From the Department of Vascular Medicine (J.v.d.L., F.L.J.V.), Julius Centre for Health Sciences and Primary Care (Y.v.d.G., D.E.G.), University Medical Centre Utrecht, Utrecht, The Netherlands; The George Institute for Global Health, University of Sydney, Sydney, Australia (M.W., S.Z., A.P.K., S.M., J.C.); NCRP for Cardiovascular and Metabolic Diseases, South African Medical Research Council and University of Cape Town, Cape Town, South Africa (A.P.K.); Centre for Research on Evidence Based Practice, Bond University, Robina, Queensland, Australia (P.G.); Centre Hospitalier de L'Université de Montréal, Montréal, Canada (P.H.); University of Oxford, Oxford, United Kingdom (S.M.); and Imperial College London, London, United Kingdom (N.P.).
Hypertension. 2015 Jan;65(1):115-21. doi: 10.1161/HYPERTENSIONAHA.114.04421. Epub 2014 Oct 13.
Blood pressure-lowering treatment reduces cardiovascular risk in patients with diabetes mellitus, but the effect varies between individuals. We sought to identify which patients benefit most from such treatment in a large clinical trial in type 2 diabetes mellitus. In Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) participants (n=11 140), we estimated the individual patient 5-year absolute risk of major adverse cardiovascular events with and without treatment by perindopril-indapamide (4/1.25 mg). The difference between treated and untreated risk is the estimated individual patient's absolute risk reduction (ARR). Predictions were based on a Cox proportional hazards model inclusive of demographic and clinical characteristics together with the observed relative treatment effect. The group-level effect of selectively treating patients with an estimated ARR above a range of decision thresholds was compared with treating everyone or those with a blood pressure >140/90 mm Hg using net benefit analysis. In ADVANCE, there was wide variation in treatment effects across individual patients. According to the algorithm, 43% of patients had a large predicted 5-year ARR of ≥1% (number-needed-to-treat [NNT5] ≤100) and 40% had an intermediate predicted ARR of 0.5% to 1% (NNT5=100-`200). The proportion of patients with a small ARR of ≤0.5% (NNT5≥200) was 17%. Provided that one is prepared to treat at most 200 patients for 5 years to prevent 1 adverse outcome, prediction-based treatment yielded the highest net benefit. In conclusion, a multivariable treatment algorithm can identify those individuals who benefit most from blood pressure-lowering therapy in terms of ARR of major adverse cardiovascular events and may be used to guide treatment decisions in individual patients with diabetes.
http://www.clinicaltrials.gov. Unique identifier: NCT00145925.
降压治疗可降低糖尿病患者的心血管风险，但个体间疗效存在差异。我们旨在通过大型 2 型糖尿病临床试验确定哪些患者能从降压治疗中最大获益。在糖尿病和血管疾病的行动：培哚普利吲达帕胺与氨氯地平控释片对照评估（ADVANCE）中，我们根据培哚普利吲达帕胺（4/1.25mg）估算了 11140 例患者的主要不良心血管事件的个体患者 5 年绝对风险，包括治疗和不治疗时的情况。治疗和未治疗风险的差异即为个体患者的绝对风险降低（ARR）。预测基于包括人口统计学和临床特征的 Cox 比例风险模型，以及观察到的治疗相对效果。通过净效益分析，比较了针对 ARR 预测值大于一系列决策阈值的患者选择性治疗与对所有患者或血压>140/90mmHg 的患者进行治疗的效果。在 ADVANCE 中，个体间的治疗效果存在广泛差异。根据该算法，43%的患者有≥1%的大预测 5 年 ARR（需要治疗数[NNT5]≤100），40%的患者有 0.5%至 1%的中等预测 ARR（NNT5=100-200）。ARR≤0.5%（NNT5≥200）的患者比例为 17%。假设最多愿意治疗 200 例患者 5 年以预防 1 例不良结局，则基于预测的治疗可产生最高的净效益。综上，多变量治疗算法可识别出从主要不良心血管事件的 ARR 获益最大的个体，并可用于指导个体糖尿病患者的治疗决策。
