A prediction of the renal and cardiovascular efficacy of aliskiren in ALTITUDE using short-term changes in multiple risk markers

European Journal of Preventive Cardiology, SAGE Publications, ISSN 2047-4873

Volume 21, 4, 2014

DOI:10.1177/2047487313481754, Dimensions: pub.1034772367, PMID: 23467676,



  1. (1) University Medical Center Groningen, grid.4494.d
  2. (2) University Medical Center Utrecht, grid.7692.a
  3. (3) Aarhus University, grid.7048.b, AU
  4. (4) University of Copenhagen, grid.5254.6, KU
  5. (5) Steno Diabetes Center, grid.419658.7, Capital Region
  6. (6) Holbæk Sygehus, grid.414289.2, Zealand Region
  7. (7) Umeå University, grid.12650.30
  8. (8) Gentofte Hospital, grid.411646.0, Capital Region








INTRODUCTION: We recently developed and validated in existing trials a novel algorithm (PRE score) to predict long-term drug efficacy based on short-term (month-6) drug-induced changes in multiple risk markers. To show the value of the PRE score for ongoing and planned clinical trials, we here report the predicted long-term cardio-renal efficacy of aliskiren in type 2 diabetes, which was investigated in the ALTITUDE trial, but unknown at the time this study was conducted. METHODS: We established the relation between multiple risk markers and cardio-renal endpoints (as defined in ALTITUDE) using a background database from past clinical trials. The short-term effect of aliskiren on multiple risk markers was taken from the AVOID trial. A PRE score was developed by multivariate Cox analysis in the background population and was then applied to the baseline and month-6 measurements of the aliskiren treatment arm of the AVOID trial to predict cardio-renal risk. The net risk difference at these time-points, after correction for placebo effects, was taken to indicate the estimated long-term cardio-renal risk change. RESULTS: Based on the PRE score, we predicted that aliskiren treatment in ALTITUDE would confer a relative risk change of -7.9% (95% CI -2.5 to -13.4) for the cardio-renal endpoint, a risk change of -5.1% (-1.2 to -9.0) for the CV endpoint and a non-significant risk change of -19.9% (-42.1 to +2.1) for the renal endpoint. CONCLUSIONS: PRE score estimations suggested that aliskiren has only a marginal additive protective effect on cardio-renal endpoints. These predictions were validated by the results of the ALTITUDE trial, confirming the potential of the PRE score to prospectively predict drug efficacy on cardio-renal outcomes.


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