Hedegaard Sofie S, Hvas Anne-Mette, Grove Erik L, Refsgaard Jens, Rocca Bianca, Daví Giovanni, Kristensen Steen D
Department of Cardiology, Aarhus University Hospital Skejby, Denmark.
Thromb Res. 2009 May;124(1):96-100. doi: 10.1016/j.thromres.2008.12.034. Epub 2009 Feb 11.
Aspirin reduces cardiovascular events in patients with coronary artery disease (CAD), but studies report a highly variable response to aspirin, often referred to as 'aspirin low-responsiveness'. We investigated whether 75 mg of daily non-enteric coated aspirin would completely inhibit the platelet cyclooxygenase-1 activity to a comparable extent in healthy individuals and stable CAD patients.
We assessed serum thromboxane B2 (S-TxB2), urinary 11-dehydro-TxB2 (U-TxM) and arachidonic acid-induced optical platelet aggregometry (OPA) in 44 CAD patients on aspirin and in 22 healthy individuals before and after aspirin. OPA was performed in duplicate for four consecutive days during aspirin treatment after one week of treatment. Compliance was optimized by face-to-face interviews and pill counting and confirmed by S-TxB(2) measurements.
Aspirin inhibited S-TxB2 >99% in healthy individuals (median 1.1 ng/mL, interquartile range (IQR) = 0.8;1.9 after aspirin) and in patients, S-TxB2 was reduced to a similar level (0.9 ng/mL (0.7;1.5)). Healthy individuals had a median U-TxM of 278.5 pg/mg creatinine (229.5;380.0) before aspirin and 68.5 pg/mg creatinine (59.0;99.7) on aspirin corresponding to an average 74% inhibition of the endogenous TxA2 biosynthesis. In patients median U-TxM was 67.5 pg/mg creatinine (54.0;85.5). Seven study participants (11%) were aspirin low-responders according to OPA, but none had S-TxB2 in the highest quartile.
Low-dose aspirin suppressed S-TxB(2) to comparable levels in CAD patients and healthy individuals. Despite an almost complete inhibition of S-TxB2, some participants were low-responders according to OPA. Thorough compliance control and use of thromboxane-specific assays are important when measuring platelet response to aspirin.
阿司匹林可降低冠心病（CAD）患者的心血管事件发生率，但研究报告称对阿司匹林的反应差异很大，常被称为“阿司匹林低反应性”。我们研究了每日75毫克的非肠溶阿司匹林是否能在健康个体和稳定型CAD患者中以相当的程度完全抑制血小板环氧化酶-1活性。
我们评估了44例服用阿司匹林的CAD患者和22例健康个体在服用阿司匹林前后的血清血栓素B2（S-TxB2）、尿11-脱氢血栓素B2（U-TxM）以及花生四烯酸诱导的光学血小板聚集测定（OPA）。在治疗一周后的阿司匹林治疗期间，连续四天重复进行OPA测定。通过面对面访谈和清点药片来优化依从性，并通过S-TxB2测量进行确认。
阿司匹林在健康个体中抑制S-TxB2>99%（中位数1.1纳克/毫升，四分位间距（IQR）=0.8；服用阿司匹林后为1.9），在患者中，S-TxB2降至相似水平（0.9纳克/毫升（0.7；1.5））。健康个体在服用阿司匹林前U-TxM的中位数为278.5皮克/毫克肌酐（229.5；380.0），服用阿司匹林后为68.5皮克/毫克肌酐（59.0；99.7），相当于内源性血栓素A2生物合成平均抑制74%。患者中U-TxM的中位数为67.5皮克/毫克肌酐（54.0；85.5）。根据OPA，7名研究参与者（11%）为阿司匹林低反应者，但无人的S-TxB2处于最高四分位数。
低剂量阿司匹林在CAD患者和健康个体中将S-TxB2抑制到相当水平。尽管S-TxB2几乎完全被抑制，但根据OPA，一些参与者为低反应者。在测量血小板对阿司匹林的反应时，全面的依从性控制和使用血栓素特异性检测很重要。
