devereaux^{4

18

2}, Patrick Parfrey¹⁹, Ron Gansevoort²⁰, Michael Walsh^{4

5

2}

Affiliations

¹ University of Alberta, Department of Medicine, Division of Nephrology, Edmonton, Canada.
² Population Health Research Institute, Hamilton, Canada.
³ Canadian Vigour Center, Edmonton, Canada.
⁴ McMaster University, Department of Health Research Methodology, Evidence & Impact, Hamilton, Canada.
⁵ McMaster University, Department of Medicine, Division of Nephrology, Hamilton, Canada.
⁶ Department of Renal Medicine, St George Hospital, Kogarah, Australia and NHMRC Clinical Trials Centre, University of Sydney, Camperdown, Australia.
⁷ MRC Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
⁸ NHMRC Clinical Trials Centre, University of Sydney, Camperdown, Australia; Department of Renal Medicine, Concord Repatriation General Hospital, Sydney, Australia.
⁹ School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK.
¹⁰ Department of Nephrology, St George Hospital, Sydney, NSW, Australia.
¹¹ Faculty of Medicine & Health, UNSW Sydney, NSW, Australia.
¹² Renal and Metabolic Division, The George Institute for Global Health, Sydney, NSW, Australia.
¹³ Université de Lorraine, Centre d'Investigations Cliniques- Plurithématique 14-33, Inserm U1116, CHRU Nancy, and F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France.
¹⁴ Medicine and Nephrology-dialysis departments, Princess Grace Hospital, and Monaco Private Hemodialysis Centre, Monaco, Monaco.
¹⁵ Renal-Electrolyte and Hypertension Division and Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
¹⁶ Department of Clinical Research and Epidemiology, DZHI and University hospital Würzburg, Germany.
¹⁷ University of Alberta, Department of Medicine, Division of Cardiology, Edmonton, Canada.
¹⁸ McMaster University, Department of Medicine, Divisions of Cardiology and Perioperative Medicine, Hamilton, Canada.
¹⁹ Division of Nephrology, Department of Medicine, Faculty of Medicine, Memorial University Newfoundland.
²⁰ Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

PMID: 38986509
DOI: 10.1093/ndt/gfae156

Abstract

Background and hypothesis: Heart failure is characterized as cardiac dysfunction resulting in elevated cardiac filling pressures with symptoms and signs of congestion. Distinguishing heart failure from other causes of similar presentations in patients with kidney failure is challenging but necessary, and is needed in randomized controlled trials (RCTs) to accurately estimate treatment effects. The objective of this study was to review heart failure events, their diagnostic criteria and adjudication in RCTs of patients with kidney failure treated with dialysis. We hypothesized that heart failure events, diagnostic criteria and adjudication were infrequently reported in RCTs in dialysis.

Methods: We conducted a meta-epidemiologic systematic review of RCTs from high impact medical, nephrology and cardiology journals from 2000 to 2020. RCTs were eligible if they enrolled adults receiving maintenance dialysis for kidney failure and evaluated any intervention. Results. Of 561 RCTs in patients receiving dialysis, 36 (6.4%) reported heart failure events as primary (10, 27.8%) or secondary (31, 86.1%) outcomes. 10 of the 36 (27.8%) RCTs provided heart failure event diagnostic criteria and 5 of these 10 (50%) adjudicated heart failure events. These 10 RCTs included event diagnostic criteria for heart failure or heart failure hospitalizations, and their criteria included dyspnea (5/10), edema (2/10), rales/crackles (4/10), chest x-ray pulmonary edema or vascular redistribution (4/10), treatment in an acute setting (6/10) and ultrafiltration or dialysis (4/10). No study explicitly distinguished heart failure from volume overload secondary to non-adherence or underdialysis.

Conclusion: Overall, we found that heart failure events are infrequently reported in RCTs in dialysis and are heterogeneously defined. Further research is required to develop standardized diagnostic criteria that are practical and meaningful to patients and clinicians.

Keywords: dialysis; event diagnostic criteria; heart failure; meta-epidemiology.