Personalizing the Intensity of Blood Pressure Control: Modeling the Heterogeneity of Risks and Benefits From SPRINT (Systolic Blood Pressure Intervention Trial).
Personalizing the Intensity of Blood Pressure Control: Modeling the Heterogeneity of Risks and Benefits From SPRINT (Systolic Blood Pressure Intervention Trial).
复制标题
DOI：
10.1161/circoutcomes.117.003624
复制
发表时间：
2017-04
期刊：
影响因子：
--
通讯作者：
Spertus JA
中科院分区：
文献类型：
--
作者：
Patel KK;Arnold SV;Chan PS;Tang Y;Pokharel Y;Jones PG;Spertus JA
在SPRINT（收缩压干预试验）中，与随机分配到标准血压对照组（<140mmHg）的患者相比，接受强化血压控制（< 120mmHg）治疗的高血压和高危心血管患者的主要不良心血管事件（MACE）和死亡较少，但与治疗相关的严重不良事件（SAE）发生率较高。然而，由于治疗效果的异质性，对个体患者的益处或危害程度可能有所不同。利用SPRINT中9361名随机患者的患者水平数据，我们开发了预测MACE或死亡风险和治疗相关SAE的模型，以便根据每位患者的预期风险和强化与标准血压控制的获益，制定个性化的血压治疗目标。采用自举重新采样对模型进行内部验证，并对来自ACCORD-BP试验的4741例患者进行外部验证。在9361例SPRINT患者中，755例（8.1%）患者发生MACE或死亡事件，338例（3.6%）患者发生治疗相关SAE，随访时间中位数为3.3年。在衍生队列中，MACE/death和SAE模型的c统计量分别为0.72和0.70，在ACCORD中为0.69和0.65。MACE/死亡模型有10个变量，包括治疗与年龄、基线收缩压和舒张压的相互作用；SAE模型有8个变量，包括治疗与降压药物数量的相互作用。强化降压治疗与标准治疗相比，MACE/死亡风险平均降低2.2%±2.6%（个体患者风险降低20.7%至19.6%），SAEs风险平均升高2.2%±1.2%（个体患者伤害增加0.5%至15.8%）。为了将SPRINT的研究结果转化为临床实践，我们开发了预测模型，根据每个患者的预期风险和收益来调整血压控制的强度。这种方法应该进行前瞻性测试，以更好地让患者参与共同的医疗决策并改善结果。
In SPRINT (Systolic blood PRessure INtervention Trial), patients with hypertension and high cardiovascular risk treated with intensive blood pressure (BP) control (< 120mmHg) had fewer major adverse cardiovascular events (MACE) and deaths, but higher rates of treatment-related serious adverse events (SAE), than patients randomized to standard BP control (<140mmHg). However, the degree of benefit or harm for an individual patient could vary due to heterogeneity in treatment effect. Using patient-level data from 9361 randomized patients in SPRINT, we developed models to predict risk for MACE or death and treatment-related SAE to allow for individualized BP treatment goals based on each patient’s projected risk and benefit of intensive vs. standard BP control. Models were internally validated using bootstrap resampling and externally validated on 4741 patients from the ACCORD-BP trial. Among 9361 SPRINT patients, 755 (8.1%) patients had a MACE or death event and 338 (3.6%) had a treatment-related SAE over a median follow-up of 3.3 years. The MACE/death and the SAE model had c-statistics of 0.72 and 0.70 respectively in the derivation cohort and 0.69 and 0.65 in ACCORD. The MACE/death model had 10 variables including treatment interactions with age, baseline SBP and DBP and the SAE model had 8 variables including treatment interaction with number of BP medications. Intensive BP treatment was associated with a mean 2.2% ± 2.6% lower risk of MACE/death compared with standard treatment (range = 20.7% lower risk to 19.6% greater risk among individual patients) and a mean 2.2% ± 1.2% higher risk for SAEs (range = 0.5% to 15.8% more harm in individual patients). To translate the findings from SPRINT to clinical practice, we developed prediction models to tailor the intensity of BP control based on the projected risk and benefit for each unique patient. This approach should be prospectively tested to better engage patients in shared medical decision-making and to improve outcomes.