Division of Cardiology, University of Colorado School of Medicine, Aurora, CO, USA.
Department of Veterans Affairs Eastern Colorado Healthcare System, Rocky Mountain, Regional VA Medical Center, Medicine Service (111), 1700 North Wheeling Street, Aurora, CO, 80045, USA.
Cardiovasc Diabetol. 2022 Apr 27;21(1):58. doi: 10.1186/s12933-022-01496-7.
Evidence to guide type 2 diabetes treatment individualization is limited. We evaluated heterogeneous treatment effects (HTE) of intensive glycemic control in type 2 diabetes patients on major adverse cardiovascular events (MACE) in the Action to Control Cardiovascular Risk in Diabetes Study (ACCORD) and the Veterans Affairs Diabetes Trial (VADT).
Causal forests machine learning analysis was performed using pooled individual data from two randomized trials (n = 12,042) to identify HTE of intensive versus standard glycemic control on MACE in patients with type 2 diabetes. We used variable prioritization from causal forests to build a summary decision tree and examined the risk difference of MACE between treatment arms in the resulting subgroups.
A summary decision tree used five variables (hemoglobin glycation index, estimated glomerular filtration rate, fasting glucose, age, and body mass index) to define eight subgroups in which risk differences of MACE ranged from - 5.1% (95% CI - 8.7, - 1.5) to 3.1% (95% CI 0.2, 6.0) (negative values represent lower MACE associated with intensive glycemic control). Intensive glycemic control was associated with lower MACE in pooled study data in subgroups with low (- 4.2% [95% CI - 8.1, - 1.0]), intermediate (- 5.1% [95% CI - 8.7, - 1.5]), and high (- 4.3% [95% CI - 7.7, - 1.0]) MACE rates with consistent directions of effect in ACCORD and VADT alone.
This data-driven analysis provides evidence supporting the diabetes treatment guideline recommendation of intensive glucose lowering in diabetes patients with low cardiovascular risk and additionally suggests potential benefits of intensive glycemic control in some individuals at higher cardiovascular risk.
指导 2 型糖尿病治疗个体化的证据有限。我们评估了强化血糖控制对 ACTION TO CONTROL CARDIOVASCULAR RISK IN DIABETES STUDY（ACCORD）和 Veterans Affairs Diabetes Trial（VADT）中 2 型糖尿病患者主要不良心血管事件（MACE）的异质性治疗效果（HTE）。
使用来自两项随机试验（n=12042）的汇总个体数据，通过因果森林机器学习分析，确定 2 型糖尿病患者强化与标准血糖控制对 MACE 的 HTE。我们使用因果森林的变量优先级构建了一个总结决策树，并在生成的子组中检查了治疗臂之间 MACE 的风险差异。
总结决策树使用五个变量（糖化血红蛋白指数、估计肾小球滤过率、空腹血糖、年龄和体重指数）来定义八个子组，其中 MACE 的风险差异范围从 -5.1%（95%CI -8.7，-1.5）到 3.1%（95%CI 0.2，6.0）（负值表示强化血糖控制与较低的 MACE 相关）。在 ACCORD 和 VADT 单独的子组中，强化血糖控制与 MACE 较低相关（低风险组 -4.2%[95%CI -8.1，-1.0]、中风险组 -5.1%[95%CI -8.7，-1.5]、高风险组 -4.3%[95%CI -7.7，-1.0]），且效果方向一致，这与汇集研究数据一致。
这项基于数据的分析提供了支持指南的证据，即对于心血管风险较低的糖尿病患者，建议进行强化血糖降低治疗，此外，对于心血管风险较高的一些个体，强化血糖控制可能具有潜在益处。
