Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, the Netherlands.
J Thromb Haemost. 2011 Oct;9(10):1892-901. doi: 10.1111/j.1538-7836.2011.04483.x.
The carriage of CYP2C19*2 and the use of proton-pump inhibitors (PPIs) and calcium-channel blockers (CCBs) has been associated with the diminished efficacy of clopidogrel. However, previous studies have only assessed the isolated impact of these risk factors for clopidogrel poor response.
The aim of the present study was to investigate the impact of the combined presence of three risk factors for clopidogrel poor response, that is, the use of CCBs, PPIs and the carriage of CYP2C19*2, on on-treatment platelet reactivity and the occurrence of atherothrombotic events in 725 patients on dual antiplatelet therapy undergoing elective coronary stenting.
In a prospective, follow-up study, on-treatment platelet reactivity was quantified using ADP-induced light transmittance aggregometry (LTA) and the VerifyNow P2Y12 assay. The clinical study endpoint was the composite of all-cause mortality, myocardial infarction, stent thrombosis and stroke at 1 year after stenting.
Patients with either one or more than one risk factor exhibited increased platelet reactivity (mean relative increase one risk factor: 11% and > 1 risk factor: 22%, respectively). Sixty-four events occurred during follow-up (8.8% of the study population). Patients with one risk factor for clopidogrel poor response did not have an increased risk of the composite endpoint. However, patients using both CCBs and PPIs and carriers of CYP2C19*2 who used CCBs had a statistically significant increased risk of the composite endpoint [hazard ratio(HR)(adj) 2.2 95% CI, 1.0-5.3, P = 0.044 and HR(adj) 3.3 95% CI, 1.1-9.8, P = 0.032, respectively].
The presence of more than one of the three investigated risk factors for clopidogrel poor response is associated with an increased risk of adverse cardiovascular events within 1 year after elective coronary stenting.
CYP2C19*2 携带、质子泵抑制剂（PPIs）和钙通道阻滞剂（CCBs）的使用与氯吡格雷疗效降低有关。然而，以前的研究仅评估了这些氯吡格雷反应不良的危险因素的单独影响。
本研究旨在探讨氯吡格雷反应不良的三种危险因素（即 CCBs 的使用、PPIs 和 CYP2C19*2 的携带）同时存在对 725 例接受择期冠状动脉支架置入术的双联抗血小板治疗患者的治疗中的血小板反应性和动脉粥样血栓事件发生的影响。
在一项前瞻性随访研究中，使用 ADP 诱导的光透射聚集测定法（LTA）和 VerifyNow P2Y12 测定法来量化治疗中的血小板反应性。临床研究终点是支架置入后 1 年时全因死亡率、心肌梗死、支架血栓形成和卒中的复合终点。
有一个或多个危险因素的患者表现出更高的血小板反应性（一个危险因素的平均相对增加：11%，> 1 个危险因素：22%）。随访期间发生了 64 例事件（研究人群的 8.8%）。氯吡格雷反应不良的一个危险因素的患者没有增加复合终点的风险。然而，同时使用 CCB 和 PPI 且携带 CYP2C19*2 的患者使用 CCB 时，复合终点的风险有统计学显著增加[风险比（HR）（调整）2.2，95%置信区间，1.0-5.3，P = 0.044 和 HR（调整）3.3，95%置信区间，1.1-9.8，P = 0.032，分别]。
三种研究的氯吡格雷反应不良的危险因素中存在两个或更多的危险因素与择期冠状动脉支架置入术后 1 年内不良心血管事件的风险增加相关。
