P4990Heterogeneity of treatment effects from an intensive lifestyle weight loss intervention on cardiovascular events in patients with type 2 diabetes: data from the Look AHEAD trial

作者：T. I. Vries, J. Dorresteijn, Y. Graaf, F. Visseren, J. Westerink · 发表于：European Heart Journal · 年份：2019 · DOI：10.1093/eurheartj/ehz746.0168 · 研究领域：Medicine

The Action for Health in Diabetes trial (Look AHEAD) randomized overweight and obese patients with type 2 diabetes to either an intensive lifestyle intervention (ILI) or diabetes support and education (DSE). The trial was stopped early for futility after a median follow-up of 9.6 years due to a lack of effect on cardiovascular disease outcomes, despite beneficial effects on metabolic control and cardiovascular risk factors. Subgroup analyses identified no subgroups based on baseline characteristics with a significant treatment effect. However, traditional simple subgroup analyses have several disadvantages compared to a multivariable risk-based approach to identify heterogeneity of treatment effects (HTE). To explore the possible presence of HTE of an ILI on the occurrence of major cardiovascular events (4-point MACE: nonfatal myocardial infarction, nonfatal stroke, hospitalization for angina, and death from cardiovascular causes) in overweight or obese patients with type 2 diabetes mellitus, and to identify patient characteristics associated with treatment. In 4,901 patients from Look AHEAD, a ridge penalized Cox regression model to predict treatment effect of ILI versus DSE on the risk of MACE was derived including all possible treatment-by-covariate interaction terms. Next, the ability of the model to predict HTE was confirmed by calculating hazard ratios (HR) and absolute risk change in quartiles of predicted treatment effect, thereby leaving randomization i...