H J L Heerspink1, T Ninomiya2, F Persson3, B M Brenner4, P Brunel5, N Chaturvedi6, A S Desai7, S M Haffner8, J J V Mcmurray9, S D Solomon7, M A Pfeffer7, H-H Parving10, D de Zeeuw1. 1. Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 2. Division of Research Management, Center for Cohort Studies Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 3. Steno Diabetes Centre, Gentofte, Denmark. 4. Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 5. Novartis Pharma AB, Global Medical Affairs, Basel, Switzerland. 6. Institute of Cardiovascular Sciences, University College London, London, UK. 7. Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. 8. Department of Medicine and Clinical Epidemiology, University of Texas Health Science Center, San Antonio, TX, USA. 9. British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, UK. 10. Department of Medical Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Abstract
AIMS: To investigate whether the degree of albuminuria reduction observed in the ALTITUDE trial is associated with renal and cardiovascular protection, and secondly, whether the reduction in albuminuria was too small to afford clinical benefit. METHODS: In a post hoc analysis of the ALTITUDE trial in 8561 patients with type 2 diabetes and chronic kidney disease or cardiovascular disease we examined the effect of albuminuria changes at 6 months on renal and cardiovascular outcomes using Cox proportional hazard regression. RESULTS: The median change in albuminuria in the first 6 months in the aliskiren arm of the trial was -12% (25th to 75th percentile: -48.7_to_ +41.9%) and 0.0% (25th to 75th percentile: -40.2_to_55%) in the placebo arm. Changes in albuminuria in the first 6 months were linearly associated with renal and cardiovascular endpoints: a >30% reduction in albuminuria in the first 6 months was associated with a 62% reduction in renal risk and a 25% reduction in cardiovascular risk compared with an increase in albuminuria. The association between changes at 6 months in albuminuria and renal or cardiovascular endpoints was similar in the two treatment groups (p for interaction >0.1 for both endpoints). CONCLUSIONS: The addition of aliskiren to angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy resulted in albuminuria changes that were associated with renal and cardiovascular risk changes. This did not translate into renal or cardiovascular protection because the overall reduction in albuminuria in the aliskiren arm was too small and nearly similar to that in the placebo arm.
RCT Entities:
AIMS: To investigate whether the degree of albuminuria reduction observed in the ALTITUDE trial is associated with renal and cardiovascular protection, and secondly, whether the reduction in albuminuria was too small to afford clinical benefit. METHODS: In a post hoc analysis of the ALTITUDE trial in 8561 patients with type 2 diabetes and chronic kidney disease or cardiovascular disease we examined the effect of albuminuria changes at 6 months on renal and cardiovascular outcomes using Cox proportional hazard regression. RESULTS: The median change in albuminuria in the first 6 months in the aliskiren arm of the trial was -12% (25th to 75th percentile: -48.7_to_ +41.9%) and 0.0% (25th to 75th percentile: -40.2_to_55%) in the placebo arm. Changes in albuminuria in the first 6 months were linearly associated with renal and cardiovascular endpoints: a >30% reduction in albuminuria in the first 6 months was associated with a 62% reduction in renal risk and a 25% reduction in cardiovascular risk compared with an increase in albuminuria. The association between changes at 6 months in albuminuria and renal or cardiovascular endpoints was similar in the two treatment groups (p for interaction >0.1 for both endpoints). CONCLUSIONS: The addition of aliskiren to angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy resulted in albuminuria changes that were associated with renal and cardiovascular risk changes. This did not translate into renal or cardiovascular protection because the overall reduction in albuminuria in the aliskiren arm was too small and nearly similar to that in the placebo arm.
Authors: Sergei Petrykiv; C David Sjöström; Peter J Greasley; John Xu; Frederik Persson; Hiddo J L Heerspink Journal: Clin J Am Soc Nephrol Date: 2017-03-16 Impact factor: 8.237
Authors: Hiddo J L Heerspink; Di Xie; George Bakris; Ricardo Correa-Rotter; Fan-Fan Hou; Dalane W Kitzman; Donald Kohan; Hirofumi Makino; John J V McMurray; Vlado Perkovic; Peter Rossing; Hans-Henrik Parving; Dick de Zeeuw Journal: J Am Soc Nephrol Date: 2021-09-22 Impact factor: 10.121
Authors: Megumi Oshima; Brendon L Neuen; JingWei Li; Vlado Perkovic; David M Charytan; Dick de Zeeuw; Robert Edwards; Tom Greene; Adeera Levin; Kenneth W Mahaffey; Luca De Nicola; Carol Pollock; Norman Rosenthal; David C Wheeler; Meg J Jardine; Hiddo J L Heerspink Journal: J Am Soc Nephrol Date: 2020-09-30 Impact factor: 10.121
Authors: Meaghan Lunney; Marinella Ruospo; Patrizia Natale; Robert R Quinn; Paul E Ronksley; Ioannis Konstantinidis; Suetonia C Palmer; Marcello Tonelli; Giovanni Fm Strippoli; Pietro Ravani Journal: Cochrane Database Syst Rev Date: 2020-02-27
Authors: Hiddo J L Heerspink; Dennis L Andress; George Bakris; John J Brennan; Ricardo Correa-Rotter; Jyotirmoy Dey; Fan Fan Hou; Dalane W Kitzman; Donald Kohan; Hirofumi Makino; John McMurray; Vlado Perkovic; Sheldon Tobe; Melissa Wigderson; Hans-Henrik Parving; Dick de Zeeuw Journal: Diabetes Obes Metab Date: 2018-03-09 Impact factor: 6.577