Valgimigli Marco, Campo Gianluca, de Cesare Nicoletta, Meliga Emanuele, Vranckx Pascal, Furgieri Alessandro, Angiolillo Dominick J, Sabatè Manel, Hamon Martial, Repetto Alessandra, Colangelo Salvatore, Brugaletta Salvatore, Parrinello Giovanni, Percoco Gianfranco, Ferrari Roberto
Cardiovascular Institute, University of Ferrara, S. Anna Hospital, Corso Giovecca 203, Ferrara, Italy.
Circulation. 2009 Jun 30;119(25):3215-22. doi: 10.1161/CIRCULATIONAHA.108.833236. Epub 2009 Jun 15.
Inhibition of platelet aggregation after aspirin or clopidogrel intake varies greatly among patients, and previous studies have suggested that poor response to oral antiplatelet agents may increase the risk of thrombotic events, especially after coronary angioplasty. Whether this reflects suboptimal platelet inhibition per se, which might benefit from more potent antiplatelet agents such as tirofiban, is unknown.
We screened 1277 patients to enroll 93 aspirin, 147 clopidogrel, and 23 dual poor responders, based on a point-of-care assay, who underwent elective coronary angioplasty at 10 European sites for stable or low-risk unstable coronary artery disease. Patients were randomly assigned in a double-blind manner to receive either tirofiban (n=132) or placebo (n=131) on top of standard aspirin and clopidogrel therapy. The primary end point, consisting of troponin I/T elevation at least 3 times the upper limit of normal, was attained in 20.4% (n=27) in the tirofiban group compared with 35.1% (n=46) in the placebo group (relative risk, 0.58; 95% confidence interval, 0.39 to 0.88; P=0.009). The rate of major adverse cardiovascular events within 30 days in the tirofiban group also was reduced (3.8% versus 10.7%; P=0.031). The overall incidence of bleeding was low, likely explained by a substantial use of the transradial approach, and did not differ between the 2 groups.
In low-risk patients according to clinical presentation who had poor responsiveness to standard oral platelet inhibitors via a point-of-care assay, intensified platelet inhibition with tirofiban lowers the incidence of myocardial infarction after elective coronary intervention.
服用阿司匹林或氯吡格雷后，患者的血小板聚集抑制情况差异很大，既往研究提示，口服抗血小板药物反应不佳可能会增加血栓形成事件的风险，尤其是在冠状动脉血管成形术后。这是否反映了血小板抑制本身未达最佳状态，而这种情况可能会从替罗非班等更强效的抗血小板药物中获益，目前尚不清楚。
我们对1277例患者进行了筛查，根据即时检验结果，选取了93例对阿司匹林反应不佳、147例对氯吡格雷反应不佳以及23例对两者均反应不佳的患者，这些患者在欧洲10个地点因稳定型或低风险不稳定型冠状动脉疾病接受择期冠状动脉血管成形术。患者以双盲方式随机分配，在标准阿司匹林和氯吡格雷治疗基础上，接受替罗非班（n = 132）或安慰剂（n = 131）治疗。替罗非班组主要终点事件（肌钙蛋白I/T升高至少3倍正常上限）的发生率为20.4%（n = 27），而安慰剂组为35.1%（n = 46）（相对风险，0.58；95%置信区间，0.39至0.88；P = 0.009）。替罗非班组30天内主要不良心血管事件发生率也有所降低（3.8%对10.7%；P = 0.031）。出血总体发生率较低，可能是因为大量采用了经桡动脉途径，两组之间无差异。
对于临床表现为低风险且通过即时检验对标准口服血小板抑制剂反应不佳的患者，使用替罗非班强化血小板抑制可降低择期冠状动脉介入治疗后心肌梗死的发生率。
