Casella Gianni, Ottani Filippo, Pavesi Pier Camillo, Sangiorgio Pietro, Rubboli Andrea, Galvani Marcello, Fontanelli Alessandro, Bracchetti Daniele
Cardiology Division, Maggiore Hospital, Bologna, Italy.
Ital Heart J. 2003 Oct;4(10):677-84.
Combination therapy with aspirin plus ticlopidine has become the reference antithrombotic therapy after coronary stenting. However despite its effectiveness, ticlopidine is associated with a significant incidence of severe side effects. Thus, clopidogrel, a ticlopidine analogue with an excellent safety profile, has been introduced in clinical practice. To date only a few, underpowered studies comparing the clinical efficacy of clopidogrel and aspirin versus standard combination therapy after coronary stenting have been performed and the odds ratios (OR) vary substantially among them. The purpose of the present investigation was to update the data regarding this issue by means of a formal meta-analysis.
Ten studies were considered suitable for analysis. The OR were calculated for 30 days of follow-up in patients who had undergone successful coronary stenting. Primary endpoints were a composite of death and non-fatal myocardial infarction (MI) (efficacy endpoint) as well as a composite of major adverse side effects (safety endpoint) as considered in every single study. Secondary endpoints were a composite of major adverse cardiac events, according to single study definition, and individual cardiac events as well.
Overall, 11688 patients were included. At 30 days, the OR for death and non-fatal MI was 0.63 (95% confidence interval-CI 0.47 to 0.85, p = 0.003) in favor of patients treated with clopidogrel and aspirin. There was also a trend toward less major adverse cardiac events (OR 0.83, 95% CI 0.66 to 1.03, p = 0.1), less mortality (OR 0.70, 95% CI 0.40 to 1.25, p = 0.2), and less non-fatal MI (OR 0.76, 95% CI 0.54 to 1.07, p = 0.1). Furthermore, OR for major adverse side effects was 0.53 (95% CI 0.42 to 0.66, p < 0.00001) in favor of clopidogrel. Similarly, drug intolerance was significantly reduced by clopidogrel (OR 0.51, 95% CI 0.36 to 0.72, p < 0.0001). Fewer patients on clopidogrel developed neutropenia or thrombocytopenia (OR 0.58, 95% CI 0.18 to 1.81, p = 0.3), while the incidence of severe bleeding was similar in the two groups (OR 1.19, 95% CI 0.71 to 1.99, p = 0.5).
The present meta-analysis demonstrates that clopidogrel reduces the 30-day combined endpoint of death and non-fatal MI, thereby showing a superior clinical efficacy compared to ticlopidine in patients who had undergone successful coronary stenting. A significantly better safety profile than ticlopidine was also reported, confirming on a larger scale the findings of randomized comparative trials.
阿司匹林联合噻氯匹定的联合疗法已成为冠状动脉支架置入术后的标准抗栓治疗方法。然而，尽管噻氯匹定疗效显著，但与严重副作用的高发生率相关。因此，氯吡格雷这种具有出色安全性的噻氯匹定类似物已被应用于临床实践。迄今为止，仅有少数样本量不足的研究比较了冠状动脉支架置入术后氯吡格雷与阿司匹林联合治疗和标准联合治疗的临床疗效，且这些研究中的优势比（OR）差异很大。本研究的目的是通过正式的荟萃分析更新关于此问题的数据。
十项研究被认为适合进行分析。计算成功进行冠状动脉支架置入术患者30天随访期的OR。主要终点是每项研究中所考虑的死亡与非致命性心肌梗死（MI）的复合终点（疗效终点）以及主要不良副作用的复合终点（安全终点）。次要终点是根据单项研究定义的主要不良心脏事件的复合终点以及个体心脏事件。
总体而言，共纳入11688例患者。在30天时，接受氯吡格雷和阿司匹林治疗的患者死亡与非致命性MI的OR为0.63（95%置信区间[CI]0.47至0.85，p = 0.003）。在主要不良心脏事件方面也有减少趋势（OR 0.83，95%CI 0.66至1.03，p = 0.１），死亡率降低（OR 0.70，95%CI 0.40至1.25，p = 0.2），非致命性MI减少（OR 0.76，95%CI 0.54至1.07，p = 0.1）。此外，主要不良副作用的OR为0.53（95%CI 0.42至0.66，p < 0.00001），支持氯吡格雷。同样，氯吡格雷显著降低了药物不耐受性（OR 0.51，95%CI 0.36至0.72，p < 0.0001）。服用氯吡格雷的患者发生中性粒细胞减少或血小板减少的较少（OR 0.58，95%CI 0.18至1.81，p = 0.3），而两组严重出血的发生率相似（OR 1.19，95%CI 0.71至1.99，p = 0.5）。
本荟萃分析表明氯吡格雷降低了30天死亡与非致命性MI的联合终点，从而在成功进行冠状动脉支架置入术的患者中显示出比噻氯匹定更优的临床疗效。还报告了氯吡格雷的安全性显著优于噻氯匹定，在更大规模上证实了随机对照试验的结果。
