Predicting the effect of fenofibrate on cardiovascular risk for individual patients with type 2 diabetes
Koopal, Charlotte; Visseren, Frank L.J.; Westerink, Jan; Van Der Graaf, Yolanda; Ginsberg, Henry N.; Keech, Anthony C.
(2018) Diabetes Care, volume 41, issue 6, pp. 1244 - 1250
(Article)
Abstract
OBJECTIVE In clinical trials, treatment with fenofibrate did not reduce the incidence of major cardiovascular events (MCVE) in patients with type 2 diabetes mellitus (T2DM). However, treatment effects reported by trials comprise patientswho respond poorly and patients who respond well to fenofibrate. Our aim was to use statistical modeling to
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estimate the expected treatment effect of fenofibrate for individual patients with T2DM. RESEARCH DESIGN AND METHODS To estimate individual risk, the FIELD risk model, with 5-year MCVE as primary outcome, was externally validated in T2DM patients from ACCORD and the SMART observational cohort. Fenofibrate treatment effect was estimated in 17,142 T2DM patients from FIELD, ACCORD, and SMART. Individual treatment effect, expressed as absolute risk reduction (ARR), is the difference between treated and untreatedMCVE risk. Results were stratified for patients with and without dyslipidemia (i.e., high triglycerides and low LDL cholesterol). RESULTS External validation of the FIELD risk model showed good calibration and moderate discrimination in ACCORD (C-statistic 0.67 [95% CI 0.65-0.69]) and SMART (C-statistic 0.66 [95% CI 0.63-0.69]).Median 5-yearMCVE risk in all three studies combined was 6.7% (interquartile range [IQR] 4.0-11.7) in patients without (N = 13,224) and 9.4% (IQR 5.4-16.1%) in patientswith (N= 3,918) dyslipidemia. Themedian ARRwas 2.15% (IQR 1.23-3.68) in patients with dyslipidemia, corresponding with a number needed to treat (NNT) of 47, and 0.22% (IQR 0.13-0.38) in patients without dyslipidemia (NNT 455). CONCLUSIONS In individual patients with T2DM, there is a wide range of absolute treatment effect of fenofibrate, and overall the fenofibrate treatment effect was larger in patients with dyslipidemia. The method of individualized treatment effect prediction of fenofibrate onMCVE risk reduction in T2DMcan be used to guide clinical decision making.
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Keywords: Internal Medicine, Endocrinology, Diabetes and Metabolism, Advanced and Specialised Nursing
ISSN: 0149-5992
Publisher: American Diabetes Association Inc.
Note: Funding Information: 1Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands 2Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands 3Irving Institute for Clinical and Translational Research, Columbia College of Physicians and Surgeons, New York, NY 4National Health and Medical Research Council Clinical Trials Centre, Sydney Medical School, University of Sydney, Sydney, Australia Corresponding author: Frank L.J. Visseren, f.l.j .visseren@umcutrecht.nl. Funding Information: knowledge the contribution of Rachel O’Connell, statistician at the National Health and Medical Research Council Clinical Trials Centre. Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. C.K. researched data and wrote the manuscript. F.L.J.V. contributed to discussion and reviewed and edited the manuscript. J.W. reviewed and edited the manuscript. Y.v.d.G. contributed to the discussion and reviewed and edited the manuscript. H.N.G. reviewed and edited the manuscript. A.C.K. researched data, contributed to the discussion, and reviewed and edited the manuscript. F.L.J.V. istheguarantorofthisworkand,assuch,hadfull access to all the data in the study and takes responsibilityfortheintegrityofthedataandthe accuracy of the data analysis. Publisher Copyright: © 2018 by the American Diabetes Association.
(Peer reviewed)