Abstract
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 language | English (US) |
|---|---|
| Pages (from-to) | 949-958 |
| Number of pages | 10 |
| Journal | Circulation |
| Volume | 143 |
| Issue number | 9 |
| DOIs | |
| State | Published - Mar 2 2021 |
Funding
Dr Patel is supported by the National Institutes of Health and National Center for Advancing Translational Sciences (grant KL2TR001424). Dr Ferreira receives modest consulting fees from Boehringer-Ingelheim. Dr Shah has received research grants from Actelion, AstraZeneca, Corvia, Novartis, and Pfizer and has received consulting fees from Abbott, Actelion, AstraZeneca, Amgen, Axon Therapeutics, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Cardiora, CVRx, Cytokinetics, Eisai, GSK, Ionis, Ironwood, Merck, MyoKardia, Novartis, Pfizer, Sanofi, Shifamed, Tenax, and United Therapeutics. Dr Vaduganathan is supported by the KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst (National Institutes of Health and National Center for Advancing Translational Sciences Award UL 1TR002541) and has served on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer AG, Boehringer Ingelheim, Cytokinetics, and Relypsa. Dr Solomon has received research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol-Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lone Star Heart, Mesoblast, MyoKardia, National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, Sanofi Pasteur, and Theracos and has consulted for Akros, Alnylam, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Cardior, Corvia, Cytokinetics, Gilead, GlaxoSmithKline, Ironwood, Merck, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, Cardiac Dimensions, and Tenaya. Dr Packer has consulted for AbbVie, Actavis, Akcea, Amgen, AstraZeneca, Boehringer Ingelheim, Cardiorentis, Daiichi San-kyo, Johnson & Johnson, NovoNordisk, Pfizer, Sanofi, Synthetic Biologics, and Theravance. Dr Zannad has received fees for serving on a steering committee from Janssen, Bayer, Boston Scientific, CVRx, and Boehringer Ingelheim; has received consulting fees from Amgen, Vifor Pharma–Fresenius, Cardior, Cereno Pharmaceutical, Applied Therapeutics, and Merck; and has received consulting fees and fees for serving on a steering committee from AstraZeneca and serving as founder of CardioVascular Clinical Trialists Forum. The remaining authors have nothing to disclose.
Keywords
- cardiovascular diseases
- clinical trial
- kidney diseases
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)
