Smink, P A4; Hoekman, J4; Grobbee, D E4; Eijkemans, M J C4; Parving, H-H5; Persson, F4; Ibsen, Helene4; Lindholm, L4; Wachtell, K6; de Zeeuw, D4; Heerspink, H J Lambers4
1 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet2 Graduate School of Health and Medical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet3 Section of Surgery and Internal Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet4 unknown5 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet6 Graduate School of Health and Medical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet
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.
European Journal of Preventive Cardiology, 2014, Vol 21, Issue 4, p. 434-441
Aged; Algorithms; Amides; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Biological Markers; Cardiovascular Diseases; Decision Support Techniques; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Drug Therapy, Combination; Female; Fumarates; Humans; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Renin-Angiotensin System; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome