3rd Department of Cardiology, Silesian Center for Heart Disease, Medical University of Silesia, Zabrze, Poland.
Eur Cytokine Netw. 2010 Dec;21(4):257-63. doi: 10.1684/ecn.2010.0213. Epub 2010 Nov 18.
Dual antiplatelet therapy (aspirin plus clopidogrel) is recommended in patients undergoing percutaneous coronary intervention (PCI). Treatment with proton pump inhibitors (PPIs) decreases bleeding rate. Alarming reports have been made that PPIs may decrease the antiplatelet activity of clopidogrel. We sought to determine whether levels of interleukin-6 (IL-6) and transforming growth factor-β1 (TGF-β1) might help distinguish individuals at risk for adverse events.
Thirty-eight patients on aspirin and clopidogrel were enrolled and divided into two groups: group 1 [patients receiving omeprazole (n = 18)] and group 2 [patients not receiving omeprazole (n = 20)]. Patients underwent PCI and were scheduled for twelve-month clinical follow-up. The major, adverse cardiac and cerebrovascular events (MACCE) include death, re-hospitalization for acute coronary syndromes, and stroke.
Median concentrations of IL-6 were higher in group 1 at 4.7 pg/mL, in comparison with group 2, 1.65 pg/mL (p = 0.003). Median concentrations of TGF-β1 were similar in both groups (p = 0.5). Patients in group 1 had a significantly higher leukocyte count [103/mm3] (median 7.5 vs 6.5; p = 0.04). There were no deaths during follow-up. The incidence of myocardial infarction was higher in group 1 (33.4% vs 5.0%; p = 0.03). MACCE at twelve months were more frequent in group 1 (55.6% vs 20.0%; p = 0.02). The cut-off value to predict MACCEs for IL-6 was > 3.6 pg/mL (sensitivity 64%, specificity 88%, positive predictive value 75%, negative predictive value 81%).
We show here that concomitant omeprazole use is associated with an increased inflammatory reaction. Drug interactions may reduce the anti-inflammatory effect of clopidogrel. This mechanism maybe responsible for an increased risk of non-fatal, cardiovascular events, following stent placement.
双重抗血小板治疗（阿司匹林加氯吡格雷）被推荐用于经皮冠状动脉介入治疗（PCI）的患者。质子泵抑制剂（PPIs）的治疗可降低出血率。令人震惊的报告表明，PPIs 可能会降低氯吡格雷的抗血小板活性。我们试图确定白细胞介素-6（IL-6）和转化生长因子-β1（TGF-β1）的水平是否有助于区分发生不良事件的风险个体。
共纳入 38 名接受阿司匹林和氯吡格雷治疗的患者，并将其分为两组：第 1 组[接受奥美拉唑治疗的患者（n=18）]和第 2 组[未接受奥美拉唑治疗的患者（n=20）]。患者接受 PCI 治疗，并计划进行为期 12 个月的临床随访。主要不良心脏和脑血管事件（MACCE）包括死亡、因急性冠状动脉综合征再次住院和中风。
第 1 组的 IL-6 中位数浓度为 4.7 pg/mL，而第 2 组为 1.65 pg/mL（p=0.003）。两组 TGF-β1 的中位数浓度相似（p=0.5）。第 1 组的白细胞计数[103/mm3]明显较高（中位数 7.5 与 6.5；p=0.04）。随访期间无死亡。第 1 组心肌梗死的发生率较高（33.4%与 5.0%；p=0.03）。第 1 组 12 个月时 MACCE 更频繁（55.6%与 20.0%；p=0.02）。IL-6 预测 MACCE 的截断值>3.6 pg/mL（敏感性 64%，特异性 88%，阳性预测值 75%，阴性预测值 81%）。
我们在此表明，同时使用奥美拉唑与炎症反应增加有关。药物相互作用可能会降低氯吡格雷的抗炎作用。这种机制可能是支架置入后发生非致命性心血管事件风险增加的原因。
