van der Leeuw Joep, Oemrawsingh Rohit M, van der Graaf Yolanda, Brugts Jasper J, Deckers Jaap W, Bertrand Michel, Fox Kim, Ferrari Roberto, Remme Willem J, Simoons Maarten L, Boersma Eric, Visseren Frank L J
Department of Vascular Medicine, University Medical Centre Utrecht, The Netherlands.
Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands.
Int J Cardiol. 2015 Mar 1;182:194-9. doi: 10.1016/j.ijcard.2014.12.046. Epub 2014 Dec 23.
Angiotensin-converting-enzyme inhibition reduces the risk of cardiovascular events at a group level. Presumably, the absolute effect of treatment varies between individuals. We sought to develop multivariable prediction scores to estimate individual treatment effect of perindopril in patients with stable coronary artery disease (sCAD).
In EUROPA trial participants, we estimated the individual patient 5-year absolute risk reduction (ARR) of major adverse cardiovascular events(MACE) by perindopril. Predictions were based on a new Coxproportional-hazards model with clinical characteristics and an external risk score in combination with the observed relative risk reduction. Second, a genetic profile modifying the relative efficacy of perindopril was added. The individual patient ARR was defined as the difference in MACE risk with and without treatment. The group level impact of selectively treating patients with the largest predicted treatment effect was evaluated using net benefit analysis.
The risk score combining clinical and genetic characteristics estimated the 5-year absolute treatment effect to be absent or adverse in 27% of patients. On the other hand, the risk score estimated a small 5-year ARR of ≤2% (NNT5≥50) in 20% of patients, a modest ARR of 2-4% (NNT5 25-50) in 26%, and a large ARR of ≥4% (NNT5≤25) in 28%. The external risk score yielded similar predictions. Selective prediction-based treatment resulted in higher net benefit compared to treat everyone at any treatment threshold.
A prediction score combining clinical characteristics and genetic information can quantify the ARR of MACE by perindopril for individual patients with sCAD and may be used to guide treatment decisions.
ISRCTN37166280.
血管紧张素转换酶抑制在群体水平上可降低心血管事件风险。据推测，治疗的绝对效果在个体间存在差异。我们试图开发多变量预测评分，以估计培哚普利对稳定型冠状动脉疾病（sCAD）患者的个体治疗效果。
在EUROPA试验参与者中，我们估计了培哚普利使主要不良心血管事件（MACE）的个体患者5年绝对风险降低（ARR）。预测基于一个新的Cox比例风险模型，该模型结合临床特征和外部风险评分以及观察到的相对风险降低情况。其次，加入了一个改变培哚普利相对疗效的基因谱。个体患者ARR定义为接受治疗和未接受治疗时MACE风险的差值。使用净效益分析评估选择性治疗预测治疗效果最大的患者的群体水平影响。
结合临床和基因特征的风险评分估计，27%的患者5年绝对治疗效果不存在或为不良。另一方面，风险评分估计20%的患者5年ARR较小，≤2%（NNT5≥50）；26%的患者ARR中等，为2 - 4%（NNT5为25 - 50）；28%的患者ARR较大，≥4%（NNT5≤25）。外部风险评分得出类似的预测结果。与在任何治疗阈值下对所有患者进行治疗相比，基于预测的选择性治疗产生了更高的净效益。
结合临床特征和基因信息的预测评分可以量化培哚普利对个体sCAD患者MACE的ARR，并可用于指导治疗决策。
ISRCTN37166280。
