Department of Cardiology, Aarhus University Hospital, Skejby, Denmark.
Heart. 2010 Mar;96(5):368-71. doi: 10.1136/hrt.2009.181107. Epub 2009 Nov 11.
To evaluate the effect of proton pump inhibitors (PPIs) on the platelet response to aspirin in patients with coronary artery disease (CAD).
Case-control study.
418 stable patients with CAD, 54 of whom were treated with PPIs. All patients were treated with non-enteric coated aspirin 75 mg/day and received no other antithrombotic drugs.
Platelet aggregation was measured by Multiplate (Dynabyte, Munich, Germany) whole blood aggregometry induced by arachidonic acid 1.0 mmol/l and expressed as area under the aggregation curve (aggregation units*min). Platelet activation was assessed by soluble serum P-selectin. Compliance was confirmed by serum thromboxane B(2) levels.
The distribution of age, sex, body mass index, blood pressure, family history of ischaemic heart disease, smoking, diabetes and the number of previous ischaemic events did not differ between groups. All patients were compliant with aspirin treatment according to serum thromboxane B(2) levels. Platelet aggregation (median 180 (interquartile range 119-312) vs 152 (84-226) aggregation units*min, p=0.003) and soluble serum P-selectin levels (88.5 (65.2-105.8) vs 75.4 (60.0-91.5) ng/ml, p=0.005) were significantly higher in patients treated with PPIs. Furthermore, these patients had significantly higher serum thromboxane B(2) levels (geometric mean 1.29 (95% CI 0.96 to 1.72) vs 0.92 (0.84 to 1.01) ng/ml, p=0.01).
Patients with CAD treated with PPIs had a reduced platelet response to aspirin, as shown by increased residual platelet aggregation and platelet activation, compared with patients with CAD not taking PPIs. Concomitant use of aspirin and PPIs might reduce the cardiovascular protection by aspirin.
评估质子泵抑制剂 (PPI) 对冠心病 (CAD) 患者阿司匹林血小板反应的影响。
病例对照研究。
418 例稳定型 CAD 患者,其中 54 例接受 PPI 治疗。所有患者均接受非肠溶阿司匹林 75mg/天治疗,未使用其他抗血栓药物。
采用 Dynabyte 公司的 Multiplate 全血聚集仪检测花生四烯酸 1.0mmol/L 诱导的血小板聚集,并用聚集曲线下面积(聚集单位*min)表示。通过可溶性血清 P-选择素评估血小板活化。通过血清血栓素 B2 水平确认依从性。
两组间年龄、性别、体重指数、血压、缺血性心脏病家族史、吸烟、糖尿病和既往缺血事件数的分布无差异。所有患者均根据血清血栓素 B2 水平对阿司匹林治疗有良好的依从性。与未服用 PPI 的 CAD 患者相比,服用 PPI 的患者血小板聚集(中位数 180(四分位距 119-312)与 152(84-226)聚集单位*min,p=0.003)和可溶性血清 P-选择素水平(88.5(65.2-105.8)与 75.4(60.0-91.5)ng/ml,p=0.005)显著升高。此外,这些患者的血清血栓素 B2 水平也显著升高(几何均数 1.29(95%可信区间 0.96 至 1.72)与 0.92(0.84 至 1.01)ng/ml,p=0.01)。
与未服用 PPI 的 CAD 患者相比,服用 PPI 的 CAD 患者阿司匹林的血小板反应降低,表现为残余血小板聚集和血小板活化增加。阿司匹林与 PPI 同时使用可能会降低阿司匹林的心血管保护作用。