Redfors Björn, Ben-Yehuda Ori, Lin Sheng-Hsuan, Furer Ariel, Kirtane Ajay J, Witzenbichler Bernhard, Weisz Giora, Stuckey Thomas D, Maehara Akiko, Généreux Philippe, Giustino Gennaro, Rinaldi Michael J, Neumann Franz-Josef, Metzger D Christopher, Henry Timothy D, Cox David A, Duffy Peter L, Mazzaferri Ernest L, Ayele Girma Minalu, Mehran Roxana, Mintz Gary S, Stone Gregg W
Clinical Trials Center, Cardiovascular Research Foundation, New York, New York.
Clinical Trials Center, Cardiovascular Research Foundation, New York, New York; NewYork-Presbyterian Hospital/Columbia University Medical Center, New York, New York.
Am J Cardiol. 2017 Sep 15;120(6):917-923. doi: 10.1016/j.amjcard.2017.06.019. Epub 2017 Jun 28.
Patients at high risk of thrombotic events after percutaneous coronary intervention (PCI) may potentially benefit from intensified antiplatelet therapy. However, more potent antiplatelet therapy would be expected to only overcome risk that is mediated by high platelet reactivity (PR). We used mediation analysis to determine the contribution of residual PR to the 2-year risk of major adverse cardiac events (MACE; the composite of cardiac death, myocardial infarction, or stent thrombosis) associated with clinical risk factors after PCI with drug-eluting stents (DES) in 8,374 patients from the prospective, multicenter Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents (ADAPT-DES) registry. Residual PR on clopidogrel, as measured by the VerifyNow P2Y12 point-of-care assay, was included as a continuous linear mediator variable in Cox proportional hazards regression. Among 7 factors independently associated with 2-year MACE, residual PR partly mediated the effect of diabetes (13.4% attributable risk), anemia (22.9% attributable risk), and acute coronary syndromes (7.3% attributable risk). A PR-mediated effect inversely affected the MACE risk associated with smoking (10.4% attributable risk). The increased ischemic risk of chronic kidney disease, multivessel disease, and previous myocardial infarction were not mediated by residual PR. In conclusion, high residual PR mediates little or none of the increased 2-year MACE risk associated with baseline risk factors in patients treated with clopidogrel after successful PCI with DES. Intensifying antiplatelet therapy is therefore unlikely to substantially mitigate the excess ischemic risk from these variables.
经皮冠状动脉介入治疗（PCI）后有血栓形成事件高风险的患者可能会从强化抗血小板治疗中获益。然而，更强效的抗血小板治疗预计只能克服由高血小板反应性（PR）介导的风险。我们采用中介分析来确定在来自前瞻性多中心药物洗脱支架双重抗血小板治疗评估（ADAPT-DES）注册研究的8374例患者中，PCI植入药物洗脱支架（DES）后，残余PR对与临床风险因素相关的2年主要不良心脏事件（MACE；心脏死亡、心肌梗死或支架血栓形成的复合事件）风险的贡献。通过VerifyNow P2Y12即时检测法测量的氯吡格雷残余PR作为连续线性中介变量纳入Cox比例风险回归分析。在与2年MACE独立相关的7个因素中，残余PR部分介导了糖尿病（归因风险13.4%）、贫血（归因风险22.9%）和急性冠状动脉综合征（归因风险7.3%）的影响。PR介导的效应与吸烟相关的MACE风险呈负相关（归因风险10.4%）。慢性肾病、多支血管病变和既往心肌梗死增加的缺血风险未由残余PR介导。总之，在DES成功PCI后接受氯吡格雷治疗的患者中，高残余PR对与基线风险因素相关的2年MACE风险增加的介导作用很小或不存在。因此，强化抗血小板治疗不太可能显著减轻这些变量带来的额外缺血风险。
