Takahashi Yasuo, Nishida Yayoi, Nakayama Tomohiro, Asai Satoshi
Cardiovasc Diabetol. 2013 Jun 14;12:87. doi: 10.1186/1475-2840-12-87.
Clopidogrel and aspirin are antiplatelet agents that are recommended to reduce the risk of recurrent stroke and other cardiovascular events. Combination therapy of clopidogrel and aspirin has been shown to increase the risk of hemorrhage, but the effects of the drugs on laboratory parameters have not been well studied in patients in routine clinical practice. Therefore, we evaluated and compared the effects of combination therapy with clopidogrel plus aspirin and aspirin monotherapy on laboratory parameters using a clinical database.
We used data from the Clinical Data Warehouse of Nihon University School of Medicine obtained between November 2004 and April 2011, to identify cohorts of new users (n = 159) of clopidogrel (75 mg/day) plus aspirin (100 mg/day) and new users (n = 834) of aspirin alone (100 mg/day). We used a multivariable regression model and regression adjustment with the propensity score to adjust for differences in baseline covariates between settings, and compare the mean changes in serum levels of creatinine, aspartate aminotransferase, alanine aminotransferase and hematological parameters, including hemoglobin level, hematocrit, and white blood cell (WBC), red blood cell and platelet counts up to two months after the start of study drug administration.
After adjustment, the reduction of WBC count in clopidogrel plus aspirin users was significantly greater than that in aspirin alone users. All other tests showed no statistically significant difference in the mean change from baseline to during the exposure period between clopidogrel plus aspirin users and aspirin alone users. The combination of clopidogrel and aspirin increased the risk of gastrointestinal bleeding compared with aspirin alone, with a relative risk ranging from 2.06 (95% CI, 1.02 to 4.13; p = 0.043) for the multivariate model and 2.61 (95% CI, 1.18 to 5.80; p = 0.0184) for propensity adjustment.
Our findings suggested that hematological adverse effects may be greater with combination therapy of clopidogrel plus aspirin than with aspirin monotherapy.
氯吡格雷和阿司匹林是抗血小板药物，推荐用于降低复发性中风及其他心血管事件的风险。氯吡格雷与阿司匹林联合治疗已显示会增加出血风险，但在常规临床实践中，这些药物对实验室参数的影响尚未得到充分研究。因此，我们利用临床数据库评估并比较了氯吡格雷联合阿司匹林与阿司匹林单药治疗对实验室参数的影响。
我们使用了日本大学医学院临床数据仓库在2004年11月至2011年4月期间获取的数据，确定了氯吡格雷（75毫克/天）加阿司匹林（100毫克/天）的新使用者队列（n = 159）和仅使用阿司匹林（100毫克/天）的新使用者队列（n = 834）。我们使用多变量回归模型并通过倾向评分进行回归调整，以校正不同组间基线协变量的差异，并比较研究药物给药开始后长达两个月内血清肌酐、天冬氨酸转氨酶、丙氨酸转氨酶水平以及血液学参数（包括血红蛋白水平、血细胞比容以及白细胞、红细胞和血小板计数）的平均变化。
调整后，氯吡格雷加阿司匹林使用者的白细胞计数降低幅度显著大于仅使用阿司匹林的使用者。所有其他检测显示，氯吡格雷加阿司匹林使用者与仅使用阿司匹林的使用者在从基线到暴露期的平均变化方面无统计学显著差异。与仅使用阿司匹林相比，氯吡格雷与阿司匹林联合使用增加了胃肠道出血风险，多变量模型的相对风险为2.06（95%可信区间，1.02至4.13；p = 0.043），倾向调整后的相对风险为2.61（95%可信区间，1.18至5.80；p = 0.0184）。
我们的研究结果表明，氯吡格雷与阿司匹林联合治疗的血液学不良反应可能比阿司匹林单药治疗更大。
