Development and Validation of a Prediction Rule for Benefit and Harm of Dual Antiplatelet Therapy Beyond 1 Year After Percutaneous Coronary Intervention.
Development and Validation of a Prediction Rule for Benefit and Harm of Dual Antiplatelet Therapy Beyond 1 Year After Percutaneous Coronary Intervention.
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DOI：
10.1001/jama.2016.3775
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发表时间：
2016-04-26
期刊：
影响因子：
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通讯作者：
DAPT Study Investigators
中科院分区：
文献类型：
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作者：
Yeh RW;Secemsky EA;Kereiakes DJ;Normand SL;Gershlick AH;Cohen DJ;Spertus JA;Steg PG;Cutlip DE;Rinaldi MJ;Camenzind E;Wijns W;Apruzzese PK;Song Y;Massaro JM;Mauri L;DAPT Study Investigators
经皮冠状动脉介入治疗(PCI)后的双重抗血小板治疗减少了缺血，但增加了出血。开发一种临床决策工具，以确定持续使用硫代吡啶一年以上的患者有望获得的益处与危害。从DAPT研究数据中，得出了一个预测规则，将患者分组，以区分介入治疗后12-30个月的缺血和出血风险。Endeavor与Cypher支架置入术(PROTECT)试验通过引导重新抽样进行内部验证，并在患者内部进行与患者相关的结果验证。衍生组：来自11个国家的11648名随机DAPT研究患者(2009年8月至2014年5月)。验证组：来自36个国家的8709名随机保护试验患者(2007年6月至2014年7月)。12个月的开放标签硫吡啶加阿司匹林；18个月的随机继续硫吡啶加阿司匹林与安慰剂加阿司匹林。术后12-30个月出现缺血(支架血栓形成或心肌梗死[MI])和出血(中度/重度)。在衍生人群(平均年龄61.3岁，女性25.2%)中，348例(3.0%)发生缺血，215例(1.8%)发生出血。预测缺血和出血的派生队列模型的c统计量分别为0.70和0.68。预测规则为：首次出现心肌梗死、既往有心肌梗死或经皮冠状动脉介入治疗、糖尿病、支架直径<3 mm、吸烟和紫杉醇洗脱支架各得1分；充血性心力衰竭/低射血分数和静脉移植介入史各得2分；−为65岁或75岁各得1分；−为≥75岁各得2分。对于高分(≥2，n=5 917)的患者，持续服用硫代吡啶(与安慰剂相比)与减少缺血事件相关(2.7%对5.7%，风险差异[RD]−3.0%，95%CI−4.1%对−2.0%，p<；0.001)，与低分(<；2，n=5731，1.7%对2.3%，RD−0.7%，95%CI−1.4%至0.09%，p=0.07，交互作用p<；0.001)。相反，与低分数≥2(3.0%vs.1.4%，RD 1.5%，95%CI 0.8%至2.3%，p<；0.001；交互作用p=0.02)相比，继续服用硫代吡啶的患者出血增加较少(1.8%vs.1.4%，RD 0.4%，95%CI−0.3%至1.0%，p=0.26)。继续服用硫代吡啶的死亡率为2.1%，服用安慰剂的死亡率为2.1%(p=0.99)，而≥评分为1.7%，服用安慰剂的死亡率为0.9%(p=0.02，交互作用p=0.14-无统计学意义)。在验证队列(平均年龄62岁；2,061名女性(23.7%))中，发生缺血365例(4.2%)和出血171例(2.0%)，c统计量为0.64用于缺血模型和0.64用于出血。在该队列中，高评分患者的缺血事件增加(1.5%比0.7%，RD 0.73%，95%CI 0.23%比1.23%，P=0.002)，而出血量无显著差异(0.4%比0.5%，RD−0.16%，95%CI−0.46%比0.13%，P=0.31)。在经皮冠状动脉介入治疗一年后未发生重大出血或缺血事件的患者中，评估缺血和出血风险的预测规则在推导和验证队列中显示出适度的准确性。这一规则需要进一步的前瞻性评估，以评估对患者护理的潜在影响，以及在其他队列中的验证。ClinicalTrials.gov编号NCT00977938。
Dual antiplatelet therapy after percutaneous coronary intervention (PCI) reduces ischemia at the expense of increased bleeding. To develop a clinical decision tool to identify patients expected to derive benefit vs. harm from continuing thienopyridine beyond one year after PCI. From DAPT Study data, a prediction rule was derived stratifying patients into groups to distinguish ischemic and bleeding risk 12–30 months after PCI. Validation was internal via bootstrap resampling and external within the Patient Related OuTcomes with Endeavor versus Cypher stenting (PROTECT) trial. Derivation group: 11,648 randomized DAPT Study patients from 11 countries (August 2009–May 2014). Validation group: 8,709 randomized PROTECT trial patients from 36 countries (June 2007–July 2014). 12 months open-label thienopyridine plus aspirin; 18 months randomized continued thienopyridine plus aspirin vs. placebo plus aspirin. Ischemia (stent thrombosis or myocardial infarction [MI]) and bleeding (GUSTO moderate/severe) 12–30 months after PCI. Among the derivation population (mean age 61.3 years, 25.2% female), ischemia occurred in 348 (3.0%) and bleeding in 215 (1.8%). Derivation cohort models predicting ischemia and bleeding had c-statistics of 0.70 and 0.68, respectively. The prediction rule assigned 1 point each for MI at presentation, prior MI or PCI, diabetes, stent diameter <3 mm, smoking, and paclitaxel-eluting stent; 2 points each for history of congestive heart failure/low ejection fraction and vein graft intervention; −1 point for age 65–<75; and −2 points for age ≥ 75. For patients with high scores (≥ 2, n=5917), continued thienopyridine (vs. placebo) was associated with reduced ischemic events (2.7% vs. 5.7%, risk difference [RD] −3.0%, 95% CI −4.1% to −2.0%, p<0.001), compared to those with low scores (<2, n=5731, 1.7% vs. 2.3%, RD −0.7%, 95% CI −1.4% to 0.09%, p=0.07, interaction p< 0.001). Conversely, continued thienopyridine was associated with smaller increases in bleeding among scores ≥2 (1.8% vs. 1.4%, RD 0.4%, 95% CI −0.3% to 1.0%, p=0.26) compared with low scores <2 (3.0% vs. 1.4%, RD 1.5%, 95% CI 0.8% to 2.3%, p<0.001; interaction p=0.02). Mortality rates were 2.1% for continued thienopyridine vs. 2.1% for placebo (p=0.99) for scores ≥2, compared to 1.7% vs. 0.9%, respectively (p=0.02, interaction p=0.14 – non-significant) for scores <2. Among the validation cohort (mean age 62 years; 2,061 (23.7%) women), ischemia occurred in 365 (4.2%) and bleeding in 171 (2.0%), with c statistic 0.64 for ischemia model and 0.64 for bleeding. In this cohort, high score patients had increased ischemic events (1.5% vs. 0.7%, RD 0.73%, 95% CI 0.23% to 1.23%, p=0.002), and no significant difference in bleeding (0.4% vs. 0.5%, RD −0.16%, 95% CI −0.46% to 0.13%, p=0.31). Among patients not sustaining major bleeding or ischemic events one year after PCI, a prediction rule assessing ischemic and bleeding risks showed modest accuracy in derivation and validation cohorts. This rule requires further prospective evaluation to assess potential effects on patient care, as well as validation in other cohorts. ClinicalTrials.gov number NCT00977938.