Challenges of Cardio-Kidney Composite Outcomes in Large-Scale Clinical Trials

Ravi B. Patel, Jozine M. Ter Maaten, João Pedro Ferreira, Finnian R. McCausland, Sanjiv J. Shah, Patrick Rossignol, Scott D. Solomon, Muthiah Vaduganathan, Milton Packer, Aliza Thompson, Norman Stockbridge, Faiez Zannad*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Patients with chronic cardiovascular or metabolic diseases, including diabetes, hypertension, obesity, and heart failure, often have comorbid kidney disease. Long-term outcomes are worse in the setting of both cardiac and kidney disease compared with either disease in isolation. In addition, the clinical presentations of certain acute cardiovascular events (such as heart failure) and worsening kidney function overlap and may be challenging to distinguish. Recently, certain novel treatments have demonstrated beneficial effects on both cardiac and kidney outcomes. Sodium-glucose cotransporter-2 inhibitors have exhibited concordant risk reduction and clinically important benefits in chronic kidney disease with and without diabetes, diabetes and established cardiovascular disease or multiple atherosclerotic vascular disease risk factors, and heart failure with reduced ejection fraction with and without diabetes. Primary trial results have revealed that sacubitril-valsartan therapy improves cardiovascular outcomes in patients with chronic heart failure with reduced ejection fraction and post hoc analyses suggest favorable kidney effects. A concordant pattern of kidney benefit with sacubitril-valsartan has also been observed in chronic heart failure with preserved ejection fraction. Given the complex interplay between cardiac and kidney disease and the possibility that treatments may show concordant cardio-kidney benefits, there has been recent interest in formally acknowledging, defining, and using composite cardio-kidney outcomes in future cardiovascular trials. This review describes potential challenges in use of such outcomes that should be considered and addressed before their incorporation into such trials.

Original languageEnglish (US)
Pages (from-to)949-958
Number of pages10
Issue number9
StatePublished - Mar 2 2021


  • cardiovascular diseases
  • clinical trial
  • kidney diseases

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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