Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria.
Eur J Clin Invest. 2020 Nov;50(11):e13304. doi: 10.1111/eci.13304. Epub 2020 Sep 9.
To investigate the long-term clinical benefit of dual antiplatelet therapy with potent P2Y12 inhibitors compared to clopidogrel in patients with acute coronary syndrome (ACS).
In this prospective multicenter observational study, we enrolled 708 patients with ACS treated with clopidogrel (n = 137), ticagrelor (n = 260) or prasugrel (n = 311). Major adverse cardiac events (MACE; over 1 year) and long-term mortality (median: 5.6 years; interquartile range [IQR] 4.9-6.5 years) were assessed. Multiple electrode aggregometry (MEA) was used to measure adenosine diphosphate (ADP)- and arachidonic acid (AA)-induced platelet aggregation.
Type of P2Y12 inhibitor emerged as an independent predictor of long-term mortality and MACE: patients treated with potent platelet inhibitors prasugrel or ticagrelor were at lower risk for long-term mortality (adjusted hazard ratio [HR] = 0.44; 95% CI: 0.22-0.92; P = .028) or MACE (adjusted HR = 0.38; 95% CI: 0.20-0.73; P = .004) than those treated with clopidogrel independent from clinical risk factors. In contrast, the efficacy of clopidogrel decreased with increasing severity of ACS: platelet aggregation was 37% higher in patients with ST segment elevation myocardial infarction (STEMI) and 25% higher in patients with non-ST elevation myocardial infarction (non-STEMI) compared to patients with unstable angina (P = .039). Patients with diabetes achieved less potent ADP- and AA-induced platelet inhibition under clopidogrel, compared to patients without diabetes (P = .045; P = .030, respectively).
In the setting of ACS, treatment with ticagrelor or prasugrel reduced long-term mortality and 1-year MACE as compared to clopidogrel.
研究与氯吡格雷相比，强效 P2Y12 抑制剂双联抗血小板治疗在急性冠状动脉综合征（ACS）患者中的长期临床获益。
在这项前瞻性多中心观察性研究中，我们纳入了 708 例接受氯吡格雷（n=137）、替格瑞洛（n=260）或普拉格雷（n=311）治疗的 ACS 患者。评估主要不良心脏事件（MACE；超过 1 年）和长期死亡率（中位数：5.6 年；四分位距 [IQR]：4.9-6.5 年）。使用多电极聚集仪（MEA）测量二磷酸腺苷（ADP）和花生四烯酸（AA）诱导的血小板聚集。
P2Y12 抑制剂的类型是长期死亡率和 MACE 的独立预测因素：接受强效血小板抑制剂普拉格雷或替格瑞洛治疗的患者，长期死亡率（调整后的危险比 [HR]：0.44；95%可信区间：0.22-0.92；P=0.028）或 MACE（调整后的 HR：0.38；95%可信区间：0.20-0.73；P=0.004）的风险低于接受氯吡格雷治疗的患者，且独立于临床危险因素。相反，氯吡格雷的疗效随着 ACS 严重程度的增加而降低：ST 段抬高型心肌梗死（STEMI）患者的血小板聚集率比不稳定型心绞痛患者高 37%（P=0.039），非 ST 段抬高型心肌梗死（非-STEMI）患者的血小板聚集率比不稳定型心绞痛患者高 25%。与无糖尿病患者相比，糖尿病患者在接受氯吡格雷治疗时，ADP 和 AA 诱导的血小板抑制作用较弱（P=0.045；P=0.030）。
在 ACS 患者中，与氯吡格雷相比，替格瑞洛或普拉格雷治疗可降低长期死亡率和 1 年 MACE。
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