Woźniak Sebastian, Woźniak Karolina, Hryniewiecki Tomasz, Kruk Mariusz, Różański Jacek, Kuśmierczyk Mariusz
Department of Cardiac Surgery and Transplantology, Institute of Cardiology in Warsaw, Warsaw, Poland.
Department of Clinical Biochemistry and Pharmacology, Institute of Cardiology in Warsaw, Warsaw, Poland.
Kardiochir Torakochirurgia Pol. 2016 Mar;13(1):3-9. doi: 10.5114/kitp.2016.58957. Epub 2016 Mar 30.
Postoperative bleeding is one of the most serious complications of cardiac surgery and requires transfusion of blood or blood products. Acetylsalicylic acid (ASA) and clopidogrel (CLO) are the two most commonly used antiplatelet agents; when used in combination (i.e., as dual antiplatelet therapy [DAPT]), they exert a synergistic effect. Dual antiplatelet therapy, however, significantly increases the risk of postoperative bleeding. The effect of antiplatelet therapy can be monitored by platelet aggregation testing. One of the most commonly methods used for assessing platelet reactivity is multiple electrode aggregometry (MEA) which can be performed with the use of Multiplate analyzer. Although the method has long been used in interventional cardiology to assess the effect of antiplatelet therapy, it is not available at cardiac surgery departments as a standard diagnostic procedure. The aim of the study was to establish the frequency of bleeding complications following coronary artery bypass graft (CABG) surgery in patients on single antiplatelet therapy (SAPT) and patients on DAPT and to determine the usefulness of routine measurement of platelet responsiveness before CABG surgery in patients receiving antiplatelet therapy.
A consecutive cohort of 200 patients referred for elective surgical treatment of stable coronary artery disease was enrolled (100 consecutive patients on SAPT [ASA 75 mg/day] and 100 consecutive patients on DAPT [ASA 75 mg/day + CLO 75 mg/day]). All subjects continued their antiplatelet therapy until the day before surgery. For each subject, platelet aggregation testing in the form of an ASPI test and an ADP test was performed on the Multiplate analyzer. Each subject underwent coronary artery bypass grafting surgery. For the primary and secondary endpoints in our study we adopted the definition provided in 'Standardised Bleeding Definitions for Cardiovascular Clinical Trials: A Consensus Report from the Bleeding Academic Research Consortium' ('Circulation', 2011) for BARC type 4 bleeding (i.e. CABG-related bleeding).
An ROC curve was constructed for the ASPI test and ADP test for a total of 200 patients. No significant correlations were demonstrated between the ASPI test results and either the primary endpoint or the secondary endpoints. A correlation was found between the ADP test results and the composite primary endpoint and each of the secondary endpoints. The primary endpoint of major postoperative bleeding occurred in 16 subjects. From the ROC curve, we established the optimal cut-off value for the ADP test of 26 U at sensitivity of 72%, specificity of 69%, positive predictive value of 69.90%, and negative predictive value of 71.13%.
In patients on antiplatelet therapy, an ADP test result of < 26 U is strongly predictive of serious bleeding complications after CABG surgery. The MEA ADP test allows to identify the group of patients at an increased risk of postoperative bleeding.
术后出血是心脏手术最严重的并发症之一,需要输血或血液制品。乙酰水杨酸(ASA)和氯吡格雷(CLO)是两种最常用的抗血小板药物;联合使用时(即作为双联抗血小板治疗 [DAPT]),它们发挥协同作用。然而,双联抗血小板治疗会显著增加术后出血风险。抗血小板治疗的效果可通过血小板聚集试验监测。用于评估血小板反应性的最常用方法之一是多电极聚集测定法(MEA),可使用Multiplate分析仪进行检测。尽管该方法长期以来一直在介入心脏病学中用于评估抗血小板治疗的效果,但在心脏外科科室尚未作为标准诊断程序使用。本研究的目的是确定接受单联抗血小板治疗(SAPT)和双联抗血小板治疗的患者在冠状动脉旁路移植术(CABG)后出血并发症的发生率,并确定在接受抗血小板治疗的患者中,CABG手术前常规测量血小板反应性的实用性。
连续纳入200例因稳定型冠状动脉疾病接受择期手术治疗的患者(100例连续接受SAPT [ASA 75毫克/天]治疗的患者和100例连续接受DAPT [ASA 75毫克/天 + CLO 75毫克/天]治疗的患者)。所有受试者持续进行抗血小板治疗直至手术前一天。对每个受试者,在Multiplate分析仪上进行以ASA试验和ADP试验形式的血小板聚集试验。每个受试者均接受冠状动脉旁路移植手术。对于我们研究的主要和次要终点,我们采用了《心血管临床试验标准化出血定义:出血学术研究联盟的共识报告》(《循环》,2011年)中针对BARC 4型出血(即CABG相关出血)的定义。
为200例患者构建了ASA试验和ADP试验的ROC曲线。ASA试验结果与主要终点或次要终点之间均未显示出显著相关性。发现ADP试验结果与复合主要终点及每个次要终点之间存在相关性。主要术后出血的主要终点发生在16名受试者中。根据ROC曲线,我们确定ADP试验的最佳截断值为26 U,灵敏度为72%,特异性为69%,阳性预测值为69.90%,阴性预测值为71.13%。
在接受抗血小板治疗的患者中,ADP试验结果<26 U强烈预示CABG手术后会发生严重出血并发症。MEA ADP试验能够识别术后出血风险增加的患者群体。